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Sample records for experimental verapamil induced

  1. Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

    Science.gov (United States)

    Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

    2018-05-03

    People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

  2. Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

    Science.gov (United States)

    Bhatt, Parloop A; Makwana, Dharmesh

    2008-02-01

    The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

  3. Verapamil stereoisomers induce antiproliferative effects in vascular smooth muscle cells via autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Salabei, Joshua K. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States); Balakumaran, Arun [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Frey, Justin C. [Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Boor, Paul J. [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Treinen-Moslen, Mary [Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555‐0609 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202 (United States); Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States)

    2012-08-01

    Calcium channel blockers (CCBs) are important in the management of hypertension and limit restenosis. Although CCB efficacy could derive from decreased blood pressure, other mechanisms independent of CCB activity also can contribute to antiproliferative action. To understand mechanisms of CCB-mediated antiproliferation, we studied two structurally dissimilar CCBs, diltiazem and verapamil, in cultured rat vascular smooth muscle cells (VSMC). To elucidate CCB-independent effects, pure stereoisomers of verapamil (R-verapamil, inactive VR; S-verapamil, active, VS) were used. The effects of CCB exposure on cell viability (MTT reduction), cell proliferation ({sup 3}H-thymidine incorporation), VSMC morphology by light and transmission electron microscopy (TEM) and autophagy (LC3I/II, ATG5) were measured. In general, verapamil, VR or VS treatment alone (80 μM) appreciably enhanced MTT absorbance although higher concentrations (VR or VS) slightly decreased MTT absorbance. Diltiazem (140 μM) markedly decreased MTT absorbance (40%) at 120 h. VR or VS treatment inhibited {sup 3}H-thymidine incorporation (24 h) and induced cytological alterations (i.e., karyokinesis, enhanced perinuclear MTT deposition, accumulated perinuclear “vacuoles”). TEM revealed perinuclear “vacuoles” to be aggregates of highly laminated and electron-dense vesicles resembling autophagosomes and lysosomes, respectively. Increased autophagosome activity was confirmed by a concentration-dependent increase in LC3-II formation by Western blotting and by increased perinuclear LC3-GFP{sup +} puncta in verapamil-treated VSMC. Verapamil stereoisomers appeared to decrease perinuclear mitochondrial density. These observations indicate that antiproliferative effects of verapamil stereoisomers are produced by enhanced mitochondrial damage and upregulated autophagy in VSMC. These effects are independent of CCB activity indicating a distinct mechanism of action that could be targeted for more efficacious anti

  4. INTERACTION OF VERAPAMIL AND LITHIUM AT THE NEUROMUSCULAR JUNCTION ON RAT ISOLATED MUSCLE-HEMIDIAPHRAGM

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    H. R. Sadeghipour

    1998-08-01

    Full Text Available It has been reported that cither lithium or verapamil can potentiate the neuromuscular blocking activity of certain neuromuscular blockers. In the present investigation, possible interaction of verapamil with lithium has been described. The dose ■ response effects of verapamil and lithium on diaphragmatic contractility were assessed in vitro. Mechanical responses of the muscle to indirect (nerve and direct (muscle electrical stimulation were recorded. Verapamil depressed rat diaphragm twitch tensions induced by nerve stimulation in a dose - dependent manner with the 50 percent depression of the original twitch tensions (ICSQ by 5.6 xlO^mmol/l."nThe IC50 of verapamil for direct stimulation of the muscle was LI x W'5 mmol II. Partial replacement of sodium chloride by lithium chloride (0.5, 1.5 and 5 mmol /1 in the medium did not change the depressant effect of verapamil on muscle twitches induced by direct (muscle or indirect (nerve electrical stimulation.

  5. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals.

    Science.gov (United States)

    Khakzad, Mohammad Reza; Mirsadraee, Majid; Mohammadpour, Amirhooshang; Ghafarzadegan, Kamram; Hadi, Raziye; Saghari, Mahdiye; Meshkat, Mojtaba

    2012-04-01

    Goblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice. Male BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale. Inflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57±1.30% for low dose; 1.50±0.93% for high dose versus 12.93±7.55%, Pcells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45±0.30 for low dose; 0.81±1.00 for high dose versus 2.85±0.86 in the sensitized control group, P<0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized

  6. Verapamil-induced breakdown of the blood-brain barrier presenting as a transient right middle cerebral artery syndrome.

    Science.gov (United States)

    Pace, Jonathan; Nelson, Jeffrey; Ray, Abhishek; Hu, Yin

    2017-12-01

    A middle-aged patient presented for elective embolization of an incidentally found right internal carotid aneurysm. An angiogram was performed, during which the left internal carotid artery was visualized to evaluate a second, small aneurysm. During the embolization of the right internal carotid artery aneurysm, a catheter-induced vasospasm was identified that prompted treatment with intra-arterial verapamil. The procedure was uncomplicated; a postoperative rotational flat-panel computed tomography scan was performed on the angiography table that demonstrated right hemisphere contrast staining. The patient developed a right middle cerebral artery (MCA) syndrome after extubation with repeat cerebral angiography negative for occlusion and magnetic resonance imaging negative for stroke. The patient was observed for 48 hours, during which time the patient had slowly improved. At a six-week follow up visit, the patient had fully recovered. We present an interesting case of a verapamil-induced breakdown of the blood-brain barrier and self-limited right MCA syndrome.

  7. Effect of verapamil on heart rate variability after an acute myocardial infarction. Danish Verapamil Infarction Trial II

    DEFF Research Database (Denmark)

    Vaage-Nilsen, M; Rasmussen, Verner

    1998-01-01

    with verapamil significantly reduced sudden death, the aim of the present substudy was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain, measured in two 5-minute segments during the day and night. Thirty-eight patients were examined by Holter monitoring, at 1 week......-16 months of treatment. In accord with the known reduction of overall heart rate by verapamil, a significant increase of mean NN interval from before to after 1 (P = 0.0004) and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in the placebo, group at night. Parameters generally......, the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfarction period....

  8. Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

    International Nuclear Information System (INIS)

    Perna, A.F.; Smogorzewski, M.; Massry, S.G.

    1988-01-01

    Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

  9. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

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    Su Xue-Feng

    2010-05-01

    Full Text Available Abstract Background Lung epithelial Na+ channels (ENaC are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441, and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P Ca3.1 (1-EBIO and KATP (minoxidil channel openers significantly recovered AFC. In addition to short-circuit current (Isc in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na, K Ca3.1 (1-EBIO, and KATP (minoxidil channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal.

  10. A study on the action of two calcium channel blockers (verapamil and flunarizine upon an experimental model of tardive dyskinesia in rats

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    João S. Pereira

    1992-09-01

    Full Text Available Tardive dyskinesia (TD, a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphyne was rated. The CCB drugs were administered in acute (in the 28th. day and chronic (for 8 days, after the 25th day experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD.

  11. EFFECTS OF VERAPAMIL ON CHICKEN BIVENTER - CERVICIS MUSCLE

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    F.Farokhy

    1999-06-01

    Full Text Available - Verapamil produces a sustained contraction in isolated biventer-cervicis muscle of chickens between 2-8 days old. From cumulative dose-response curves, ED50 of was calculated for this effect of verapamil. when isolated chicken biventer-cervicis muscle was electrically stimulated, verapamil had no effect on twitch contractures but increased the base line tone of the muscle. Glycerol treatment of the muscle reduced the responses to acetylcholine and KCl but had little effect on contracture produced by verapamil, and no effect on contracture produced by caffeine. Incubation of the muscles with calcium-free Krcbs solution omitted the responses of the muscle to acetylcholine and reduced the response to caffeine. Again, the responses to caffeine and verapamil were less affected compared to KCL. Addition of ethylene glycol tetra-acetic acid (EGTA (2.5 mM abolished the responses of muscle to all compounds. It was concluded that verapamil produces contracture of the muscle by release of calcium from intracellular stores.

  12. Differential antiepileptic effects of the organic calcium antagonists verapamil and flunarizine in neurons of organotypic neocortical explants from newborn rats

    NARCIS (Netherlands)

    Bingmann, D; Speckmann, E J; Baker, R E; Ruijter, J; de Jong, B. M.

    1988-01-01

    Effects of the organic calcium antagonists verapamil and flunarizine on pentylenetetrazol induced paroxysmal depolarizations were tested in organotypic neocortical explants taken from neonatal rats. In these in vitro experiments the papaverin derivative verapamil depressed, and finally abolished,

  13. Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients

    International Nuclear Information System (INIS)

    Abrahim, Aiman; Langer, Oliver; Luurtsema, Gert; Lubberink, Mark; Lammertsma, Adriaan A.; Bauer, Martin; Joukhadar, Christian; Mueller, Markus; Karch, Rudolf; Pataraia, Ekaterina; Baumgartner, Christoph; Kletter, Kurt

    2008-01-01

    (R)-[ 11 C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[ 11 C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[ 11 C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. Arterial blood samples were collected from eight patients undergoing (R)-[ 11 C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[ 11 C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. Peripheral metabolism of (R)-[ 11 C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[ 11 C]verapamil fraction in plasma: 29.4 ± 3.9 min for patients versus 40.8 ± 5.0 min for healthy volunteers; p 11 C]verapamil plasma concentrations (AUC of (R)-[ 11 C]verapamil concentration, normalised to injected dose per body weight: 25.5 ± 2.1 min for patients and 30.5 ± 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [ 11 C]metabolite fraction was up to two-fold greater in patients. Faster metabolism of (R)-[ 11 C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. (orig.)

  14. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...

  15. Pharmaceutical Factors Affecting The Formulation Of Verapamil HCl ...

    African Journals Online (AJOL)

    Floating sustained release Verapamil HCl capsules were prepared using different polymers. Hydroxypropylmethyl cellulose 4000 and 50 (HPMC 4000 & HPMC 50), Carbopol 934, sodium alginate (Na alginate), carboxymethyl cellulose (CMC) and Pectin were used to study their effect on the release of Verapamil HCl from ...

  16. 15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats.

    Science.gov (United States)

    Moustafa, Y M; El-Azab, M F; Fouda, A

    2013-01-01

    15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme responsible for prostaglandins (PGs) metabolism. PGs have an important role in the protection of stomach mucosa against destructive stimuli. The aim of the present study is to investigate the inhibitory effect of carbenoxolone, pioglitazone and verapamil on 15-PGDH enzyme. The experiments were carried out in the Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.), except for the negative control group which received saline only, followed by pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30 mg/kg) or their combinations 30 minutes before indomethacin. The rats were sacrificed after four hours of pyloric ligation. The effects of the previous treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa, the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme activity were determined. Indomethacin resulted in severe ulceration and increased gastric acid output (p ulcer index, gastric acid output and 15-PGDH activity (p ulcer index, gastric acid output and 15-PGDH activity (p stomach mucosa.

  17. Peripheral metabolism of (R)-[{sup 11}C]verapamil in epilepsy patients

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    Abrahim, Aiman; Langer, Oliver [Medical University of Vienna, Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna (Austria); Austrian Research Centers GmbH - ARC, Department of Radiopharmaceuticals, Seibersdorf (Austria); Luurtsema, Gert; Lubberink, Mark; Lammertsma, Adriaan A. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Bauer, Martin; Joukhadar, Christian; Mueller, Markus [Medical University of Vienna, Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna (Austria); Karch, Rudolf [Medical University of Vienna, Department of Medical Computer Sciences, Vienna (Austria); Pataraia, Ekaterina; Baumgartner, Christoph [Medical University of Vienna, Department of Neurology, Vienna (Austria); Kletter, Kurt [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria)

    2008-01-15

    (R)-[{sup 11}C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R)-[{sup 11}C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R)-[{sup 11}C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. Arterial blood samples were collected from eight patients undergoing (R)-[{sup 11}C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[{sup 11}C]verapamil by using an assay that measures polar N-demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. Peripheral metabolism of (R)-[{sup 11}C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R)-[{sup 11}C]verapamil fraction in plasma: 29.4 {+-} 3.9 min for patients versus 40.8 {+-} 5.0 min for healthy volunteers; p < 0.0005, Student's t-test), which resulted in lower (R)-[{sup 11}C]verapamil plasma concentrations (AUC of (R)-[{sup 11}C]verapamil concentration, normalised to injected dose per body weight: 25.5 {+-} 2.1 min for patients and 30.5 {+-} 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [{sup 11}C]metabolite fraction was up to two-fold greater in patients. Faster metabolism of (R)-[{sup 11}C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. (orig.)

  18. MICROMORPHOLOGICALCHARACTERISTICS OF THE LIVER AND BIOCHEMICAL ANALYSES IN THE BLOOD OF RATS TREATED BY GENTAMICIN AND VERAPAMIL

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    Milan Stoiljkovic

    2006-04-01

    Full Text Available The use of antimicrobial drugs, especially gentamicin and calcium blocker verapamil, may cause transitional functional damage of the liver.The aim of this study is to explore micro-morphological changes in the liver and biochemical changes in the blood of rats treated with gentamicin and verapamil. The research included 20 rats divided in experimental and control group. The experimental group (10 rats was treated with gentamicin (100 mg/kg/BW/24h and verapamil (3 mg/kgBW/24 h for 8 days. The control group (10 rats received physiological solution (1 ml/kgBW/24 h at the same time. We analyzed micro-morphological changes in the liver and biochemical parameters in blood: transaminase, bilirubin and glucose.In the control group, there was a normal lobular liver structure. All hepatocytes had polygonal shape, pink cytoplasm and the location of nucleus was central or paracentral. Biochemical blood analysis showed normal level of transaminase (SGOT 29.5 +/- 7.4 iu/l; SGPT 31.7 +/- 6.9 iu/l, total bilirubin (3.1 +/- 0.9 mmol/l and glucose (4.9 +/- 0.9 mmol/l. In the experimental group of animals, hepatocytes of all three zones were equally damaged. In the cytoplasm, we found vacuolar degeneration, reduced condensation of chromatine in nucleus and light nucleoplasm. Hepatocytes of the periportal zone had acidofillic degeneration, picnotic and hiperchromatic nuclei. Biochemical blood analysis showed high level of transaminase (SGOT 46.4 +/- 4.7 iu/l; SGPT 50.8+/-6.1 iu/l, total bilirubin (12.8+/-1.7 mmol/l and glucose (9.3+/-1.8 mmol/l. There is a statistically significant difference in biochemical parameters between the two groups (p < 0,001. The results of our experimental study suggest that there is an obvious correlation between application of gentamicin and verapamil and these changes.

  19. Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy.

    Science.gov (United States)

    Iannetti, Paola; Parisi, Pasquale; Spalice, Alberto; Ruggieri, Martino; Zara, Federico

    2009-07-01

    We report on the use of the voltage-gated calcium channel blocker (Vg-CCB), verapamil, as an add-on anticonvulsant medication in two girls, 4 and 14 years of age, who were affected by severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome, a channelopathy caused by abnormalities in the voltage-gated sodium channel neuronal type alpha1 subunit (SCN1A) gene at 2q24. Both girls had pharmacoresistant epilepsy and developmental delay. Mutation analysis for the SCN1A gene revealed a missense mutation in exon 2 in the 4-year-old girl. Verapamil was co-administered in both children with a prompt response in controlling status epilepticus, myoclonic jerks, and partial and generalized seizures. The therapeutic effect lasted 13 months in the 14-year-old girl, while it is still present after a 20-month follow-up period in the 4-year-old girl who, in addition, has experienced improvement in motor and language development. The verapamil vVg-CCB, which crosses the blood-brain barrier (BBB): (a) inhibits the P-glycoprotein, an active efflux transporter protein expressed in normal tissue, including the brain, which is believed to contribute to the in situ phenomenon of multidrug resistance; and (b) may regulate membrane depolarization induced by abnormal sodium channels functions by modulating the abnormal Ca++ influxes into neurons with subsequent cell resting. This is the first report on long-lasting verapamil therapy in SMEI. The functional consequences of such in vivo modulating effects on Ca++ channels could contribute to rational targeting for future molecular therapeutic approaches in pharmacoresistant epileptic channelopathies.

  20. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

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    Bankstahl, Jens P; Kuntner, Claudia; Abrahim, Aiman; Karch, Rudolf; Stanek, Johann; Wanek, Thomas; Wadsak, Wolfgang; Kletter, Kurt; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

    2008-08-01

    The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.

  1. Direct interaction between verapamil and doxorubicin causes the lack of reversal effect of verapamil on P-glycoprotein mediated resistance to doxorubicin in vitro using L1210/VCR cells

    International Nuclear Information System (INIS)

    Breier, A.; Drobna, Z.; Barancik, M.

    1998-01-01

    Mouse leukemic cell sub-line L 1210/VCR exerts expressive multidrug resistance (MDR) that is mediated by P-glycoprotein. Cells originally adapted to vincristine are also extremely resistant to doxorubicin. Resistance to both vincristine and doxorubicin is connected with depression of drug uptake. While resistance of L 121 O cells to vincristine could be reversed by verapamil as chemo-sensitizer, resistance of cells to doxorubicin was insensitive to verapamil. Action of verapamil (well-known inhibitor of PGP activity) on multidrug resistance was often used as evidence that MDR is mediated by PGP. From this point it may be possible that the resistance of L1210/VCR cells to vincristine is mediated by PGP and the resistance to doxorubicin is mediated by other PGP-independent system. Another and more probable explanation of different effect of verapamil on resistance of L1210/VCR cells to vincristine and doxorubicin may be deduced from the following fact: Using UV spectroscopy we found that doxorubicin dissolved in water buffered medium interacts effectively with verapamil. This interaction may be responsible for the decrease of concentration of both drugs in free effective form and consequently for higher survival of cells. In contrast to doxorubicin vincristine does not give any interaction with verapamil that is measurable by UV spectroscopy and resistance of L1210/VCR cells to vincristine may be fully reversed by verapamil. (authors)

  2. A prospective, randomized, single - blind study comparing intraplaque injection of thiocolchicine and verapamil in Peyronie's Disease: a pilot study

    Directory of Open Access Journals (Sweden)

    I. L. Toscano Jr.

    Full Text Available ABSTRACT Objectives: To compare the response to tiocolchicine and verapamil injection in the plaque of patients with Peyronie's disease. Materials and Methods: Prospective, single-blind, randomized study, selecting patients who have presented Peyronie's disease for less than 18 months. Thiocolchicine 4mg or verapamil 5mg were given in 7 injections (once a week. Patients who had received any treatment for Peyronie's disease in the past three months were excluded. The parameters used were the International Index of Erectile Function (IIEF-5 score, analysis of the curvature on pharmaco-induced erections and size of the plaque by ultrasonography. Results: Twenty-five patients were randomized, 13 received thiocolchicine and 12 were treated with verapamil. Both groups were statistically similar. The mean curvature was 46.7° and 36.2° before and after thiocolchicine, respectively (p=0.019 and 50.4° and 42.08° before and after verapamil, respectively (p=0.012. The curvature improved in 69% of patients treated with thiocolchicine and in 66% of those who received verapamil. Regarding sexual function, there was an increase in the IIEF-5 from 16.69 to 20.85 (p=0.23 in the thiocolchicine group. In the verapamil group the IIEF-5 score dropped from 17.50 to 16.25 (p=0.58. In the thiocolchicine group, the plaque was reduced in 61% of patients. In the verapamil group, 8% presented decreased plaque size. No adverse event was associated to thiocolchicine. Conclusion: The use of thiocolchicine in Peyronie's disease demonstrated improvement on penile curvature and reduction in plaque size. Thiocolchicine presented similar results to verapamil in curvature assessment. No significant side effects were observed with the use of tiocolchicine.

  3. Analgesia Synergism of Essential Oil from Pericarp of Zanthoxylum schinifolium and Verapamil

    Directory of Open Access Journals (Sweden)

    Gao Wu

    2014-01-01

    Full Text Available Objective. To evaluate the synergistic analgesic effect of essential oil of Zanthoxylum schinifolium Sieb. et Zucc. (EOZ and verapamil (Ver. Method. The qualitative and quantitative composition of EOZ were determined with gas chromatography/Mass spectrometer. The interaction between EOZ and Ver in antinociceptive activity was evaluated by using acetic acid-induced writhing, hot plate, and tail flick tests in mice and in isolated toad sciatic nerve test. Results. Linalool, limonene, and sabinene are the major components of EOZ. EOZ (middle-dose: 40 mg·kg−1, high-dose: 80 mg·kg−1 and EOZ + Ver (Each dose group have remarkable analgesic effects on pain in mice induced by acetic acid-induced writhing, hot plate, and tail flick tests. Low-dose EOZ (20 mg·kg−1 had no analgesic action, but when it is combined with Ver it has shown significant antinociception. Verapamil has a faint analgesic effect but was not able to inhibit action potential transmission in toad sciatic nerve. EOZ (0.2% and EOZ + Ver (0.2% + 0.05% also inhibited action potential transmission in toad sciatic nerve. Combination of EOZ with Ver had a greater analgesic effect and inhibition of nerve action potential transmission compared to its components EOZ and Ver. Conclusion. The combination of EOZ with Ver produces a synergistic analgesic effect.

  4. (R-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Lammertsma Adriaan A

    2011-01-01

    Full Text Available Abstract Background Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp expression and functionality at an early stage after induction of status epilepticus by kainate. Methods (R-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles as well as by population mixed effects modelling (NONMEM. Results All data analysis approaches indicated only modest differences in brain distribution of (R-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. Conclusions P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

  5. (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    International Nuclear Information System (INIS)

    Syvänen, Stina; Luurtsema, Gert; Molthoff, Carla FM; Windhorst, Albert D; Huisman, Marc C; Lammertsma, Adriaan A; Voskuyl, Rob A; Lange, Elizabeth C de

    2011-01-01

    Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate. (R)-[ 11 C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[ 11 C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[ 11 C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM). All data analysis approaches indicated only modest differences in brain distribution of (R)-[ 11 C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate

  6. Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

    Science.gov (United States)

    ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

    2016-01-01

    Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

  7. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  8. (R)-[{sup 11}C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Syvänen, Stina [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands); Luurtsema, Gert [Department of Nuclear Medicine & Molecular Imaging, Groningen University Medical Center, P.O. Box 30.001 9700 RB Groningen (Netherlands); Molthoff, Carla FM; Windhorst, Albert D; Huisman, Marc C; Lammertsma, Adriaan A [Department of Nuclear Medicine & PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam (Netherlands); Voskuyl, Rob A [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands); Epilepsy Institute of The Netherlands Foundation (SEIN), P.O. Box 21, 2100 AA, Heemstede (Netherlands); Lange, Elizabeth C de [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands)

    2011-01-03

    Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate. (R)-[{sup 11}C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[{sup 11}C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[{sup 11}C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM). All data analysis approaches indicated only modest differences in brain distribution of (R)-[{sup 11}C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

  9. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, Christoph, E-mail: steinbach@frov.jcu.cz [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Fedorova, Ganna [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic); Prokes, Miroslav [Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., Kvetna 8, 603 65 Brno (Czech Republic); Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour [Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, CZ-38925 Vodnany (Czech Republic)

    2013-09-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L{sup −1} to μg L{sup −1}. In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC{sub 50} values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L{sup −1} for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L{sup −1}. Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L{sup −1} of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of

  10. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    International Nuclear Information System (INIS)

    Steinbach, Christoph; Fedorova, Ganna; Prokes, Miroslav; Grabicova, Katerina; Machova, Jana; Grabic, Roman; Valentova, Olga; Kroupova, Hana Kocour

    2013-01-01

    Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L −1 to μg L −1 . In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC 50 values of verapamil were estimated at 16.4 ± 9.2, 7.3 ± 1.5 and 4.8 ± 0.2 mg L −1 for embryos (E5–E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 μg L −1 . Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 μg L −1 of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF > 500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2 ± 1.6 days and 44.2 ± 8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations. - Highlights: • Study of the acute and sub-chronic toxicity of verapamil on early-life stages of common carp. • Acute exposure to verapamil reduced the heart rate in early-life stages of common carp. • The

  11. Successful usage of intravenous lipid emulsion in treatment of acute verapamil poisoning: A case report

    Directory of Open Access Journals (Sweden)

    Vuković-Ercegović Gordana

    2017-01-01

    Full Text Available Introduction. During the last few years, intravenous lipid emulsions have been effectively used in treatment of acute poisonings with lipophilic substances, including verapamil. Case report. A 37-year-old women presented 1 hour after ingestion of 2.8 g verapamil with hypotension and complete heart block. Because of the applied standard therapy failure and further patients impairment, Intralipid® 20% was used. Sinus rhythm was restored, arterial blood pressure increased and verapamile concentrations, both total and free decreased. Conclusion. Intravenous lipid emulsion can be important in treatment of severe acute intoxication and cardiotoxicity caused by verapamil.

  12. Treatment of out-of-hospital supraventricular tachycardia: adenosine vs verapamil.

    Science.gov (United States)

    Brady, W J; DeBehnke, D J; Wickman, L L; Lindbeck, G

    1996-06-01

    To compare the use of adenosine and the use of verapamil as out-of-hospital therapy for supraventricular tachycardia (SVT). A period of prospective adenosine use (March 1993 to February 1994) was compared with a historical control period of verapamil use (March 1990 to February 1991) for SVT. Data were obtained for SVT patients treated in a metropolitan, fire-department-based paramedic system serving a population of approximately 1 million persons. Standard drug protocols were used and patient outcomes (i.e., conversion rates, complications, and recurrences) were monitored. During the adenosine treatment period, 105 patients had SVT; 87 (83%) received adenosine, of whom 60 (69%) converted to a sinus rhythm (SR). Vagal maneuvers (VM) resulted in restoration of SR in 8 patients (7.6%). Some patients received adenosine for non-SVT rhythms: 7 sinus tachycardia, 18 atrial fibrilation, 7 wide-complex tachycardia (WCT), and 2 ventricular tachycardia; no non-SVT rhythm converted to SR and none of these patients experienced an adverse effect. Twenty-five patients were hemodynamically unstable (systolic blood pressure fibrillation). Recurrence of SVT was noted in 2 adenosine patients and 2 verapamil patients in the out-of-hospital setting and in 23 adenosine patients and 15 verapamil patients after ED arrival, necessitating additional therapy (p = 0.48 and 0.88, for recurrence rates and types of additional therapies, respectively). Hospital diagnoses, outcomes, and ED dispositions were similar for the 2 groups. Adenosine and verapamil were equally successful in converting out-of-hospital SVT in patients with similar etiologies responsible for the SVT. Recurrence of SVT occurred at similar rates for the 2 medications. Rhythm misidentification remains a common issue in out-of-hospital cardiac care in this emergency medical services system.

  13. Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report.

    Science.gov (United States)

    Lambert Kuhn, E; Levêque, D; Lioure, B; Gourieux, B; Bilbault, P

    2016-02-01

    Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril. Ibrutinib was discontinued for 5 days, and verapamil was stopped. Lercanidipine 10 mg daily was prescribed as an alternative antihypertensive drug. The patient was discharged after 3 days with symptomatic treatment for his diarrhoea. Three months later, the patient maintained control with ibrutinib and olmesartan, but without verapamil. This is the first description of a serious side effect of ibrutinib likely due to an interaction with the CYP3A4 inhibitor verapamil. Prescriptions of ibrutinib must be carefully checked to identify possible interactions with CYP3A4 inhibitors and patients monitored accordingly. © 2016 John Wiley & Sons Ltd.

  14. Requirements for drug monitoring of verapamil: experience from an unselected group of patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Husum, D; Johnsen, A; Jensen, Gorm Boje

    1990-01-01

    variation (variation coefficient 35.8, 1.9, and 7.4, at the dosage levels 120, 240 and 340 mg per day). No significant correlation was found between serum verapamil levels age, sex, or weight. No significant effect of digoxin on the concentration of serum verapamil was found. No relation was observed...... 620 and D 617 indicated saturation of the first-pass metabolism. In conclusion, therapeutic drug monitoring is not indicated during routine verapamil treatment, whereas single measurements of verapamil may be warranted in patients not responding to treatment in order to identify fast metabolizers...

  15. Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy

    DEFF Research Database (Denmark)

    Nicita, Francesco; Spalice, Alberto; Papetti, Laura

    2014-01-01

    Verapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy....

  16. Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate.

    Science.gov (United States)

    Kaur, Monika; Ita, Kevin B; Popova, Inna E; Parikh, Sanjai J; Bair, Daniel A

    2014-02-01

    The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm(2)/h to 49.96μg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm(2)/h. Passive flux for the drug was 1.57μg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm(2)/h in comparison with passive diffusion flux of 0.19μg/cm(2)/h. The difference in flux values was also statistically significant. Stainless

  17. Sustained release of verapamil hydrochloride from sodium alginate microcapsules.

    Science.gov (United States)

    Farhana, S Ayesha; Shantakumar, S M; Shyale, Somashekar; Shalam, Md; Narasu, Laxmi

    2010-04-01

    The objective of the present study was to develop sustained release microcapsules of verapamil hydrochloride (VH) using biodegradable polymers. For this purpose microcapsules embedded verapamil hydrochloride were prepared using sodium alginate alone and also by incorporating some co polymers like methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC) , poly vinyl pyrollidone (PVP) and xanthan gum by employing complex emulsion method of microencapsulation. Microcapsules were prepared in various core: coat ratios to know the effect of polymer and co polymers on drug release. Overall ten formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy and DSC. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between Verapamil hydrochloride (VH), sodium alginate and between the copolymers. Among the four copolymers used methyl cellulose retarded the drug release more than the other three, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed by using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were almost same. From the study it was concluded that, sustained release Verapamil hydro chloride microcapsules could be achieved with success using sodium alginate alone and also in combination with other biodegradable polymers.

  18. INTRALESIONAL VERAPAMIL INJECTION IN TREATMENT OF

    African Journals Online (AJOL)

    Patients and Methods Twenty-six patients with Peyronie's disease were divided into two groups: the verapamil treatment group. (study group) including 13 patients and the saline group (control group) including an- other 13 patients. The patients' age ranged from 35 to 58 years with a mean age of. 43.75 years. The patients ...

  19. Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Li ZN

    2016-11-01

    Full Text Available Zhouna Li, Zhehu Jin Department of Dermatology, Yanbian University Affiliated hospital, Yanji, Jilin, People’s Republic of China Background: Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars.Methods: Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis.Results: Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil and 53.18% (nonverapamil, respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions.Conclusion: There were no differences between the application of verapamil and nonverapamil group in keloids and

  20. Effect of verapamil on cellular uptake of Tc-99m MIBI and tetrofosmin on several cancer cells

    International Nuclear Information System (INIS)

    Kim, Dae Hyun; Yoo, Jung Ah; Bae, Jin Ho; Jeong, Shin Young; Suh, Myung Rang; Ahn, Byeong Cheol; Lee, Kyu Bo; Lee, Jae Tae

    2004-01-01

    Cellular uptake of 99 mTc-sestamibi (MIBI) and 99 mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 μM at 1*10 6 cells/ m l at 37.deg.C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of 100 μM and the maximal increase at 50 μM was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7m SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 μM. With a concentration of 200 μM verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10μM, but were also decreased with verapamil higher than 10μM, resulting 40% and 5% of baseline at 50 μM. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 μM. Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased

  1. ANTIHYPERTENSIVE EFFICACY OF VERAPAMIL PLUS INDAPAMIDE IN PATIENTS WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    E. M. Idrisova

    2008-01-01

    Full Text Available Aim. To study effect of combination of verapamil retard (Isoptinum SR with indapamide retard (Arifon retard on blood pressure (BP level as well as lipid profile, glucose and electrolytes serum level in patients with metabolic syndrome (MS.Material and methods. 20 women of 35-65 y.o. with MS were examined. The combination of verapamil retard and indapamide retard were prescribed to patients during 24 weeks. Ambulatory BP monitoring (ABPM, lipide profile tests, electrolytes and glucose serum level tests were performed in all patients initially and after treatment.Results. Target systolic BP (SBP was achieved in 90% of patients. Target diastolic BP (DBP was achieved in 75% of patients. Drug combination effectively reduced SBP, DBP and pulse BP levels and improved other BP indices. This drug combination did not affect BP profile as well as glucose and electrolytes serum level, lipid profile.Conclusion. High antihypertensive efficacy and metabolic neutrality of verapamil retard and indapamide retard allows to use this combination in patients with MS.

  2. Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis.

    Science.gov (United States)

    Li, Zhouna; Jin, Zhehu

    2016-01-01

    Keloids and hypertrophic scars are the most common types of pathological scarring. Traditionally, keloids have been considered as a result of aberrant wound healing, involving excessive fibroblast participation that is characterized by hyalinized collagen bundles. However, the usefulness of this characterization has been questioned. In recent years, studies have reported the appropriate use of verapamil for keloids and hypertrophic scars. Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was used for literature review, data extraction, and meta-analysis. Treatment groups were divided into verapamil and nonverapamil group. Nonverapamil group includes steroids and intense pulsed light (IPL) therapy. Total effective rates include cure rate and effective rate. Cure: skin lesions were completely flattened, became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient significantly reduced symptoms. Inefficient definition of skin was progression free or became worse. Random-effects model was used for the meta-analysis. Six studies that included 331 patients with keloids and hypertrophic scars were analyzed. Analysis of the total effective rate of skin healing was performed. The total effective rates in the two groups were 54.07% (verapamil) and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was no difference between the two groups. We also compared the adverse reactions between the verapamil treatment group and the steroids treatment group in two studies, and the result indicated that the verapamil group showed less adverse reactions. There were no differences between the application of verapamil and nonverapamil group in keloids and hypertrophic scars treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and hypertrophic scars. A larger number of studies are required to

  3. The structurally novel Ca2+ channel blocker Ro 40-5967, which binds to the [3H] desmethoxyverapamil receptor, is devoid of the negative inotropic effects of verapamil in normal and failing rat hearts

    International Nuclear Information System (INIS)

    Clozel, J.P.; Veniant, M.; Osterrieder, W.

    1990-01-01

    Ro 40-5967 is a structurally novel Ca 2+ channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max +) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions

  4. Circadian variation in the pharmacokinetics of verapamil

    DEFF Research Database (Denmark)

    Jespersen, C M; Frederiksen, M; Hansen, J F

    1989-01-01

    greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h-06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h-22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night...

  5. The acute hemodynamic effects of intravenous verapamil in coronary artery disease. Assessment by equilibrium-gated radionuclide ventriculography

    International Nuclear Information System (INIS)

    Klein, H.O.; Ninio, R.; Oren, V.; Lang, R.; Sareli, P.; DiSegni, E.; David, D.; Guerrero, J.; Kaplinsky, E.

    1983-01-01

    The acute hemodynamic effects of an i.v. bolus of verapamil, 0.1 mg/kg or 0.06-0.075 mg/kg, were examined by serial radionuclide studies in 46 patients with coronary artery disease. In 20 patients with ejection fractions (EFs) greater than 35% (group 1A), verapamil, 0.1 mg/kg given over 1-11/2 minutes, had a biphasic effect: first, a transient decrease in EF accompanied by increased left ventricular (LV) volumes and cardiac output equivalents; then, an overshoot of EF to values above control, accompanied by a decrease in peripheral vascular resistance and a drastic decrease in LV volumes, while cardiac output equivalent remained slightly elevated. In eight patients with EFs less than 35% (group 1B), only the first effect on EF was noted. In 10 patients with EFs greater than 35% (group 2), verapamil, 0.06-0.075 mg/kg, exerted qualitatively similar but milder effects on hemodynamic function. Finally, verapamil, 0.1 mg/kg given more slowly, over 2-21/2 minutes, produced no significant changes in EF or LV volumes in another eight patients (group 3). The acute effects of verapamil are thus both time-related and dose-dependent. They are also related to the baseline functional reserve of the left ventricle. This study documents that verapamil exerts a depressant effect on LV function. However, the transient nature of this depression and the quick recovery to normal or above-normal values indicate that verapamil, in the doses used in this study, is safe to use intravenously in patients with coronary artery disease

  6. Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects

    NARCIS (Netherlands)

    Sevre, K; Lefrandt, JD; Eide, [No Value; Smit, AJ; Rostrup, M

    2001-01-01

    We compared the effects of amlodipine and verapamil slow release on autonomic responses to a 5-min mental arithmetic test (MST) in patients with mild to moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release 240 mg or amlodipine 10 mg in a double-blind crossover design,

  7. Development and evaluation of floating microspheres of verapamil hydrochloride Desenvolvimento e avaliação de microesferas flutuantes de cloridrato de verapamil

    Directory of Open Access Journals (Sweden)

    Yuveraj Singh Tanwar

    2007-12-01

    Full Text Available The present study involves preparation and evaluation of floating microspheres of verapamil hydrochloride for improving the drug bioavailability by prolongation of gastric residence time. Cellulose acetate, acrycoat S100 and eudragit S100 microspheres loaded with verapamil hydrochloride were prepared by solvent diffusion-evaporation method. The microspheres had smooth surfaces, with free-flowing and good-packing properties. The yield of the microspheres was up to 70.51% and cellulose acetate microspheres entrapped the maximum amount of the drug. Scanning electron microscopy confirmed their hollow structures with sizes in the range 251.80 to 350.75 mm. The prepared microspheres exhibited prolonged drug release and remained buoyant for more than 12 h. Radiographic images of dog stomach revealed that cellulose acetate microspheres loaded with barium sulphate floated on the gastric fluid for about 3.2 h. In vitro release studies demonstrated non-Fickian diffusion of drug from the microspheres.O presente estudo envolve a preparação e a avaliação de microesferas flutuantes de cloridrato de verapamil para o melhoramento da biodisponibilidade do fármaco por meio do prolongamento do tempo de residência gástrica. Prepararam-se, por meio do método de difusão-evaporação de solvente, microesferas de acetato de celulose, acrycoat S100 e eudragit S100 carregadas com cloridrato de verapamil. As microesferas apresentaram superfícies regulares, com propriedades de fluxo livre e de bom empacotamento. O rendimento das microesferas foi superior a 70,51% e as microesferas de acetato de celulose captaram a quantidade máxima do fármaco. Microscopia eletrônica de varredura confirmou as cavidades em suas estruturas, com tamanhos na faixa de 251,80 a 350,75 mm. As microesferas preparadas apresentaram liberação prolongada do fármaco e permaneceram flutuantes por mais que 12 h. Imagens radiográficas do estômago de cão revelaram que as esferas de acetato

  8. Enhancement of absorption and bioavailability of echinacoside by verapamil or clove oil

    Directory of Open Access Journals (Sweden)

    Shen JY

    2015-08-01

    Full Text Available Jin-Yang Shen,1,* Xiao-Lin Yang,2,* Zhong-Lin Yang,1 Jun-Ping Kou,1 Fei Li11State Key Laboratory of Natural Medicines, China Pharmaceutical University, 2Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workPurpose: This present study investigated the absorption kinetics of echinacoside (ECH in situ and in vitro and its oral bioavailability in rats. Additional aim was to find an agent(s to promote ECH absorption and oral bioavailability among two efflux proteins and three absorption promoters.Methods: ECH absorption behaviors were investigated by everted gut sac model in vitro and single-pass intestinal perfusion model in situ. Pharmacokinetics study was performed to investigate the influences of verapamil and clove oil on ECH bioavailability in vivo. All samples were measured at different time intervals by high performance liquid chromatography.Results: The results showed that the effective permeability coefficient (Peff and apparent permeability coefficient of ECH were 0.83×10-6–3.23×10-6 cm/s and 2.99×10-6–9.86×10-6 cm/s, respectively. The Peff among duodenum, jejunum, and ileum were not statistically different, but they were higher than colon (P<0.01, which demonstrated that intestinal ECH absorption was poor and site dependent. Additionally, verapamil and clove oil significantly increased the jejunal Peff of ECH both in situ and in vitro. Moreover, the bioavailability of ECH in combination with verapamil and clove oil were increased by 1.37-fold (P<0.05 and 2.36-fold (P<0.001, respectively, when compared to ECH group. Overall, verapamil and clove oil facilitated ECH absorption and oral bioavailability.Conclusion: The absorption and bioavailability of ECH were enhanced by verapamil and clove oil, respectively, both in vitro and in vivo. Consequently

  9. Rapid solid-phase extraction method to quantify [11C]-verapamil, and its [11C]-metabolites, in human and macaque plasma

    International Nuclear Information System (INIS)

    Unadkat, Jashvant D.; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara; Mankoff, David; Collier, Ann C.; Muzi, Mark; Link, Jeanne

    2008-01-01

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [ 11 C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [ 11 C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [ 11 C]-D-617/717. Using sequential and differential pH elution on C 8 SPE cartridges, we developed a rapid method to separate [ 11 C]-verapamil and [ 11 C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [ 11 C], this method provides a valuable tool to rapidly determine the concentration of [ 11 C]-verapamil and its [ 11 C]-metabolites in human and nonhuman primate plasma

  10. Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.

    Science.gov (United States)

    Bonow, R O; Ostrow, H G; Rosing, D R; Cannon, R O; Lipson, L C; Maron, B J; Kent, K M; Bacharach, S L; Green, M V

    1983-11-01

    To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are

  11. Synthesis and preclinical evaluation of [11C]D617, a metabolite of (R)-[11C]verapamil

    NARCIS (Netherlands)

    Verbeek, Joost; Syvänen, Stina; Schuit, Robert C.; Eriksson, Jonas; de Lange, Elizabeth C M; Windhorst, Albert D.; Luurtsema, Gert; Lammertsma, Adriaan A.

    2012-01-01

    OBJECTIVES: (R)-[(11)C]verapamil is widely used as a positron emission tomography (PET) tracer to evaluate P-glycoprotein (P-gp) functionality at the blood-brain barrier in man. A disadvantage of (R)-[(11)C]verapamil is the fact that its main metabolite, [(11)C]D617, also enters the brain. For

  12. Fast dissolving strips: A novel approach for the delivery of verapamil

    Directory of Open Access Journals (Sweden)

    S Kunte

    2010-01-01

    Full Text Available Objective: Fast dissolving drug delivery system offers a solution for those patients having difficulty in swallowing tablets/capsules etc. Verapamil is a calcium channel blocker used as an antianginal, antiarrhythmic, and antihypertensive agent with extensive first pass metabolism which results in less bioavailability. This work investigated the possibility of developing verapamil fast dissolving strips allowing fast, reproducible drug dissolution in the oral cavity; thus bypassing first pass metabolism. Materials and methods: The fast dissolving strips were prepared by solvent casting technique with the help of HPMC E6 and maltodextrin. The strips were evaluated for drug content uniformity, film thickness, folding endurance, in vitro disintegration time, in vitro dissolution studies, surface pH study, and palatability study. Results: Official criteria for evaluation parameters were fulfilled by all formulations. Disintegration time showed by formulations was found to be in range of 20.4-28.6 sec. Based on the evaluation parameters, the formulation containing 2% HPMC E6 and 3.5% maltodextrin showed optimum performance against other formulations. Conclusion: It was concluded that the fast dissolving strips of verapamil can be made by solvent casting technique with enhanced dissolution rate, taste masking, and hence better patient compliance and effective therapy

  13. Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.

    Science.gov (United States)

    Saseen, J J; Porter, J A; Barnette, D J; Bauman, J L; Zajac, E J; Carter, B L

    1997-06-01

    The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.

  14. Statistical parametric mapping for effects of verapamil on olfactory connections of rat brain in vivo using manganese-enhanced MR imaging

    International Nuclear Information System (INIS)

    Soma, Tsutomu; Kurakawa, Masami; Koto, Daichi

    2011-01-01

    We investigated the effect of verapamil on the transport of manganese in the olfactory connections of rat brains in vivo using statistical parametric mapping and manganese-enhanced magnetic resonance (MR) imaging. We divided 12 7-week-old male Sprague-Dawley rats into 2 groups of six and injected 10 μL of saline into the right nasal cavities of the first group and 10 μL of verapamil (2.5 mg/mL) into the other group. Twenty minutes after the initial injection, we injected 10 μL of MnCl 2 (1 mol/L) into the right nasal cavities of both groups. We obtained serial T 1 -weighted MR images before administering the verapamil or saline and at 0.5, one, 24, 48, and 72 hours and 7 days after administering the MnCl 2 , spatially normalized the MR images on the rat brain atlas, and analyzed the data using voxel-based statistical comparison. Statistical parametric maps demonstrated the transport of manganese. Manganese ions created significant enhancement (t-score=36.6) 24 hours after MnCl 2 administration in the group administered saline but not at the same time point in the group receiving verapamil. The extent of significantly enhanced regions peaked at 72 hours in both groups and both sides of the brain. The peak of extent in the right side brain in the group injected with saline was 70.2 mm 3 and in the group with verapamil, 92.4 mm 3 . The extents in the left side were 64.0 mm 3 for the group with saline and 53.2 mm 3 for the group with verapamil. We applied statistical parametric mapping using manganese-enhanced MR imaging to demonstrate in vivo the transport of manganese in the olfactory connections of rat brains with and without verapamil and found that verapamil did affect this transport. (author)

  15. Suppressive effects of diltiazem and verapamil on delayed rectifier K(+)-channel currents in murine thymocytes.

    Science.gov (United States)

    Baba, Asuka; Tachi, Masahiro; Maruyama, Yoshio; Kazama, Itsuro

    2015-10-01

    Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and these channels play crucial roles in the lymphocyte activation and proliferation. Since diltiazem and verapamil, which are highly lipophilic Ca(2+) channel blockers (CCBs), exert relatively stronger immunomodulatory effects than the other types of CCBs, they would affect the Kv1.3-channel currents in lymphocytes. Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of these drugs on the channel currents and the membrane capacitance. Both diltiazem and verapamil significantly suppressed the peak and the pulse-end currents of the channels, although the effects of verapamil were more marked than those of diltiazem. Both drugs significantly lowered the membrane capacitance, indicating the interactions between the drugs and the plasma membranes. This study demonstrated for the first time that CCBs, such as diltiazem and verapamil, exert inhibitory effects on Kv1.3-channels expressed in lymphocytes. The effects of these drugs may be associated with the mechanisms of immunomodulation by which they decrease the production of inflammatory cytokines. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    International Nuclear Information System (INIS)

    Dakhel, Yaman; Jamali, Fakhreddin

    2006-01-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists

  17. Rapid solid-phase extraction method to quantify [{sup 11}C]-verapamil, and its [{sup 11}C]-metabolites, in human and macaque plasma

    Energy Technology Data Exchange (ETDEWEB)

    Unadkat, Jashvant D. [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States)], E-mail: jash@u.washington.edu; Chung, Francisco; Sasongko, Lucy; Whittington, Dale; Eyal, Sara [Department of Pharmaceutics, University of Washington, Box 357610, Seattle, WA 98195 (United States); Mankoff, David [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States); Collier, Ann C. [Department of Medicine, University of Washington, Box 359929, Seattle, WA 98195 (United States); Muzi, Mark; Link, Jeanne [Department of Radiology, University of Washington, Box 356004, Seattle, WA 98195 (United States)

    2008-11-15

    Introduction: P-glycoprotein (P-gp), an efflux transporter, is a significant barrier to drug entry into the brain and the fetus. The positron emission tomography (PET) ligand, [{sup 11}C]-verapamil, has been used to measure in vivo P-gp activity at various tissue-blood barriers of humans and animals. Since verapamil is extensively metabolized in vivo, it is important to quantify the extent of verapamil metabolism in order to interpret such P-gp activity. Therefore, we developed a rapid solid-phase extraction (SPE) method to separate, and then quantify, verapamil and its radiolabeled metabolites in plasma. Methods: Using high-performance liquid chromatography (HPLC), we established that the major identifiable circulating radioactive metabolite of [{sup 11}C]-verapamil in plasma of humans and the nonhuman primate, Macaca nemestrina, was [{sup 11}C]-D-617/717. Using sequential and differential pH elution on C{sub 8} SPE cartridges, we developed a rapid method to separate [{sup 11}C]-verapamil and [{sup 11}C]-D-617/717. Recovery was measured by spiking the samples with the corresponding nonradioactive compounds and assaying these compounds by HPLC. Results: Verapamil and D-617/717 recovery with the SPE method was >85%. When the method was applied to PET studies in humans and nonhuman primates, significant plasma concentration of D-617/717 and unknown polar metabolite(s) were observed. The SPE and the HPLC methods were not significantly different in the quantification of verapamil and D-617/717. Conclusions: The SPE method simultaneously processes multiple samples in less than 5 min. Given the short half-life of [{sup 11}C], this method provides a valuable tool to rapidly determine the concentration of [{sup 11}C]-verapamil and its [{sup 11}C]-metabolites in human and nonhuman primate plasma.

  18. Verapamil is Less Effective than Triamcinolone for Prevention of Keloid Scar Recurrence After Excision in a Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Rea, Suzanne M; Wood, Fiona M

    2016-01-01

    per subject and each wound half randomized to receive intralesional injections of triamcinolone (10 mg/ml) or verapamil (2.5 mg/ml) at monthly intervals (4 doses). Interim analysis was performed after 14 subjects were completed. Survival analysis demonstrated significantly higher keloid recurrence...... with verapamil compared to triamcinolone 12 months post-surgery (log-rank test, p = 0.01) and higher overall risk of recurrence with verapamil (hazard ratio 8.44, 95% CI 1.62-44.05). The study was terminated early according to the stopping guideline (p safe but not as effective...

  19. Uso do Verapamil em Gestantes Hipertensas Crônicas: análise do Fluxo das Artérias Uterinas e Umbilical Use of Verapamil in Chronic Hypertensive Pregnant Women: flow Analysis of Uterine Arteries and Umbilical Artery

    Directory of Open Access Journals (Sweden)

    Marcus Jose do Amaral Vasconcellos

    2000-06-01

    Full Text Available Objetivo: este trabalho, utilizando verapamil, um bloqueador dos canais lentos de cálcio, constituiu ensaio clínico randomizado, duplo-cego e placebo controlado, e objetivou procurar variação do fluxo uteroplacentário e fetoplacentário durante uso oral crônico do fármaco em gestantes com hipertensão crônica leve para moderada. Métodos: 123 pacientes divididas em dois grupos: grupo estudo (n = 61, submetidas a 240 mg/dia de verapamil, e grupo controle (n = 62, submetidas ao placebo. As pacientes randomizadas em grupos de quatro utilizaram a medicação ou placebo durante trinta dias. Um exame do fluxo das artérias uterinas e da artéria umbilical pela dopplervelocimetria foi registrado. Pelo cálculo da média e desvio padrão, foram comparados os valores dos índices de resistência (IR e pulsatilidade (IP e da relação sístole/diástole (A/B das artérias em estudo após administração dos comprimidos. Resultados: o grupo verapamil apresentou os seguintes valores médios para as artérias uterinas: IR = 0,82 (0,28, IP de 1,06 (0,12 e A/B de 2,42 (0,51. O grupo placebo mostrou: IR de 0,75 (0,35, IP de 1,00 (0,18 e A/B de 2,30 (0,38. Quando analisada a artéria umbilical, os valores foram para o grupo verapamil: IR = 0,73 (0,12, IP = 1,04 (0,13 e A/B = 2,94 (0,32. No grupo placebo, IR = 0,70 (0,14, IP = 1,03 (0,07 e A/B = 3,02 (0,78. A análise estatística das diferenças das médias por meio da razão F mostrou não haver diferença entre os dois grupos avaliados. Conclusão: este trabalho referenda o uso do verapamil entre gestantes com hipertensão crônica (leve para moderada, pois não oferece prejuízos no fluxo uteroplacentário e fetoplacentário.Purpose: this study, using verapamil, a slow calcium channel blocker, was a randomized, clinical, double blind and placebo controlled trial, whose objective was to observe if there was a uteroplacental and fetoplacental flow variation during its chronic oral use. Methods: 123

  20. Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil.

    Science.gov (United States)

    Eichelbaum, M; Somogyi, A; von Unruh, G E; Dengler, H J

    1981-01-01

    Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.

  1. Verapamil eliminates the hierarchical nature of activation frequencies from the pulmonary veins to the atria during paroxysmal atrial fibrillation.

    Science.gov (United States)

    Kushiyama, Yasunori; Osaka, Toshiyuki; Yokoyama, Eriko; Hasebe, Hideyuki; Kuroda, Yusuke; Kamiya, Kaichiro; Kodama, Itsuo

    2010-05-01

    There is evidence that verapamil promotes the persistence of paroxysmal atrial fibrillation (AF). Little is known about the underlying mechanisms. The purpose of this study was to determine the effect of verapamil on dominant frequencies (DFs) in the pulmonary veins (PVs) and atria during paroxysmal AF with reference to its potential arrhythmogenicity. Forty-three patients with paroxysmal AF were studied. Bipolar electrograms were recorded simultaneously during AF from the right atrial free wall (RAFW), coronary sinus (CS) and three PVs, or two PVs and the left atrial appendage (LAA). The DFs were obtained by fast Fourier transform analysis before and after infusion of verapamil (0.1 mg/kg, intravenously). At baseline, the maximum DF among the PVs (6.9 +/- 0.9 Hz) was significantly higher than the DF in the RAFW (6.2 +/- 0.7 Hz), CS (5.7 +/- 0.5 Hz), or LAA (5.9 +/- 0.7 Hz) (Patrial DF gradient (RAFW 0.7 +/- 0.9, CS 1.1 +/- 0.7, LAA 0.7 +/- 0.9 Hz). Verapamil increased the atrial DF to 6.9 +/- 0.8, 6.6 +/- 0.7, and 7.2 +/- 1.0 Hz in the RAFW, CS, and LAA, respectively (Patrial DF gradient was eliminated after verapamil (RAFW 0.2 +/- 0.8, CS 0.5 +/- 0.6, LAA -0.4 +/- 0.8 Hz; Patrial DF gradient during paroxysmal AF. Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. Dose calcium channel blocker verapamil decrease urinary VMA levels in sympathoadrenal hyperactive patients with posttraumatic stress disorder?

    Institute of Scientific and Technical Information of China (English)

    Munawar Alam Ansari; Shahida PAhmed; Zahida Memon

    2008-01-01

    Objective:The majority of the patients with posttraumatic stress disorders (PTSD)embrace augmented urina-ry flow of Vanillylmandelic Acid (VMA)than normal subjects owing to superior sympathetic doings,which steer to cardiovascular catastrophe.Urinary flow of VMA was evaluated as sympathoadrenal bustle marker in patients with posttraumatic stress disorder.Calcium ion shows a noteworthy dependability in nervousness owing to its special effects on brain synaptosomes.So this study was conducted to explore the effects of Verapamil on sympathoadrenal motion in patients with PTSD.Methods:Placebo controlled clinical tryout was conducted. At first hundred (100)PTSD patients were chosen and enrolled in the study,from department of Psychological Medicine Dow University of Health Sciences,Karachi.Verapamil 120 mg/day was specified in divided doses to group-I (n =50)patients and group-II (n =50)patients received placebo therapy on a daily basis for nine weeks.Each and every patient was monitored weekly,all the way through extent of study.Results:Under-neath the posttraumatic stress disorder,urinary excretion of VMA was greater.Calcium channel blocker vera-pamil additionally abolished the embellished retort in urinary flow of VMA appreciably in patients with PTSD. Conclusion:Verapamil was experiential to be exceedingly effectual treatment.It reduces VMA levels in u-rine,and on the whole cardiovascular threat in PTSD patients.

  3. Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids.

    Science.gov (United States)

    Ahuja, Rajeev B; Chatterjee, Pallab

    2014-06-01

    There is not much level 1 evidence based literature to guide management of hypertrophic scars and keloids despite an array of therapeutic modalities at disposal. Intralesional (i/l) triamcinolone injections have remained a gold standard in non surgical management. Sporadic reports on use of i/l verapamil suggest its efficacy. Since verapamil has not found sufficient mention as an effective alternative modality, it was decided to undertake a randomized study which could also address some additional clinical parameters. A randomized, parallel group and observer blinded comparison with 40 patients (48 scars) was carried out to compare the effects of i/l triamcinolone (T) (22 scars) and verapamil injections (V) (26 scars). 1.5 ml was the maximum indicative volume decided in the study protocol for both the drugs (triamcinolone @40 mg/ml and verapamil @ 2.5 mg/ml). Patients included were aged between 15-60 years with scars ranging between 0.5-5 cm (but total area roughly scars under 2 years duration. Patients with keloidal diathesis were excluded. Injections were scheduled every three weeks until complete flattening of the scar or eight sessions, which ever came earlier. No concomitant therapies like massage, silicone gel or pressure garments were used. Scar evaluation at each stage was done by serial photographic records as well as by Vancouver Scar Scale (VSS). Comparative survival analysis between the two drugs was done using Kaplan Meier curves, and VSS scores were analyzed using Wilcoxon test and log rank test. Mean zero VSS scores were achieved with treatments in respect of scar height (T-12 weeks, V-21 weeks), vascularity (T-15 weeks, V-18 weeks) and pliability (T-15 weeks, V-21 weeks). The improvement in scar vascularity and pliability kept pace with decrease in scar height, in both the groups. There was not much difference in the rate of change of scar pigmentation with either drug but almost 60% patients in both the groups regained normal pigmentation. Our

  4. Interaction of rivaroxaban with amiodarone, verapamil and diltiazem in patients with atrial fibrillation: terra incognita

    Directory of Open Access Journals (Sweden)

    S. N. Bel'diev

    2016-01-01

    Full Text Available Currently there are no generally accepted guidelines for the use of rivaroxaban together with amiodarone, verapamil or diltiazem in patients with creatinine clearance (CrCl<80 ml/min. Some researchers suggest that in renal failure amiodarone, verapamil and diltiazem contribute to a significant increase in plasma concentrations of rivaroxaban that is accompanied by increased risk of bleeding. According to preliminary calculations, it seems rational to reduce the dose of rivaroxaban when co-administered with these drugs: to 15 mg/day in patients with ClCr 50-79 ml/min and to 10 mg/day in patients with ClCr<50 ml/min.

  5. A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.

    Science.gov (United States)

    Wagner, Claudia C; Simpson, Marie; Zeitlinger, Markus; Bauer, Martin; Karch, Rudolf; Abrahim, Aiman; Feurstein, Thomas; Schütz, Matthias; Kletter, Kurt; Müller, Markus; Lappin, Graham; Langer, Oliver

    2011-02-01

    In microdose studies, the pharmacokinetic profile of a drug in blood after administration of a dose up to 100 μg is measured with sensitive analytical techniques, such as accelerator mass spectrometry (AMS). As most drugs exert their effect in tissue rather than blood, methodology is needed for extending pharmacokinetic analysis to different tissue compartments. In the present study, we combined, for the first time, AMS analysis with positron emission tomography (PET) in order to determine the pharmacokinetic profile of the model drug verapamil in plasma and brain of humans. In order to assess pharmacokinetic dose linearity of verapamil, data were acquired and compared after administration of an intravenous microdose and after an intravenous microdose administered concomitantly with an oral therapeutic dose. Six healthy male subjects received an intravenous microdose [0.05 mg] (period 1) and an intravenous microdose administered concomitantly with an oral therapeutic dose [80 mg] of verapamil (period 2) in a randomized, crossover, two-period study design. The intravenous dose was a mixture of (R/S)-[14C]verapamil and (R)-[11C]verapamil and the oral dose was unlabelled racaemic verapamil. Brain distribution of radioactivity was measured with PET whereas plasma pharmacokinetics of (R)- and (S)-verapamil were determined with AMS. PET data were analysed by pharmacokinetic modelling to estimate the rate constants for transfer (k) of radioactivity across the blood-brain barrier. Most pharmacokinetic parameters of (R)- and (S)-verapamil as well as parameters describing exchange of radioactivity between plasma and brain (influx rate constant [K(1)] = 0.030 ± 0.003 and 0.031 ± 0.005 mL/mL/min and efflux rate constant [k(2)] = 0.099 ± 0.006 and 0.095 ± 0.008 min-1 for period 1 and 2, respectively) were not statistically different between the two periods although there was a trend for nonlinear pharmacokinetics for the (R)-enantiomer. On the other hand, all

  6. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

    Directory of Open Access Journals (Sweden)

    Nooshin Masoudian

    2015-04-01

    Full Text Available Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on different stages of memory and learning processes including acquisition, consolidation and retrieval in mice. In this experimental study, 150 male albino mice with a mean weight of 30 g were used. The mice were trained in a passive avoidance-learning task (1 mA shock for 2 seconds for evaluation of memory acquisition and consolidation and 3 seconds for evaluation of memory retrieval. The effect of verapamil (1, 2.5, 5, 10, and 20 mg/kg on memory consolidation and the most effective dose of consolidation phase on memory acquisition and retrieval was assessed. For the evaluation of memory consolidation, the animals received the drug intraperitoneally immediately after training, while for evaluation of memory acquisition and retrieval, the drug was injected one hour before training. Memory retrieval test was performed 48 hours after training (the length of time it took the animal to enter the dark part of the device. The results showed that verapamil injection exerted no effect on memory acquisition and consolidation; nevertheless, it was capable to disrupt memory retrieval in 10 and 20 mg doses. These results indicate that as a phenylalkylamine calcium channel antagonist, high doses of verapamil can impair memory. Normal 0 false false false EN-US X-NONE AR-SA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso

  7. Verapamil and angiotensin-converting enzyme inhibitors in patients with coronary artery disease and reduced left ventricular ejection fraction

    DEFF Research Database (Denmark)

    Hansen, J F; Tingsted, L; Rasmussen, Verner

    1996-01-01

    Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been.......4 to 2.5 +/- 0.6 (p attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function...

  8. TREATMENT OPTIMIZATION IN PATIENTS WITH STABLE ANGINA PECTORIS: FOCUS ON VERAPAMIL SR

    Directory of Open Access Journals (Sweden)

    I. M. Sokolov

    2011-01-01

    Full Text Available Possibilities of angina pectoris pharmacotherapy are analyzed. Achievement of target heart rate (HR 55-60 beats per minute in these patients is possible due to three classes of antianginal medications that slow down HR: beta blockers (BB, If-channel inhibitors, nondihydropyridine calcium channel blockers (CCB. Nondihydropyridine CCB verapamil in slow release (SR formulation is focused. The main results of randomized clinical trials (APSIS, VHAS, CRIS, EVERESTH, VAMPHYRE, INVEST, VESPA, DAVIT-1, DAVIT-2, which have proven efficacy and safety, are presented. Verapamil SR is indicated for the treatment of angina pectoris in patients without history of myocardial infarction (MI; angina patients experienced MI without systolic heart failure and with contraindications to BB; angina with arterial hypertension; left ventricular diastolic dysfunction; peripheral arteries obliterating atherosclerosis; silent myocardial ischemia; vasospastic angina; angina associated with supraventricular cardiac arrhythmias (especially in permanent atrial fibrillation except Wolff-Parkinson-White and Lown-Ganong-Levine syndromes; after coronary angioplasty and the placement of bare metal stents.

  9. The effect of verapamil as an adjuvant agent with local anesthetic on sensory block level, hemodynamic and postoperative pain

    International Nuclear Information System (INIS)

    Tabaeizavareh, M.H.; Omranifard, M.

    2012-01-01

    Objective: Coadministration of verapamil with local anesthetics could potentiate the sensory block of peripheral nerve, increase the duration of sensory nerve block and reduce postoperative pain and analgesic consumption. The aim of this study was to investigate the effect of verapamil as an adjuvant with bupivacaine on level of sensory block, post-operative pain and analgesic consumption among patients undergone elective surgery in Isfahan. Methodology: In this prospective randomized interventional clinical double-blind study ASA physical status I or II male patients referred for elective lower abdominal surgery were enrolled. They randomized in group A (20 cc of 0.5% bupivacaine plus 5 mg verapamil) and B(20 cc of 0.5% bupivacaine plus 2 cc normal saline). The sensory level block, postoperative pain, opioid consumption and vomiting and nausa and hemodynamic state was recorded and compared in two groups. Results: Sixty two patients were studied. Mean of the sensory level block 20 minutes after stating epidural anesthesia and immediately after surgery, postoperative pain score, opioid consumption and nausea and vomiting and fluid intake was not significantly different in two groups (P>0.05). Mean of systolic and diastolic blood pressure and pulse rate changes was not significantly different in two groups (P>0.05). Conclusion: Verapamil as an adjuvant with bupivacaine could not significantly increase the level of sensory block and attenuate post-operative pain and analgesic consumption and hemodynamic condition of the patients. For more accurate results it is recommended to determine the effect of different dose of verapamil in larger sample size of the patients. Studying the effect of other Ca channel blockers would be favorable in this regard. (author)

  10. Mensuration of cardioangiopulmonary indices by radiocardiogram before and after the verapamil oral administration in subjects with chronic obstructive pulmonary disease. Mensuracao de indices cardiangiopulmonares, atraves do radiocardiograma antes e apos o emprego de verapamil por via oral em portadores de molestia pulmonar obstrutiva cronica

    Energy Technology Data Exchange (ETDEWEB)

    Lara, P F [Sao Paulo Univ., SP (Brazil). Inst. de Ciencias Biomedicas; Hueb, W A [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina

    1982-11-01

    Twenty subjects with chronic obstructive pulmonary disease were studied. The diagnosis was obtained from the history, clinical evaluation, pulmonary radiography, pulmonary and hepatic scintigraphies and spirometry. About 360 mg of verapamil was administered daily, every eight hours for ten days. Before and after drug administration, the arterial pressures, the spirometric measurements and nine cardiac roentgenographic indexes were measured. Vital capacity increased in all cases, but did not reach the normal levels. These data suggest that the effect of verapamil on the pulmonary circulation brought benefits to the subjects. This occurred either by direct pulmonary vasodilation, or by bronchodilation, reducing hypoxia. In all cases, the pulmonary resistance was diminished. Finally, verapamil seems to be a drug with real benefits in subjects with chronic obstructive pulmonary disease and we advise a continuation of the studies. (author).

  11. Efecto de la ciclosporina A y el verapamil en el pancreas endocrino de ratas

    Directory of Open Access Journals (Sweden)

    Nuris Ledón Naranjo

    1995-08-01

    Full Text Available Se demostró el efecto tóxico de la ciclosporina A (10 mg/kg sobre las células ß- pancreáticas, al ser suministrada diariamente durante una semana a ratas Wistar, así como la reducción de su toxicidad por tratamiento conjunto de verapamil (1 mg/kg. El tratamiento con ciclosporina A produjo hiperglicemia, disminuyó la tolerancia a la glucosa y los niveles de insulina, lo que ocasionó una reducción del incremento de peso en las ratas. Desde el punto de vista ultraestructural, se observó desorden y destrucción celular. Se concluyó que el tratamiento con ciclosporina A y verapamil simultáneamente evitó los efectos tóxicos de la ciclosporina A.

  12. Mensuration of cardioangiopulmonary indices by radiocardiogram before and after the verapamil oral administration in subjects with chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Lara, P.F.; Hueb, W.A.

    1982-01-01

    Twenty subjects with chronic obstructive pulmonary disease were studied. The diagnosis was obtained from the history, clinical evaluation, pulmonary radiography, pulmonary and hepatic scintigraphies and spirometry. About 360 mg of verapamil was administered daily, every eight hours for ten days. Before and after drug administration, the arterial pressures, the spirometric measurements and nine cardiac roentgenographic indexes were measured. Vital capacity increased in all cases, but did not reach the normal levels. These data suggest that the effect of verapamil on the pulmonary circulation brought benefits to the subjects. This occurred either by direct pulmonary vasodilation, or by bronchodilation, reducing hypoxia. In all cases, the pulmonary resistance was diminished. Finally, verapamil seems to be a drug with real benefits in subjects with chronic obstructive pulmonary disease and we advise a continuation of the studies. (author)

  13. Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins

    Directory of Open Access Journals (Sweden)

    Anna Rosati

    2004-01-01

    Full Text Available Most of the substances used as fluorescent probes to study drug transport and the effect of efflux blockers in multidrug resistant cells have many drawbacks, such as toxicity, unspecific background, accumulation in mitochondria. New fluorescent compounds, among which Bodipy‐FL‐verapamil (BV, have been therefore proposed as more useful tools. The uptake of BV has been evaluated by cytofluorimetry and fluorescence microscopy using cell lines that overexpress P‐glycoprotein (P388/ADR and LLC‐PK1/ADR or MRP (multidrug resistance‐related protein (PANC‐1 and clinical specimens from patients. The effect of specific inhibitors for P‐glycoprotein (verapamil and vinblastine or MRP (MK571 and probenecid has been also studied. BV intracellular concentrations were significantly lower in the two P‐glycoprotein overexpressing cell lines in comparison with the parental lines. In addition, verapamil and vinblastine increased the intracellular concentrations of the dye; MK571 and probenecid, two MRP inhibitors, increased BV levels in PANC‐1 cells, that express this protein. These findings were confirmed in clinical specimens from patients. Fluorescence microscopy revealed a faint fluorescence emission in P‐glycoprotein or MRP expressing cell lines; however, treatment with specific inhibitors significantly increased the fluorescence. BV is a useful tool for studying multidrug resistance proteins with different techniques such as cytofluorimetry and fluorescence microscopy, but does not discriminate between P‐glycoprotein and MRP. In comparison with other classic fluorescent probes, the assay with this dye is extremely rapid, simple, not toxic for cells, devoid of fluorescent background, and can be useful in the clinical settings.

  14. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1

    DEFF Research Database (Denmark)

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-01-01

    monolayers with a permeability of 5.7 × 10−5 cm sec−1 compared to an apical to basolateral permeability of 1.3 × 10−5 cm sec-1. The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 μmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6–1.6. The presence of telmisartan......Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake...... of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1...

  15. Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma.

    Science.gov (United States)

    Ganekal, Sunil; Dorairaj, Syril; Jhanji, Vishal; Kudlu, Krishnaprasad

    2014-01-01

    To evaluate the effect of 0.125% verapamil and 0.5% diltiazem eye drops on intraocular pressure (IOP) in steroid-induced glaucoma in rabbit eyes. A total of 18 rabbits with steroid-induced glaucoma were divided into three groups (A, B and C; n = 6 each). Right eyes in groups A, B and C received 0.5% diltiazem, 0.125% verapamil and 0.5% timolol eye drops twice daily for 12 days, respectively; whereas, left eyes received distilled water. IOP was measured with Tono-pen XL at baseline, day 4, day 8, and day 12 of treatment. Both 0.5% diltiazem and 0.125% verapamil eye drops significantly reduced IOP compared to control eyes (p cite this article: Ganekal S, Dorairaj S, Jhanji V, Kudlu K. Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma. J Current Glau Prac 2014;8(1):15-19.

  16. Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

    Science.gov (United States)

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares; Lepera, José Salvador

    2015-10-01

    Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Multidrug resistance circumvention by a new triazinoaminopiperidine derivative S9788 in vitro: definition of the optimal schedule and comparison with verapamil.

    Science.gov (United States)

    Julia, A. M.; Roché, H.; Berlion, M.; Lucas, C.; Milano, G.; Robert, J.; Bizzari, J. P.; Canal, P.

    1994-01-01

    The current work was undertaken to investigate the importance of exposure sequence and duration in achieving the maximum reversal action of S9788 on doxorubicin (DOX) cytotoxicity against cells that exhibit the (MDR) multidrug resistance phenotype: the MCF7/DOX cell line. Accumulation and release of DOX were examined in this cell line. The reversal effect was compared with that obtained with verapamil. S9788 activity was schedule dependent: when comparing incubation with S9788 before or after treatment with DOX, the best reversal factor was obtained in the case of a post-treatment incubation (65.6 +/- 7.7 vs 20.8 +/- 7.0). S9788 was a more potent modulating agent than verapamil, whatever the schedule of exposure of the cells to the reversal agent. The reversal of resistance after short-term DOX exposures was caused not only by prolonged cellular accumulation of DOX, but also by its prolonged retention after transfer of cells to DOX-free medium. A relationship was noted between cellular exposure to DOX and the cytotoxic effect, and so the reversal of resistance induced by S9788 appears to be directly linked to the level of cell exposure to DOX. This work provided a rationale for improving the schedule of administration of S9788 in clinical trials. PMID:8180016

  18. Effects of calcium antagonists on isolated bovine cerebral arteries: inhibition of constriction and calcium-45 uptake induced by potassium or serotonin

    International Nuclear Information System (INIS)

    Wendling, W.W.; Harakal, C.

    1987-01-01

    The purpose of this study was to determine the mechanisms by which organic calcium channel blockers inhibit cerebral vasoconstriction. Isolated bovine middle cerebral arteries were cut into rings to measure contractility or into strips to measure radioactive calcium ( 45 Ca) influx and efflux. Calcium channel blockers (10(-5) M verapamil or 3.3 X 10(-7) M nifedipine) and calcium-deficient solutions all produced near-maximal inhibition of both potassium- and serotonin-induced constriction. In calcium-deficient solutions containing potassium or serotonin, verapamil and nifedipine each blocked subsequent calcium-induced constriction in a competitive manner. Potassium and serotonin significantly increased 45 Ca uptake into cerebral artery strips during 5 minutes of 45 Ca loading; for potassium 45 Ca uptake increased from 62 to 188 nmol/g, and for serotonin from 65 to 102 nmol/g. Verapamil or nifedipine had no effect on basal 45 Ca uptake but significantly blocked the increase in 45 Ca uptake induced by potassium or serotonin. Potassium, and to a lesser extent serotonin, each induced a brief increase in the rate of 45 Ca efflux into calcium-deficient solutions. Verapamil or nifedipine had no effect on basal or potassium-stimulated 45 Ca efflux. The results demonstrate that verapamil and nifedipine block 45 Ca uptake through both potential-operated (potassium) and receptor-operated (serotonin) channels in bovine middle cerebral arteries

  19. Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and SQ109.

    Science.gov (United States)

    de Knegt, Gerjo J; van der Meijden, Aart; de Vogel, Corné P; Aarnoutse, Rob E; de Steenwinkel, Jurriaan E M

    2017-03-01

    Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for MDR-TB with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacin + linezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125 mg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256 mg/L and in 99% elimination after 6 days of exposure to 1 mg/L. Furthermore, colistin added to the moxifloxacin + linezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacin + linezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacin + linezolid treatment of MDR-TB. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity

    DEFF Research Database (Denmark)

    Biscardi, Monica; Teodori, Elisabetta; Caporale, Roberto

    2005-01-01

    36, CTS 27 and CTS 41, that are the most interesting compounds as MDR inhibitors, followed this course: MM 36>CTS 27>CTS 41, the last one presenting no cardiovascular activity. Chemosensivity to IDA in K-562/doxR cells and AML blasts could be enhanced in vitro by the adjuvant use of the six new VRP...... of these proteins, several attempts have been made to modulate their expression and activity (protein kinase C inhibitors, anti-MDR-1 oligonucleotides, pharmacological competitors and transcriptional inhibitors). Six new compounds (MM 36, CTS 4, CTS 9, CTS 12, CTS 27 and CTS 41), derived from verapamil (VRP), were......), in the presence or absence of inhibitors, showed that these compounds function well. All the resistance modifying agents potentiated IDA activity inducing a significant reduction (P

  1. A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by Verapamil Intoxication.

    Science.gov (United States)

    Yakut, Kahraman; Erdoğan, İlkay; Varan, Birgül; Atar, İlyas

    2017-12-01

    Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest. A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient's family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up. Brugada syndrome should be considered for patients who are admitted to the emergency ward

  2. Quantitative Comparison of Effects of Dofetilide, Sotalol, Quinidine, and Verapamil between Human Ex vivo Trabeculae and In silico Ventricular Models Incorporating Inter-Individual Action Potential Variability

    Directory of Open Access Journals (Sweden)

    Oliver J. Britton

    2017-08-01

    Full Text Available Background:In silico modeling could soon become a mainstream method of pro-arrhythmic risk assessment in drug development. However, a lack of human-specific data and appropriate modeling techniques has previously prevented quantitative comparison of drug effects between in silico models and recordings from human cardiac preparations. Here, we directly compare changes in repolarization biomarkers caused by dofetilide, dl-sotalol, quinidine, and verapamil, between in silico populations of human ventricular cell models and ex vivo human ventricular trabeculae.Methods and Results:Ex vivo recordings from human ventricular trabeculae in control conditions were used to develop populations of in silico human ventricular cell models that integrated intra- and inter-individual variability in action potential (AP biomarker values. Models were based on the O'Hara-Rudy ventricular cardiomyocyte model, but integrated experimental AP variability through variation in underlying ionic conductances. Changes to AP duration, triangulation and early after-depolarization occurrence from application of the four drugs at multiple concentrations and pacing frequencies were compared between simulations and experiments. To assess the impact of variability in IC50 measurements, and the effects of including state-dependent drug binding dynamics, each drug simulation was repeated with two different IC50 datasets, and with both the original O'Hara-Rudy hERG model and a recently published state-dependent model of hERG and hERG block. For the selective hERG blockers dofetilide and sotalol, simulation predictions of AP prolongation and repolarization abnormality occurrence showed overall good agreement with experiments. However, for multichannel blockers quinidine and verapamil, simulations were not in agreement with experiments across all IC50 datasets and IKr block models tested. Quinidine simulations resulted in overprolonged APs and high incidence of repolarization

  3. Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.)

    Czech Academy of Sciences Publication Activity Database

    Steinbach, C.; Fedorova, G.; Prokeš, Miroslav; Grabicová, K.; Máchová, J.; Grabic, R.; Valentová, O.; Kocour Kroupová, H.

    461-462, 461-462 (2013), s. 198-206 ISSN 0048-9697 Institutional support: RVO:68081766 Keywords : Bioconcentration * Embryo-larval test * Half-life time * Heart rate * Verapamil Subject RIV: GL - Fishing Impact factor: 3.163, year: 2013

  4. Circumvention of camptothecin-induced resistance during the adaptive cellular stress response.

    Science.gov (United States)

    Tiligada, Ekaterini; Papamichael, Konstantinos; Vovou, Ioanna; Delitheos, Andreas

    2006-01-01

    Camptothecin-11 (CPT-11) induces the adaptive stress response in yeast, conferring resistance via not fully characterized mechanisms. This study aimed at exploring, pharmacologically, the mechanisms underlying the CPT-11-induced resistance in yeast. Post-logarithmic yeast cultures were submitted to heat shock following preconditioning with suramin and with CPT-11, either alone or in combination with suramin, cycloheximide, sodium molybdate, okadaic acid, or verapamil. The stress response was evaluated by determining cell viability after heat shock. Preconditioning with CPT-11 or suramin conferred thermotolerance to yeast cells. Co-administration of CPT-11 with suramin, cycloheximide or okadaic acid reversed the CPT-11-induced thermotolerant phenotype, while sodium molybdate and verapamil had no effect on CPT-11-induced resistance. The antagonistic effect of the thermotolerance-inducers and the possible contribution of topoisomerase II activity and post-translational modifications mediated by the phosphatases PP1/2A in CPT-11-induced resistance may have important implications on the acquisition of resistance to stress in eukaryotic cells.

  5. A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by Verapamil Intoxication

    Directory of Open Access Journals (Sweden)

    Kahraman Yakut

    2017-12-01

    Full Text Available Background: Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest. Case Report: A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient’s family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up. Conclusion: Brugada syndrome should be

  6. The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Bülent Albayrak

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan, Group II (n: 20, trando- lapril + verapamil, Group III (n: 20, trandolapril +telmisartan + verapamil, and Group IV (n: 20, telmisartan + verapamil. At the end of a three-month therapy, within and between group compa- risons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR, electrolytes, serum albumin, low-density lipoprotein (LDL- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in protei- nuria and mean arterial blood pressure (MABP were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P <0.001 in Group I, 37% (P <0.001 in Group II, 42% (P <0.001 in Group III, and 43% (P <0.001 in Group IV; the reduction rate in MABP was 10.6% (P <0.001 in Group I, 13.7% (P <0.001 in Group II, 17.5% (P <0.001 in Group III, and 15.4% (P <0.001 in Group IV]. Decrease in HbA1C (before and after treatment was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients

  7. Determination of doxazosin and verapamil in human serum by fast LC-MS/MS: Application to document non-compliance of patients

    Czech Academy of Sciences Publication Activity Database

    Chytil, L.; Štrauch, B.; Cvačka, Josef; Marešová, V.; Widimský jr., J.; Holaj, R.; Slanař, O.

    2010-01-01

    Roč. 878, č. 30 (2010), s. 3167-3173 ISSN 1570-0232 Institutional research plan: CEZ:AV0Z40550506 Keywords : doxazosin * verapamil * hypertension Subject RIV: CC - Organic Chemistry Impact factor: 2.971, year: 2010

  8. Hepatic Proteome Sensitivity in Rainbow Trout after Chronically Exposed to a Human Pharmaceutical Verapamil*

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Sulc, Miroslav; Hulak, Martin; Randak, Tomas

    2012-01-01

    Verapamil (VRP), a cardiovascular pharmaceutical widely distributed and persistent in the aquatic environment, has potential toxicity to fish and other aquatic organisms. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the protein patterns that are differentially expressed in liver of rainbow trout exposed to sublethal concentrations of VRP (0.5, 27.0, and 270 μg/liter) for 42 days. Two-dimensional electrophoresis coupled with MALDI-TOF/TOF mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that the expression of six hepatic acidic proteins were markedly altered in the treatment groups compared with the control group; three proteins especially were significantly down-regulated in fish exposed to VRP at environmental related concentration (0.5 μg/liter). These results suggested that the VRP induce mechanisms against oxidative stress (glucose-regulated protein 78 and 94 and protein disulfide-isomerase A3) and adaptive changes in ion transference regulation (calreticulin, hyperosmotic glycine-rich protein). Furthermore, for the first time, protein Canopy-1 was found to be significantly down-regulated in fish by chronic exposure to VRP at environmental related levels. Overall, our work supports that fish hepatic proteomics analysis serves as an in vivo model for monitoring the residual pharmaceuticals in aquatic environment and can provide valuable insight into the molecular events in VRP-induced toxicity in fish and other organisms. PMID:21997734

  9. Structured Self-Rated Response to Iontophoresis with Verapamil and Dexamethasone in Peyronie’s Disease

    Directory of Open Access Journals (Sweden)

    Abas Kokab

    2014-01-01

    Full Text Available Introduction. New therapies evolve for the treatment of Peyronie's disease (PD including the application of dexamethasone and verapamil using Electro Motive Drug Administration (EMDA. Patients and Methods. Patients with PD were routinely offered Potaba, Vitamin E, tamoxifen or colchicine for 6 to 18 months and for those with no improvement, 18 applications of dexamethasone and verapamil using EMDA occurred over a 6 week period. All 30 patients receiving EMDA therapy completed a questionnaire before and after treatment. The data was collected from December 2004 to November 2009 and analysed to evaluate the effectiveness of the treatment. Results. Median age of patients was 59 (range 39–71. Curvature was the most common presenting complaint (73.3% followed by pain (23.3%, erectile dysfunction (13.3%, and lump (13.3%. 24/30 (80% reported an improvement in symptoms after EMDA. 16 of the responders (66.7% had a stable plaque for at least 6 months. The patients who complained of shortening of the penis (P=0.003 or lowered sexual desire (P=0.024 expressed subsequently significant response to treatment. There was statistically significant (P=0.019 improvement of penile deviation reported by responding men. Conclusion. A significant proportion of patients who received EMDA reported decreased curvature following iontophoresis. No serious adverse reactions developed.

  10. Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

    Directory of Open Access Journals (Sweden)

    Emami J.

    2008-05-01

    Full Text Available Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration. Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP, hydroxypropylmethyl cellulose (HPMC and sodium carboxymethyl cellulose (NaCMC in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients. Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics. Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K0 zero order release = 4.11 mg/h, MDT = 5.66 h and adhesive properties and did not show any interaction between polymers and drug based on

  11. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  12. Part I. Naltrexone-derived conjugate addition ligands for opioid receptors. Part II. Chemical and enantioselective aspects of the metabolism of verapamil

    International Nuclear Information System (INIS)

    Olsen, L.D.

    1987-01-01

    Selective chemoaffinity ligands to aid in identification and purification of opioid receptor subtypes were prepared from 6α- and 6β-naltrexol, obtained stereoselectively from the μ-receptor antagonist naltrexone. The targets were the 6α- and 6β-methacrylate ethers and 6α- and 6β-methacrylate esters prepared from reaction of 6α- and 6β-naltrexol with methyl α-(bromomethyl)acrylate or methacryloyl chloride. Of three methacrylate derivatives, the 6α-ether was the most potent in an opioid receptor binding assay with [ 3 H]-naltrexone. In the presence of sodium ion, preincubation of the 6α-ether resulted in recovery of about 60% of original [ 3 H]-naltrexone binding suggesting some irreversible effects. The methacrylate esters precipitated withdrawal in morphine dependent monkeys. The enantiomers of verapamil, a calcium channel antagonist, have different pharmacological and pharmacokinetic properties. The oxidative metabolism of verapamil was studied in rat and human liver microsomes and in man after a single oral dose

  13. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

    OpenAIRE

    Nooshin Masoudian; Nahid Masoudian; Ali Rashidy Pour; Abbas Ali Vafaiee; Sasan Andalib; Golnaz Vaseghi

    2015-01-01

    Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on ...

  14. Part I. Naltrexone-derived conjugate addition ligands for opioid receptors. Part II. Chemical and enantioselective aspects of the metabolism of verapamil

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, L.D.

    1987-01-01

    Selective chemoaffinity ligands to aid in identification and purification of opioid receptor subtypes were prepared from 6..cap alpha..- and 6..beta..-naltrexol, obtained stereoselectively from the ..mu..-receptor antagonist naltrexone. The targets were the 6..cap alpha..- and 6..beta..-methacrylate ethers and 6..cap alpha..- and 6..beta..-methacrylate esters prepared from reaction of 6..cap alpha..- and 6..beta..-naltrexol with methyl ..cap alpha..-(bromomethyl)acrylate or methacryloyl chloride. Of three methacrylate derivatives, the 6..cap alpha..-ether was the most potent in an opioid receptor binding assay with (/sup 3/H)-naltrexone. In the presence of sodium ion, preincubation of the 6..cap alpha..-ether resulted in recovery of about 60% of original (/sup 3/H)-naltrexone binding suggesting some irreversible effects. The methacrylate esters precipitated withdrawal in morphine dependent monkeys. The enantiomers of verapamil, a calcium channel antagonist, have different pharmacological and pharmacokinetic properties. The oxidative metabolism of verapamil was studied in rat and human liver microsomes and in man after a single oral dose.

  15. [Quality of conventional release verapamil prescription in patients with arterial hypertension].

    Science.gov (United States)

    Machado-Alba, J E; Giraldo-Giraldo, C; Machado-Duque, M E

    2015-01-01

    To identify patients who were being treated for hypertension with conventional release verapamil (CRV), and to notify the professional responsible for their health care on cardiovascular risk to which they are exposed and achieve a reduction in the number of patients who are treated with this drug. A quasi-experimental prospective before and after study without a control group was conducted on 7289 patients diagnosed with hypertension who were on treatment with CRV, between October 1, 2012 and December 31, 2012 in 8 Colombian cities, collected from a database for dispensing medicines. Socio-demographic and pharmacological variables were evaluated. A total of 108 educational interventions were performed on those responsible for their health care, and evaluated within three months with the proportion of suspension of the prescriptions of CRV being evaluated. Multivariate analysis was performed using SPSS 22.0. The mean age of patients was 67.9±11.8 years (range: 26-96 years), of which 70.6% were men. Withdrawal of treatment with CRV was achieved in a total of 1922 patients (26.3% of users), distributed as follows: 1160 (60.4%) were the presentation of 120mg, while 762 (39.6%) the 80mg. The variable being treated in the city of Medellin (OR: 17.6; 95% CI: 11.949 to 25.924; P<.01) was statistically significantly associated with the replacement of CRV for another antihypertensive. A relatively moderate adherence to recommendations about the proper use of CRV in hypertensive patients, was found. Intervention programs that reduce inappropriate prescribing of potential risks to patients of insurance companies and cities where the change was not achieved, must be enforced. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

  16. Experimentally-induced dissociation impairs visual memory.

    Science.gov (United States)

    Brewin, Chris R; Mersaditabari, Niloufar

    2013-12-01

    Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Site of action of calcium channel blockers in inhibiting endogenous pyrogen fever in rats.

    Science.gov (United States)

    Stitt, J T; Shimada, S G

    1991-09-01

    We have demonstrated that the Ca2+ channel blocker verapamil, administered intravenously, exerts an antipyretic effect on the febrile responses of rats to intravenously injected endogenous pyrogen (EP). We have also shown that the same intravenous dose of verapamil is ineffective in blocking fevers induced by the microinjection of exogenous prostaglandin E (PGE) into the organum vasculosum laminae terminalis (OVLT) of rats. Experiments were conducted to determine whether the site of this verapamil antipyresis was in the OVLT itself. The febrile responses of six male Sprague-Dawley rats to EP were determined at thermoneutrality. Verapamil (10 micrograms/rat) was microinjected directly into the OVLT, and the febrile responses to the EP dose were redetermined 15-30 min later. In every case the EP fevers were attenuated after verapamil pretreatment. Intra-OVLT injections of verapamil alone were without effect on body temperature. When the same dose of verapamil was injected into the OVLT 15 min before the injection of PGE into the same site, it had no effect on the ensuing PGE-induced fever. In view of the fact that less than 1/250th of the effective systemic dose of verapamil, when injected into the OVLT, was equally effective in blocking the EP fevers, we conclude that verapamil acts within the OVLT to block fever rather than peripherally. Furthermore, because verapamil administered into the OVLT does not block PGE fevers, it is unlikely that PGE produces fever by acting as a Ca2+ ionophore on hypothalamic neurons.

  18. Adherence to drug label recommendations for avoiding drug interactions causing statin-induced myopathy--a nationwide register study.

    Directory of Open Access Journals (Sweden)

    Jennifer Settergren

    Full Text Available To investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased.Cross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed.OR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60-1.25 and 0.92; 95% CI 0.69-1.23. Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56-0.68 and low dose 0.63; CI 0.58-0.68. Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55-0.76 and low dose 0.70; CI 0.63-0.78. Mean DDD (SD for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149 compared to patients on statin monotherapy 127 (93, (p<0.001.Prescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We found no evidence for avoiding co

  19. Anti-ischemic intervention as prognosis improvement in patients with coronary artery disease, with special focus on verapamil

    DEFF Research Database (Denmark)

    Jespersen, C M

    1996-01-01

    dysfunction, and thereby heart failure. In postinfarction patients intervention with verapamil significantly reduced the use of diuretics compared with placebo, indicating that anti-ischemic intervention may prevent heart failure. Ventricular arrhythmias are significantly associated with arrhythmic as well...... as non-arrhythmic death. The lack of preferential association of ventricular arrhythmias with arrhythmic death rather than nonarrhythmic death may imply that arrhythmias are provoked by ischemia. Antiarrhythmic intervention in postinfarction patients significantly increases death and arrhythmic events...... compared with placebo, especially in patients with residual ischemia. This may be due to a significant slowing of conduction during ischemia in patients treated with antiarrhythmic agents. In animal studies anti-ischemic agents prevent or suppress ventricular arrhythmias during ischemia, whereas...

  20. Comparison of Effects of Separate and Combined Sugammadex and Lipid Emulsion Administration on Hemodynamic Parameters and Survival in a Rat Model of Verapamil Toxicity.

    Science.gov (United States)

    Tulgar, Serkan; Kose, Halil Cihan; Demir Piroglu, Isılay; Karakilic, Evvah; Ates, Nagihan Gozde; Demir, Ahmet; Gergerli, Ruken; Guven, Selin; Piroglu, Mustafa Devrim

    2016-03-25

    Toxicity of calcium channel blockers leads to high patient mortality and there is no effective antidote. The benefit of using 20% lipid emulsion and sugammadex has been reported. The present study measured the effect of sugammadex and 20% lipid emulsion on hemodynamics and survival in a rat model of verapamil toxicity. In this single-blinded randomized control study, rats were separated into 4 groups of 7 rats each: Sugammadex (S), Sugammadex plus 20% lipid emulsion (SL), 20% lipid emulsion (L), and control (C). Heart rates and mean arterial pressures were monitored and noted each minute until death. Average time to death was 21.0±9.57 minutes for group C, 35.57±10.61 minutes for group S, 37.14±16.6 minutes for group L and 49.86±27.56 minutes for group SL. Time to death was significantly longer in other groups than in the control group (psugammadex and lipid emulsion had a positive effect on survival in patients with calcium channel blocker toxicity. Sugammadex and intralipid increased survival in a rat model of verapamil toxicity. The combination of both drugs may decrease cardiotoxicity. Sugammadex alone or combined with 20% lipid emulsion reduce the need for inotropic agents. The mechanism requires clarification with larger studies.

  1. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

  2. Status of experimental data for neutron induced reactions

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Mamoru [Tohoku Univ., Sendai (Japan)

    1998-11-01

    A short review is presented on the status of experimental data for neutron induced reactions above 20 MeV based on the EXFOR data base and journals. Experimental data which were obtained in a systematic manner and/or by plural authors are surveyed and tabulated for the nuclear data evaluation and the benchmark test of the evaluated data. (author). 61 refs.

  3. Evaluation of intralesional injection of hyaluronic acid compared with verapamil in Peyronie's disease: preliminary results from a prospective, double-blinded, randomized study.

    Science.gov (United States)

    Favilla, V; Russo, G I; Zucchi, A; Siracusa, G; Privitera, S; Cimino, S; Madonia, M; Cai, T; Cavallini, G; Liguori, G; D'Achille, G; Silvani, M; Franco, G; Verze, P; Palmieri, A; Torrisi, B; Mirone, V; Morgia, G

    2017-07-01

    Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid (HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil (ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease (PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function (IIEF-5) score. The difference between post- and pre-treatment plaque size was -1.36 mm (SD ± 1.27) for Group A and -1.80 mm (SD ± 2.47) for Group B (p-value = NS). IIEF-5 increased of 1.46 points (SD ± 2.18) in Group A and 1.78 (SD ± 2.48) in Group B (p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° (SD ± 5.63) from the baseline (p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement (PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I. © 2017 American Society of Andrology and

  4. Machine Induced Experimental Background Conditions in the LHC

    CERN Document Server

    Levinsen, Yngve Inntjore; Stapnes, Steinar

    2012-09-19

    The Large Hadron Collider set a new energy record for particle accelerators in late 2009, breaking the previous record held by Tevatron of 2 TeV collision energy. The LHC today operates at a collision energy of 7 TeV. With higher beam energy and intensity, measures have to be taken to ensure optimal experimental conditions and safety of the machine and detectors. Machine induced experimental background can severely reduce the quality of experimental triggers and track reconstruction. In a worst case, the radiation levels can be damaging for some of the subdetectors. The LHC is a particular challenge in this regard due to the vastly different operating conditions of the different experiments. The nominal luminosity varies by four orders of magnitude. The unprecedented stored beam energy and the amount of superconducting elements can make it challenging to protect the accelerator itself as well. In this work we have simulated and measured the machine induced background originating from various sources: the beam...

  5. Microcirculation alterations in experimentally induced gingivitis in dogs.

    Science.gov (United States)

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

  6. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

    2007-01-01

    In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...... in focal ischemia by pharmacological alteration of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle...... that the core body temperature was reduced by 1.7 degrees C for 24 hours after MCAO in rats treated with Talipexole. This treatment induced a significant reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that the reduction in infarct volume is related to drug-induced hypothermia...

  7. Prevention of shockwave induced functional and morphological alterations: an overview.

    Science.gov (United States)

    Sarica, Kemal; Yencilek, Faruk

    2008-03-01

    Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

  8. Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

    Science.gov (United States)

    ... An Experimental Contact Lens to Prevent Glaucoma-Induced Blindness By Sharon Reynolds Posted January 23, 2014 An ... group of conditions that can result in irreversible blindness. This vision loss can be reduced if glaucoma ...

  9. Numerical-experimental assessment of roughness-induced metal-polymer interface failure

    NARCIS (Netherlands)

    Beeck, van J.; Schreurs, P.J.G.; Geers, M.G.D.

    2015-01-01

    A numerical–experimental method is presented to study the initiation and growth of interface damage in polymer–steel interfaces subjected to deformation-induced steel surface roughening. The experimentally determined displacement field of an evolving steel surface is applied to a numerical model

  10. Intra- and interpersonal consequences of experimentally induced concealment

    NARCIS (Netherlands)

    Bouman, T.K.

    2003-01-01

    Secrecy, concealment, and thought supression are assumed to be important aspects of psychopathology. However, most studies address these from an intrapersonal perspective. This study investigates both the intra- as well as the interpersonal consequences of experimentally induced concealment. Two

  11. [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].

    Science.gov (United States)

    Fernández González, R; García Robles, R; Rodríguez Pérez, J C; Gómez Pajuelo, C; Moreno Carretero, E

    2001-01-01

    The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil

  12. Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

    Science.gov (United States)

    Ok, Seong-Ho; Byon, Hyo-Jin; Kwon, Seong-Chun; Park, Jungchul; Lee, Youngju; Hwang, Yeran; Baik, Jiseok; Choi, Mun-Jeoung; Sohn, Ju-Tae

    2015-01-01

    Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca2+]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca2+]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF. PMID:26664257

  13. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees......Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper...

  14. Mechanisms underlying odorant-induced and spontaneous calcium signals in olfactory receptor neurons of spiny lobsters, Panulirus argus.

    Science.gov (United States)

    Tadesse, Tizeta; Derby, Charles D; Schmidt, Manfred

    2014-01-01

    We determined if a newly developed antennule slice preparation allows studying chemosensory properties of spiny lobster olfactory receptor neurons under in situ conditions with Ca(2+) imaging. We show that chemical stimuli reach the dendrites of olfactory receptor neurons but not their somata, and that odorant-induced Ca(2+) signals in the somata are sufficiently stable over time to allow stimulation with a substantial number of odorants. Pharmacological manipulations served to elucidate the source of odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons. Both Ca(2+) signals are primarily mediated by an influx of extracellular Ca(2+) through voltage-activated Ca(2+) channels that can be blocked by CoCl2 and the L-type Ca(2+) channel blocker verapamil. Intracellular Ca(2+) stores contribute little to odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations. The odorant-induced Ca(2+) transients as well as the spontaneous Ca(2+) oscillations depend on action potentials mediated by Na(+) channels that are largely TTX-insensitive but blocked by the local anesthetics tetracaine and lidocaine. Collectively, these results corroborate the conclusion that odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons closely reflect action potential activity associated with odorant-induced phasic-tonic responses and spontaneous bursting, respectively. Therefore, both types of Ca(2+) signals represent experimentally accessible proxies of spiking.

  15. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine

    Directory of Open Access Journals (Sweden)

    Warhurst David C

    2003-09-01

    Full Text Available Abstract Background Chloroquine accumulates in the acidic digestive vacuole of the intraerythrocytic malaria parasite, and prevents the detoxication of haematin released during haemoglobin digestion. Changes in protein PfCRT in the digestive vacuole membrane of growing intra-erythrocytic stages of Plasmodium falciparum are crucial for resistance. Expressed in yeast, PfCRT resembles an anion channel. Depressed anion channel function could increase intralysosomal pH to reduce entry of basic drug, or enhanced function could reduce drug interaction with target haematin. The most important resistance-associated change is from positively-charged lysine-76 to neutral threonine which could facilitate drug efflux through a putative channel. It has been proposed that the resistance-reversing effect of verapamil is due to hydrophobic binding to the mutated PfCRT protein, and replacement of the lost positive charge, which repels the access of 4-aminoquinoline cations, thus partially restoring sensitivity. Desethylamodiaquine, the active metabolite of amodiaquine, which has significant activity in chloroquine-resistance, may also act similarly on its own. Methods Changes in physicochemical parameters in different CQ-resistant PfCRT sequences are analysed, and correlations with drug activity on lines transfected with different alleles of the pfcrt gene are examined. Results and conclusions The results support the idea that PfCRT is a channel which, in resistant parasites, can allow efflux of chloroquine from the digestive vacuole. Activity of the chloroquine/verapamil combination and of desethylamodiaquine both correlate with the mean hydrophobicity of PfCRT residues 72-76. This may partly explain clinical-resistance to amodiaquine found in the first chloroquine-resistant malaria cases from South America and enables tentative prediction of amodiaquine's clinical activity against novel haplotypes of PfCRT.

  16. Selective and Irreversible Induction of Necroptotic Cell Death in Lung Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib

    Directory of Open Access Journals (Sweden)

    Juan Sebastian Yakisich

    2017-01-01

    Full Text Available The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1 adherent cells growing under prolonged periods of serum starvation (PPSS and (2 cells growing as floating tumorspheres (FTs to evaluate the effect of Verapamil (VP in combination with Sorafenib (SF. Compared to cells growing under routine culture conditions (RCCs, PPPS cells or FTs were highly sensitive to short-term exposure (24 h to VP 100 μM + SF 5 μM (VP100 + SF5. Recovery experiments exposing cells to VP100 + SF5 for 24 h followed by incubation in drug-free media for 48 h demonstrated that while PPSS as well as FT cells were unable to recover, cancer cells and the noncancerous cell line Beas-2B growing under RCCs were less sensitive and were also able to recover significantly. VP100 + SF5 induced significant changes in the expression of protein associated with apoptosis, autophagy, and to a lesser extent necroptosis. Coincubation experiments with z-VAD-FMK, necrostatin 1, or chloroquine showed evidence that necroptosis played a central role. Our data demonstrates that highly resistant cancer cells can be selectively eliminated by VP + SF and that necroptosis plays a central role.

  17. Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    P. A. Virych

    2017-01-01

    Full Text Available Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM and gadolinium (300 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.

  18. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  19. Experimental identification of pedestrian-induced lateral forces on footbridges

    DEFF Research Database (Denmark)

    Ingólfsson, Einar Thór; Georgakis, Christos; Ricciardelli, Francesco

    2011-01-01

    combinations of frequencies (0.33-1.07 Hz) and amplitudes 4.5-48 mm). The experimental campaign involved seventy-one male and female human adults and covered approximately 55 km of walking distributed between 4954 individual tests. When walking on a laterally moving surface, motion-induced forces develop also......This paper presents a comprehensive experimental analysis of lateral forces generated by single pedestrians during continuous walking on a treadmill. Two different conditions are investigated; initially the treadmill is fixed and then it is laterally driven in a sinusoidal motion at varying...... and inter-subject variability. It is shown that the motion induced portion of the pedestrian load (on average) inputs energy into the structure in the frequency range (normalised by the average walking frequency) between approximately 0.6 and 1.2. Furthermore, it is shown that the load component in phase...

  20. Experimentally Induced Learned Helplessness: How Far Does it Generalize?

    Science.gov (United States)

    Tuffin, Keith; And Others

    1985-01-01

    Assessed whether experimentally induced learned helplessness on a cognitive training task generalized to a situationally dissimilar social interaction test task. No significant differences were observed between groups on the subsequent test task, showing that helplessness failed to generalize. (Author/ABB)

  1. Cholescintigraphy in experimentally induced obstructive and parenchymatous jaundice

    International Nuclear Information System (INIS)

    Baehre, M.; Biersack, H.J.; Hofmann, S.; Winkler, C.

    1979-01-01

    Animal studies have been performed in 30 dogs in order to obtain information concerning typical patterns of cholescintigraphy in acute obstructive jaundice. In 14 the choledochus was ligated and in 16 galactosamine-hepatitis was induced as an experimental model for parenchymatous jaundice. The results suggest a number of diagnostic criteria in obstructive disease. (Auth.)

  2. An experimental model of hemolysis-induced acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  3. Microbiological profile and calprotectin expression in naturally occurring and experimentally induced gingivitis.

    Science.gov (United States)

    Farina, Roberto; Guarnelli, Maria Elena; Figuero, Elena; Herrera, David; Sanz, Mariano; Trombelli, Leonardo

    2012-10-01

    This study was performed to evaluate the microbiological profile and the calprotectin expression in gingival crevicular fluid (GCF) in spontaneous and experimentally induced gingival inflammation. Thirty-seven periodontally healthy subjects were evaluated in real life conditions (N-O gingivitis) as well as after 21 days of experimental gingivitis trial (E-I gingivitis). During the experimental gingivitis trial, in one maxillary quadrant (test quadrant), gingival inflammation was induced by oral hygiene abstention, while in the contralateral (control) quadrant, oral hygiene was routinely continued. The results of the study showed that (1) the microbiological profile of quadrants where gingival inflammation was experimentally induced (i.e., E-I test quadrants) differed significantly from that of either quadrants where gingival inflammation was controlled by proper plaque control (i.e., E-I control quadrants) or quadrants with N-O gingivitis, and (2) GCF calprotectin was significantly higher at E-I test quadrants compared to either E-I control quadrants or quadrants with N-O gingivitis. A positive intrasubject correlation was found between GCF concentration of calprotectin at sites presenting N-O and E-I gingivitis. N-O and E-I gingivitis showed a different microbiological profile of the subgingival environment. GCF calprotectin is a reliable marker of gingival inflammation, and its concentration in N-O gingivitis is correlated with its expression in E-I gingivitis. The modality of plaque accumulation seems to affect the subgingival microbiological profile associated with a gingivitis condition. Calprotectin levels in GCF may be regarded as a promising marker of the individual susceptibility to develop gingival inflammation in response to experimentally induced plaque accumulation.

  4. Experimental study of ion-induced nucleation by radon decay

    International Nuclear Information System (INIS)

    He, F.; Hopke, P.K.

    1993-01-01

    In the environment, the presence of ions from natural radioactivity may increase the rate of new particle formation through ion-induced nucleation. A thermal diffusion cloud chamber (TDCC) has been built to experimentally study ion-induced nucleation where the ions are produced by gaseous radioactive sources. The critical supersaturation values and nucleation rates for methanol, ethanol, 1-propanol, and 1-butanol vapors on ions produced within the volume of the chamber by alpha decay of 222 Rn have been measured quantitatively at various radioactivity concentrations and supersaturations. The presence of ion tracks and the effect of an external electric field were also investigated. The alpha tracks and ion-induced nucleation formed by 222 Rn decay become visible at the critical supersaturation that is below the value needed for homogeneous nucleation. At this supersaturation, the nucleation rates increase substantially with increasing 222 Rn at low activity concentrations, but attain limiting values at higher concentrations. The experimental results indicate that the ionization by radon decay will promote ion-cluster formation and lower the free energy barriers. The formation of visible droplets is strongly dependent on the supersaturation. This study also confirms that the external electric field has a significant effect on the observed rates of nucleation

  5. Experimental and Theoretical Investigation of Shock-Induced Reactions in Energetic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Jeffrey J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Park, Samuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kohl, Ian Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knepper, Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Farrow, Darcie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tappan, Alexander S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    In this work, shock-induced reactions in high explosives and their chemical mechanisms were investigated using state-of-the-art experimental and theoretical techniques. Experimentally, ultrafast shock interrogation (USI, an ultrafast interferometry technique) and ultrafast absorption spectroscopy were used to interrogate shock compression and initiation of reaction on the picosecond timescale. The experiments yielded important new data that appear to indicate reaction of high explosives on the timescale of tens of picoseconds in response to shock compression, potentially setting new upper limits on the timescale of reaction. Theoretically, chemical mechanisms of shock-induced reactions were investigated using density functional theory. The calculations generated important insights regarding the ability of several hypothesized mechanisms to account for shock-induced reactions in explosive materials. The results of this work constitute significant advances in our understanding of the fundamental chemical reaction mechanisms that control explosive sensitivity and initiation of detonation.

  6. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch.

    Directory of Open Access Journals (Sweden)

    Alexandru D P Papoiu

    2011-03-01

    Full Text Available Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS.In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases. Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001.Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.

  7. Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats.

    Science.gov (United States)

    Aydemir, Orhan; Güler, Mete; Kaya, Mehmet Kaan; Deniz, Nurettin; Üstündağ, Bilal

    2012-12-01

    To determine whether ebselen has a protective effect or antioxidative potential in a sodium-selenite-induced experimental cataract model. Fırat University, Elazığ, Turkey. Experimental study. Twenty-one Sprague-Dawley rat pups were randomly divided into a control group, a sodium-selenite-induced-cataract group, and an ebselen-treated group; each group contained 7 rat pups. Rats in the control group received dimethyl sulfoxide (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO intraperitoneally 10 days postpartum. Rats in the ebselen group received 30 nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days. Cataract development was assessed weekly for 3 weeks by slitlamp examination and graded using a scale. Reduced glutathione (GSH), total nitrite, and malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3 weeks. In the control group, all lenses were clear. In the ebselen-treated group, the mean cataract stage was significantly lower than in the sodium-selenite-induced-cataract group (P = .022). The GSH levels were significantly lower in the sodium-selenite-induced-cataract group than in the control and ebselen groups (P ebselen group than in the sodium-selenite-induced-cataract group (P ebselen group (P = .001). Ebselen had a protective effect on cataract development in a sodium-selenite-induced experimental model. The protective effect of ebselen appears to be due to inhibition of oxidative stress. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  8. Loperamide Restricts Intracellular Growth of Mycobacterium tuberculosis in Lung Macrophages.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Sánchez, Guadalupe; González, Mitzi; Chávez, Jaime; Sarabia, Carmen; Torres, Martha; Sada, Eduardo

    2016-12-01

    New approaches for improving tuberculosis (TB) control using adjunct host-directed cellular and repurposed drug therapies are needed. Autophagy plays a crucial role in the response to TB, and a variety of autophagy-inducing drugs that are currently available for various medical conditions may serve as an adjunct treatment in pulmonary TB. Here, we evaluated the potential of loperamide, carbamazepine, valproic acid, verapamil, and rapamycin to enhance the antimicrobial immune response to Mycobacterium tuberculosis (Mtb). Human monocyte-derived macrophages (MDMs) and murine alveolar cells (MACs) were infected with Mtb and treated with loperamide, carbamazepine, valproic acid, verapamil, and rapamycin in vitro. Balb/c mice were intraperitoneally administered loperamide, valproic acid, and verapamil, and MACs were infected in vitro with Mtb. The induction of autophagy, the containment of Mtb within autophagosomes and the intracellular Mtb burden were determined. Autophagy was induced by all of the drugs in human and mouse macrophages, and loperamide significantly increased the colocalization of microtubule-associated protein 1 light chain 3 with Mtb in MDMs. Carbamazepine, loperamide, and valproic acid induced microtubule-associated protein 1 light chain 3 and autophagy related 16- like protein 1 gene expression in MDMs and in MACs. Loperamide also induced a reduction in TNF-α production. Loperamide and verapamil induced autophagy, which was associated with a significant reduction in the intracellular growth of Mtb in MACs and alveolar macrophages. The intraperitoneal administration of loperamide and valproic acid induced autophagy in freshly isolated MACs. The antimycobacterial activity in MACs was higher after loperamide treatment and was associated with the degradation of p62. In conclusion, loperamide shows potential as an adjunctive therapy for the treatment of TB.

  9. Alteration in DNA structure, molecular responses and Na+ -K+ -ATPase activities in the gill of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) in response to sub-lethal verapamil.

    Science.gov (United States)

    Ajima, Malachy N O; Pandey, Pramod K; Kumar, Kundan; Poojary, Nalini

    2018-01-01

    The ecotoxicological consequences of residues from pharmaceutical drugs on aquatic biota have necessitated the development of sensitive and reliable techniques to assess the impact of these xenobiotics on aquatic organisms. This study investigated the alteration in DNA structure, molecular responses and the activities of Na + -K + -ATPase and antioxidant enzymes in the gill of Nile tilapia, Oreochromis niloticus, exposed to long-term effects at the concentrations (0.14, 0.28 and 0.57mgL -1 ) of verapamil in static renewal system for 15, 30, 45 and 60 days. Evaluation of DNA structure, using single cell gel electrophoresis, revealed certain degree of DNA damages in the gill in a time and concentration-dependent relationship. Transcription of mRNA of superoxide dismutase (sod), catalase (cat) and heat shock protein (hsp70) genes in the gill of the fish showed the genes were up-regulated. Na + -K + -ATPase activity was inhibited in a concentration and time dependent manner. The indices of oxidative stress biomarkers (lipid peroxidation and carbonyl protein) as well as superoxide dismutase, glutathione peroxidase, glutathione-S-transferase were elevated in the treated fish in comparison to the control. Further, the level of reduced glutathione and catalase activity were inhibited at 0.28mgL -1 after day 30. Long-term exposure to sub-lethal concentration of verapamil can cause DNA damages, molecular effects and oxidative stress in O. niloticus. The biomarkers analysed can be used as early warning signals in environmental biomonitoring and assessment of drug contamination in aquatic ecosystem. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    Science.gov (United States)

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Xian-lin Wu

    2015-01-01

    Full Text Available Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP. The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS and multiple organ dysfunction syndromes (MODS to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

  12. Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

    Science.gov (United States)

    Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I

    2003-10-01

    An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

  13. Experimental and numerical analysis for magnetically induced vibrations of conducting structure

    International Nuclear Information System (INIS)

    Nishio, Satoshi; Nakahira, Masataka; Miura, H.; Isono, A.

    1993-01-01

    The coupling effect between the electromagnetic field and mechanical response of a conducting structure is of importance in magnetic fusion devices as tokamak machine. The electromagnetically induced motion of the structure due to the Lorentz force induces additional eddy currents and further modifies the dynamic characteristics of the system. This paper is concerned with numerical modeling of the dynamic field-structure interaction and its verification by experimental tests. Here, a finite element numerical model for mechanical deformation and a wiregrid numerical model for eddy currents are employed for non-ferrous and elastic conductors. A computer code has been developed for 3-D thin shell structure. Experimental tests for the code verification were carried out by using a rectangular thin copper plate. Three kinds of the plate supporting systems, i.e., a cantilever system, a fixed both ends system and a simply supported ends system were investigated. A good agreement between the numerical and experimental results was obtained. Therefore, the computer code developed here is available for analyzing the electromagnetomechanical behavior of the plasma facing components of the tokamak device. (author)

  14. Surfactant induced flows in thin liquid films : an experimental study

    NARCIS (Netherlands)

    Sinz, D.K.N.

    2012-01-01

    The topic of the experimental work summarized in my thesis is the flow in thin liquid films induced by non-uniformly distributed surfactants. The flow dynamics as a consequence of the deposition of a droplet of an insoluble surfactant onto a thin liquid film covering a solid substrate where

  15. Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma

    OpenAIRE

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

    2015-01-01

    Background Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. Methods The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg?1 of 5?% dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30?300 mgkg?1), acetazolamide (5 mg...

  16. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  17. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  18. Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

    Directory of Open Access Journals (Sweden)

    Veronica Ghiglieri

    2012-01-01

    Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

  19. Experimentally induced cam impingement in the sheep hip.

    Science.gov (United States)

    Siebenrock, Klaus A; Fiechter, Ruth; Tannast, Moritz; Mamisch, Tallal C; von Rechenberg, Brigitte

    2013-04-01

    Sheep hips have a natural non-spherical femoral head similar to a cam-type deformity in human beings. By performing an intertrochanteric varus osteotomy, cam-type femoro-acetabular impingement (FAI) during flexion can be created. We tested the hypotheses that macroscopic lesions of the articular cartilage and an increased Mankin score (MS) can be reproduced by an experimentally induced cam-type FAI in this ovine in vivo model. Furthermore, we hypothesized that the MS increases with longer ambulatory periods. Sixteen sheep underwent unilateral intertrochanteric varus osteotomy of the hip with the non-operated hip as a control. Four sheep were sacrificed after 14, 22, 30, and 38-weeks postoperatively. We evaluated macroscopic chondrolabral alterations, and recorded the MS, based on histochemical staining, for each ambulatory period. A significantly higher prevalence of macroscopic chondrolabral lesions was found in the impingement zone of the operated hips. The MS was significantly higher in the acetabular/femoral cartilage of the operated hips. Furthermore, these scores increased as the length of the ambulatory period increased. Cam-type FAI can be induced in an ovine in vivo model. Localized chondrolabral degeneration of the hip, similar to that seen in humans (Tannast et al., Clin Orthop Relat Res 2008; 466: 273-280; Beck et al., J Bone Joint Surg Br 2005; 87: 1012-1018), can be reproduced. This experimental sheep model can be used to study cam-type FAI. Copyright © 2012 Orthopaedic Research Society.

  20. Numerical and experimental investigation of the self-inducing turbine aeration capacity

    International Nuclear Information System (INIS)

    Achouri, Ryma; Dhaouadi, Hatem; Mhiri, Hatem; Bournot, Philippe

    2014-01-01

    Highlights: • Numerical and experimental study of k L a coefficient of a self-inducing turbine. • Validation of experimental results. • Numerical study of k L a variation with the variation of impeller submersion and blade inclination. • Numerical study of the flow field and hydrodynamic parameters. - Abstract: Self-inducing turbines are a model of mixers that ensure the aeration of a fluid field without using a sparger and a surface aerator. Nevertheless, this type of turbines remain quite complicated in terms of behavior of the fluid within the tank, and its actual aeration capacity varies depending on the type of turbine used. The studied turbine is self-inducing and made of three blades and each blade contains five holes. In this work, we evaluated experimentally – using the technique of dynamic oxygenation and deoxygenating – the aeration capacity of our impeller by calculating the volumetric mass transfer coefficient k L a for various submergences and various inclination angles of the blade. This work was then validated by a numerical modeling using the commercial code Fluent, and the flow within the tank as well as the evolution of the hydrodynamic parameters was also studied. The simulation is steady state with a VOF multiphase model and the realizable k–ε turbulence model. We finally concluded that k L a decreases with the increase of the inclination angle and with the increase of the submergence of our turbine. We could also study the hydrodynamic parameters of the flow such as the power number, the aeration number and the shear rate

  1. Diphtheria toxin-induced channels in Vero cells selective for monovalent cations

    International Nuclear Information System (INIS)

    Sandvig, K.; Olsnes, S.

    1988-01-01

    Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of 45 Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+, K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed

  2. Activity and milk compositional changes following experimentally induced Streptococcus uberis bovine mastitis.

    Science.gov (United States)

    Kester, H J; Sorter, D E; Hogan, J S

    2015-02-01

    Milk constituents and physical activity of cows experimentally infected with Streptococcus uberis mastitis were compared with those of uninfected cows. Twelve late-lactation Holsteins cows were paired based on milk production and parity. One cow in each pair was experimentally infected in the right front mammary gland with Strep. uberis. The remaining cow in each pair served as an uninfected control. Real-time analyses of milk constituents provided fat, protein, and lactose percentages at each milking. Pedometers were placed on the left front leg of all cows and activity was measured. Intramammary infections with Strep. uberis reduced milk yield in experimental cows by approximately 1.6kg/d in the first week after challenge compared with control cows. Lactose percentage in milk was reduced on d 3, 4, 5, and 6 after challenge in treatment cows compared with controls. Percentages of fat and protein in milk did not differ between infected and uninfected cows the week after infections were induced. Total steps per day were reduced and minutes resting per day were increased the week after experimental challenge in infected cows compared with control cows. The number of resting bouts did not differ between infected and uninfected cows. Changes in percentage of lactose in milk and animal activity caused by experimentally induced Strep. uberis mastitis were detected by the automated milk analyzer and pedometer systems. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  3. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  4. A novel PET imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier

    Science.gov (United States)

    Bankstahl, Jens P.; Bankstahl, Marion; Kuntner, Claudia; Stanek, Johann; Wanek, Thomas; Meier, Martin; Ding, Xiao-Qi; Müller, Markus; Langer, Oliver; Löscher, Wolfgang

    2013-01-01

    About one third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug-resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[11C]verapamil and different doses of co-administered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography (PET) can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 Tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[11C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k2, but not in distribution volume VT or influx rate constant K1, correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo. PMID:21677164

  5. Immediate effects of chocolate on experimentally induced mood states.

    Science.gov (United States)

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress.

  6. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Science.gov (United States)

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  7. Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

    OpenAIRE

    Abdelaleem, Shereen Abdelhakim; Hassan, Osama A.; Ahmed, Rasha F.; Zenhom, Nagwa M.; Rifaai, Rehab A.; El-Tahawy, Nashwa F.

    2017-01-01

    Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this ...

  8. Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

    Directory of Open Access Journals (Sweden)

    Olga Bloch

    2015-01-01

    Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

  9. Patterns of experimentally induced pain in pericranial muscles

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

    2006-01-01

    into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

  10. Transformation induced plasticity in maraging steel: an experimental study

    International Nuclear Information System (INIS)

    Nagayama, K.; Kitajima, Y.; Kigami, S.; Tanaka, K.

    2000-01-01

    The deformation behavior of a maraging TRIP (transformation induced plasticity) steel (MAVAL X12) is studied experimentally under a constant load. The existence of the back stress in the axial direction is directly proved by investigating the dilatation curves. Martensite-start lines are given under tensile, compressive and shear stresses. The evolution of TRIP strain and the maximum TRIP strain are determined. The alloy response during isothermal tensile test is explained in terms of influences both by the composite and transformation. (orig.)

  11. Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats

    International Nuclear Information System (INIS)

    Blatter, D.D.

    1987-01-01

    Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis. Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats. Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p 31 P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms. (orig.)

  12. Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality.

    Science.gov (United States)

    Botchkarev, Vladimir A; Sharov, Andrey A

    2016-03-01

    Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Paradoxical effects of rapamycin on experimental house dust mite-induced asthma.

    Directory of Open Access Journals (Sweden)

    Karin Fredriksson

    Full Text Available The mammalian target of rapamycin (mTOR modulates immune responses and cellular proliferation. The objective of this study was to assess whether inhibition of mTOR with rapamycin modifies disease severity in two experimental murine models of house dust mite (HDM-induced asthma. In an induction model, rapamycin was administered to BALB/c mice coincident with nasal HDM challenges for 3 weeks. In a treatment model, nasal HDM challenges were performed for 6 weeks and rapamycin treatment was administered during weeks 4 through 6. In the induction model, rapamycin significantly attenuated airway inflammation, airway hyperreactivity (AHR and goblet cell hyperplasia. In contrast, treatment of established HDM-induced asthma with rapamycin exacerbated AHR and airway inflammation, whereas goblet cell hyperplasia was not modified. Phosphorylation of the S6 ribosomal protein, which is downstream of mTORC1, was increased after 3 weeks, but not 6 weeks of HDM-challenge. Rapamycin reduced S6 phosphorylation in HDM-challenged mice in both the induction and treatment models. Thus, the paradoxical effects of rapamycin on asthma severity paralleled the activation of mTOR signaling. Lastly, mediastinal lymph node re-stimulation experiments showed that treatment of rapamycin-naive T cells with ex vivo rapamycin decreased antigen-specific Th2 cytokine production, whereas prior exposure to in vivo rapamycin rendered T cells refractory to the suppressive effects of ex vivo rapamycin. We conclude that rapamycin had paradoxical effects on the pathogenesis of experimental HDM-induced asthma. Thus, consistent with the context-dependent effects of rapamycin on inflammation, the timing of mTOR inhibition may be an important determinant of efficacy and toxicity in HDM-induced asthma.

  14. Experimental studies of the propagation of electrostatic ion perturbations by time-resolved laser-induced fluorescence

    International Nuclear Information System (INIS)

    Bachet, G.; Skiff, F.; Doveil, F.; Stern, R.A.

    2001-01-01

    Effects induced by the propagation of several kinds of electrostatic perturbation in a low-density collisionless argon plasma are observed with space, time, and velocity-resolved laser-induced fluorescence (LIF). The propagation of strong self-organized ion structures is observed and the associated electric field is determined. Snap shots of the ion phase space with a time resolution of 2 μs can be reconstructed from the experimental data. All the terms of the kinetic equation can also be determined from the data. A one-dimensional (1D) numerical simulation reproduces qualitatively the experimentally observed ion phase space behavior

  15. Functional magnetic resonances imaging of psychological functions with experimentally induced emotion

    International Nuclear Information System (INIS)

    Grodd, W.; Schneider, F.; Klose, U.; Naegele, T.

    1995-01-01

    In this study a T 2 * FLASH sequence (TR 240 ms, TE 60 ms, slice thickness 4 mm, α=40 , matrix 64x128) was used to investigate changes in signal intensity within the temporal lobe and the amygdala during experimentally induced emotions. Visual stimuli of happy [sad] facial portraits were presented to volunteers to induce changes in the subjects' mood while lying in the tomograph. In agreement with a previous PET study, a significant increase in signal intensity in the left amygdala was found during induction of a sad mood, while no comparable effect was visible during induction of a happy mood. (orig.) [de

  16. Oxidative stress in immature brain following experimentally-induced seizures

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava

    2013-01-01

    Roč. 62, Suppl.1 (2013), S39-S48 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : immature rats * experimentally-induced seizures * oxidative stress * mitochondrial dysfunction * antioxidant defense Subject RIV: FH - Neurology Impact factor: 1.487, year: 2013

  17. Immediate x-radiation induced contractions of the isolated guinea pig terminal ileum: the localization of the effect by drugs

    Energy Technology Data Exchange (ETDEWEB)

    Spruegel, W; Schubert, E; Mitznegg, P; Heim, F [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Pharmakologisches Inst.; Hasl, G; Pauly, H [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Radiologie

    1977-04-01

    Tone and motility of the isolated guinea pig ileum were increased by irradiation with a dose of 10 krad. The maximal effect corresponds to that induced by 0.001 ..mu..g/ml acetylcholine or 0.3 ..mu..g/ml nicotine. The pharmacological analysis of this effect performed with acetylcholine and nicotine and several blocking agents including hexamethonium, atropine, tetrodotoxin, diphenhydramine, and verapamil suggests that radiation acts on the postganglionic parasympathetic neuron and the neuromuscular synapse. The mechanism of radiation is likely to consist of both an increased release of acetylcholine from the postganglionic neuron and a sensibilization of the cholinergic receptor site at the smooth muscle cell. The latter effect is thought to result from an increased contractile action induced by acetylcholine or nicotine in the irradiated ileal smooth muscle.

  18. Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single-subject interventional study.

    Science.gov (United States)

    Eberhard, Jörg; Grote, Karsten; Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar; Schieffer, Bernhard; Stiesch, Meike

    2013-01-01

    We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, Pgingivitis. Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http://apps.who.int/trialsearch/Default.aspx.

  19. Comparative experimental study of cancer induced by ionizing radiations or by chemical carcinogens

    International Nuclear Information System (INIS)

    Lafuma, J.

    1983-01-01

    Animal experiments have contributed to specify a number of parameters used in setting human safety limits for ionizing radiation. In the same way, comparisons have been made between cancers induced in man and in animals in well-defined conditions. In order to use the same experimental data for chemical carcinogens, the mechanisms of carcinogenesis should be the same, i.e. additivity of responses instead of synergy of effects, which requires the development of a new experimental method [fr

  20. Foraminiferal survival after long term experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

  1. Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

    International Nuclear Information System (INIS)

    Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

    2017-01-01

    Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

  2. Effects of (-)-desmethoxyverapamil on heart and vascular smooth muscle

    International Nuclear Information System (INIS)

    Nawrath, H.; Raschack, M.

    1987-01-01

    (-)-Desmethoxyverapamil [also known as (-)-devapamil or (-)-D888] has been developed as a verapamil type radioligand for the study of calcium channels. In the present investigation, the effects of (-)-desmethoxyverapamil on action potential (AP) and force of contraction in heart muscle preparations and on tension and 45 Ca influx in vascular smooth muscle are described. In part, the effects were compared with the (+)-isomer of desmethoxyverapamil and the isomers of both verapamil and methoxyverapamil. In atrial and/or ventricular heart muscle preparations from guinea pigs, cats and man, (-)-desmethoxyverapamil decreased the force of contraction and shortened the AP duration. Slow response APs were depressed, whereas dV/dtmax of phase 0 of the AP remained unchanged. The rank order of potency of the (-)-isomers was as follows: desmethoxyverapamil greater than methoxyverapamil greater than verapamil. Potassium-induced contractures and 45 Ca influx were depressed by the (-)-isomers of desmethoxyverapamil, methoxyverapamil and verapamil in the same potency rank order as observed in heart muscle. The (+)-isomers exerted qualitatively similar effects at about 10 to 200 times higher concentrations. Correspondingly, the increase in potency of the racemic mixtures of the drugs was accompanied by increases in stereoselectivity. It is concluded that (-)-desmethoxyverapamil is the most potent stereoselective calcium antagonist of the verapamil type with respect to its effects on heart and vascular smooth muscle

  3. Effects of (-)-desmethoxyverapamil on heart and vascular smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Nawrath, H.; Raschack, M.

    1987-09-01

    (-)-Desmethoxyverapamil (also known as (-)-devapamil or (-)-D888) has been developed as a verapamil type radioligand for the study of calcium channels. In the present investigation, the effects of (-)-desmethoxyverapamil on action potential (AP) and force of contraction in heart muscle preparations and on tension and /sup 45/Ca influx in vascular smooth muscle are described. In part, the effects were compared with the (+)-isomer of desmethoxyverapamil and the isomers of both verapamil and methoxyverapamil. In atrial and/or ventricular heart muscle preparations from guinea pigs, cats and man, (-)-desmethoxyverapamil decreased the force of contraction and shortened the AP duration. Slow response APs were depressed, whereas dV/dtmax of phase 0 of the AP remained unchanged. The rank order of potency of the (-)-isomers was as follows: desmethoxyverapamil greater than methoxyverapamil greater than verapamil. Potassium-induced contractures and /sup 45/Ca influx were depressed by the (-)-isomers of desmethoxyverapamil, methoxyverapamil and verapamil in the same potency rank order as observed in heart muscle. The (+)-isomers exerted qualitatively similar effects at about 10 to 200 times higher concentrations. Correspondingly, the increase in potency of the racemic mixtures of the drugs was accompanied by increases in stereoselectivity. It is concluded that (-)-desmethoxyverapamil is the most potent stereoselective calcium antagonist of the verapamil type with respect to its effects on heart and vascular smooth muscle.

  4. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    Science.gov (United States)

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

  5. Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

    Directory of Open Access Journals (Sweden)

    Giono Silvia

    2002-06-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints. Methods P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis. Results M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints. Conclusion M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.

  6. Cartap-induced cytotoxicity in mouse C2C12 myoblast cell line and the roles of calcium ion and oxidative stress on the toxic effects.

    Science.gov (United States)

    Liao, Jiunn-Wang; Kang, Jaw-Jou; Jeng, Chian-Ren; Chang, Shao-Kuang; Kuo, Ming-Jang; Wang, Shun-Cheng; Liu, Michael R S; Pang, Victor Fei

    2006-02-15

    Our previous study has demonstrated that instead of neuromuscular blockage cartap, an organonitrogen insecticide, could cause a marked irreversible Ca2+-dependent contracture in both isolated mouse and rabbit phrenic nerve-diaphragms. We further examined the potential of direct myocytotoxicity of cartap and the possible roles of calcium ion and oxidative stress on cartap-induced muscle cell injury using the mouse myoblast cell line, C2C12. Cartap exerted a dose- and time-dependent cytotoxic effect in C2C12 cells measured by MTT colorimetric assay and trypan blue dye exclusion. The extracellular activities of both creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated in the cartap-treated groups at or greater than 100 microM. The isoenzymatic profiles showed that the elevations were mainly due to CK-3, LDH-3, and LDH-4. Following the addition of 0.5-2.5mM EGTA, a Ca2+ chelator, or 30-100 microM verapamil, an L-type Ca2+ channel blocker, the cartap-induced reduction in MTT metabolic rate of C2C12 cells was significantly restored in a dose-dependent manner in both EGTA and verapamil-treated cells. Furthermore, EGTA could significantly reduce the cartap-induced elevation in the levels of total extracellular CK and LDH activities. Additionally, cartap significantly increased the level of endogenous reactive oxygen species (ROS) in C2C12 cells in a dose- and time-dependent manner. The cartap-induced ROS generation could be significantly inhibited by antioxidants, including Vitamins C and E, catalase, and superoxide dismutase, with catalase the most effective. EGTA could significantly inhibit cartap-induced ROS generation in a dose-dependent manner. The results suggested that cartap could induce ROS generation in C2C12 cells via a Ca2+-dependent mechanism resulting in subsequent cytotoxicity, at least partially, to C2C12 cells. It is speculated that both Ca2+ and Ca2+-induced ROS may also play the central role on the myogenic contracture and myofiber injury

  7. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    Science.gov (United States)

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  8. Inflammation-induced preterm lung maturation: lessons from animal experimentation.

    Science.gov (United States)

    Moss, Timothy J M; Westover, Alana J

    2017-06-01

    Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

  9. Ionizing radiation-induced cancers. Experimental and clinical data

    International Nuclear Information System (INIS)

    Joveniaux, Alain.

    1978-03-01

    This work attempts to give an idea of radiocarcinogenesis, both experimental and clinical. Experimentally the possibility of radio-induced cancer formation has considerable doctrinal importance since it proves without question the carcinogenetic effect of radiations, and also yields basis information on the essential constants implicated in its occurrence: need for a latency time varying with the animal species and technique used, but quite long in relation to the specific lifetime of each species; importance of a massive irradiation, more conducive to cancerisation as long as it produces no necroses liable to stop the formation of any subsequent neoplasia; finally, rarity of is occurrence. Clinically although the cause and effect relationship between treatment and cancer is sometimes difficult to establish categorically, the fact is that hundreds of particularly disturbing observations remain and from their number often emerges under well-defined circumstances, an undeniable clinical certainty. Most importantly these observation fix the criteria necessary for the possibility of a radioinduced cancer to arise, i.e: the notion of a prior irradiation; the appearance of a cancer in the irradiation area; serious tissue damage in relation with an excessive radiation dose; a long latency period between irradition and appearance of the cancer [fr

  10. Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

    Science.gov (United States)

    González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

    2011-01-01

    Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

  11. Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

    Science.gov (United States)

    Louca, S; Ernberg, M; Christidis, N

    2013-06-01

    The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P granisetron on pain duration was significant only in women (P granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

  12. Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

    Directory of Open Access Journals (Sweden)

    Liming Liu

    2017-01-01

    Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

  13. Numerical and experimental evaluation of residual strains induced by pulsed laser welding

    International Nuclear Information System (INIS)

    Touvrey, C.; Bruyere, V.; Namy, P.

    2014-01-01

    The aim of the present study is to compare the residual strains induced by different welding processes during the assembly of two Ti6Al4V thin sheets. Several welding configurations and two means (pulsed laser and continuous one) are tested. The first part of the study intends to experimentally quantify strains induced by laser-matter interaction when one of the plates can freely bend. In this configuration the residual stresses are minimum, and consequently the strains measurement constitute a good indicator of the mechanical evolution. The displacements are in-situ reported thanks to a mechanical sensor. The second part of the study is dedicated to the numerical modeling of the processes. Unfortunately, the model is not completely predictive and appears to be oversimplified to describe the measured distortion. As it appears difficult to model the laser-matter interaction (especially in the case of many impacts recovering), we have adopted an equivalent approach to simulate the thermal evolution within the work pieces. An optimization procedure has been developed to determine an equivalent thermal flux, which leads to a melted zone shape in good agreement with experimental evaluations. The thermo-mechanical problem is computed by means of the finite elements software COMSOL Multiphysics. The results are compared to experimental data (displacement measurements) throughout the complete simulation. We plan to apply the complete model for more complex geometries, involving the generation of residual stresses. (authors)

  14. Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

    2014-01-01

    Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

  15. Status of experimental data of proton-induced reactions for intermediate-energy nuclear data evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yukinobu; Kawano, Toshihiko [Kyushu Univ., Fukuoka (Japan); Yamano, Naoki; Fukahori, Tokio

    1998-11-01

    The present status of experimental data of proton-induced reactions is reviewed, with particular attention to total reaction cross section, elastic and inelastic scattering cross section, double-differential particle production cross section, isotope production cross section, and activation cross section. (author)

  16. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    Banerjee, Chaitali; Goswami, Ramansu; Datta, Soma; Rajagopal, R.; Mazumder, Shibnath

    2011-01-01

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca 2+ ) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca 2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca 2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca 2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  17. Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.

    Directory of Open Access Journals (Sweden)

    June-Chul Lee

    Full Text Available Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.

  18. Experimental studies of keV energy neutron-induced reactions relevant to astrophysics and nuclear physics

    Energy Technology Data Exchange (ETDEWEB)

    Shima, T.; Kii, T.; Kikuchi, T.; Okazaki, F.; Kobayashi, T.; Baba, T.; Nagai, Y. [Tokyo Inst. of Tech. (Japan). Faculty of Science; Igashira, M.

    1997-03-01

    Nuclear reactions induced by keV energy neutrons provide a plenty of informations for studies of both astrophysics and nuclear physics. In this paper we will show our experimental studies of neutron- induced reactions of light nuclei in the keV energy region by means of a pulsed keV neutron beam and high-sensitivity detectors. Also we will discuss astrophysical and nuclear-physical consequences by using the obtained results. (author)

  19. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  20. Experimental investigation of flow induced dust acoustic shock waves in a complex plasma

    Energy Technology Data Exchange (ETDEWEB)

    Jaiswal, S., E-mail: surabhijaiswal73@gmail.com; Bandyopadhyay, P.; Sen, A. [Institute for Plasma Research, Bhat, Gandhinagar, Gujarat 382428 (India)

    2016-08-15

    We report on experimental observations of flow induced large amplitude dust-acoustic shock waves in a complex plasma. The experiments have been carried out in a Π shaped direct current glow discharge experimental device using kaolin particles as the dust component in a background of Argon plasma. A strong supersonic flow of the dust fluid is induced by adjusting the pumping speed and neutral gas flow into the device. An isolated copper wire mounted on the cathode acts as a potential barrier to the flow of dust particles. A sudden change in the gas flow rate is used to trigger the onset of high velocity dust acoustic shocks whose dynamics are captured by fast video pictures of the evolving structures. The physical characteristics of these shocks are delineated through a parametric scan of their dynamical properties over a range of flow speeds and potential hill heights. The observed evolution of the shock waves and their propagation characteristics are found to compare well with model numerical results based on a modified Korteweg-de-Vries-Burgers type equation.

  1. N-terminal-pro-B-type natriuretic peptide during pharmacological heart rate reduction in hyperthyroidism

    DEFF Research Database (Denmark)

    Schultz, M; Kistorp, C; Corell, P

    2009-01-01

    days. Before treatment, N-terminal-pro-B-type natriuretic peptide was independently associated with thyroid function (free triiodothyronine-index, r=0.64, p=0.001) and the hemoglobin concentration (r=-0.36, p=0.031). The verapamil treatment induced a decrease in parameters reflecting cardiac function......-index decreased from median 319 to 315 arbitrary units (p=0.039) and free triiodothyronine-index increased from 8.6 to 9.9 arbitrary units (p=0.010). No changes in echocardiographic parameters were observed. A decrease in resting heart rate in untreated hyperthyroidism due to verapamil treatment did not result...

  2. Oxidative defence reactions in sunflower roots induced by methyl-jasmonate and methyl-salicylate and their relation with calcium signalling.

    Science.gov (United States)

    Garrido, Inmaculada; Espinosa, Francisco; Alvarez-Tinaut, M Carmen

    2009-10-01

    Ca(2+) plays a critical role as second messenger in the signal-response coupling of plant defence responses, and methyl-jasmonate and methyl-salicylate are important components of signal transduction cascades activating plant defences. When intact axenic non-induced seedling roots of sunflower were treated with different Ca(2+) concentrations up to 1 mM, there was no significant increase in O(2)(*-) generation or DMAB-MBTH peroxidase (extracellular, ECPOX) activities in the apoplast, probably because these roots had enough Ca(2+) in their exo- and endocellular reservoirs. Both activities were strongly inhibited by the RBOH-NADPH oxidase inhibitor DPI and by the Ca(2+) surrogate antagonist La(3+), but the voltage-dependent Ca(2+) channel blocker verapamil was only inhibitory at concentrations higher than those active on animal L-type Ca(2+) channels. Concentrations >5 mM EGTA (chelating Ca(2+) in the apoplast) and Li(+) (inhibiting PI cycle dependent endogenous Ca(2+) fluxes) also inhibited both activities. W7, inhibitor of binding of Ca-CaM to its target protein, enhanced both activities, but the inactive analogue W5 showed a similar effect. Our data suggest that Ca(2+) from exocellular and, to a lesser extent, from endocellular stores is involved in oxidative activities, and that RBOH-NADPH oxidase is the main system supporting them. Ca(2+) activation of the PM cytosolic side of RBOH-NADPH oxidase is probably the key to Ca(2+) involvement in these processes. Roots induced by MeJA or MeSA showed significant enhancement of both oxidative activities, as corresponding to the oxidative burst evoked by the two phytohormones in the root apoplast. But while ECPOX activity showed a response to the effectors similar to that described above for non-induced roots, O(2)(*-) generation activity in the apoplast of induced roots was insensitive to EGTA, verapamil and Li(+), the inhibitors of exogenous and endogenous Ca(2+) fluxes; only DPI and La(3+) were inhibitory. As

  3. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    Science.gov (United States)

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  4. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET

    International Nuclear Information System (INIS)

    Kuntner, Claudia; Wanek, Thomas; Stundner, Gloria; Bankstahl, Jens P.; Bankstahl, Marion; Loescher, Wolfgang; Stanek, Johann; Mueller, Markus; Karch, Rudolf; Brauner, Rebecca; Meier, Martin; Ding, Xiaoqi; Langer, Oliver

    2010-01-01

    Overactivity of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is believed to play an important role in resistance to central nervous system drug treatment. (R)-[ 11 C]verapamil (VPM) PET can be used to measure the function of P-gp at the BBB, but low brain uptake of VPM hampers the mapping of regional differences in cerebral P-gp function and expression. The aim of this study was to evaluate the dose-response relationship of two potent P-gp inhibitors and to investigate if increased brain uptake of VPM mediated by P-gp inhibition can be used to assess regional differences in P-gp activity. Two groups of Sprague-Dawley rats (n = 12) underwent single VPM PET scans at 120 min after administration of different doses of the P-gp inhibitors tariquidar and elacridar. In an additional six rats, paired VPM PET scans were performed before and after administration of 3 mg/kg tariquidar. Inhibitor administration resulted in an up to 11-fold increase in VPM brain distribution volumes (DV) with half-maximum effective dose (ED 50 ) values of 3.0 ± 0.2 and 1.2 ± 0.1 mg/kg for tariquidar and elacridar, respectively. In paired PET scans, 3 mg/kg tariquidar resulted in regionally different enhancement of brain activity distribution, with lowest DV in cerebellum and highest DV in thalamus. Our data show that tariquidar and elacridar are able to increase VPM brain distribution in rat brain up to 11-fold over baseline at maximum effective doses, with elacridar being about three times more potent than tariquidar. Regional differences in tariquidar-induced modulation of VPM brain uptake point to regional differences in cerebral P-gp function and expression in rat brain. (orig.)

  5. Spectroscopic evaluation of painted layer structural changes induced by gamma radiation in experimental models

    International Nuclear Information System (INIS)

    Manea, Mihaela M.; Moise, Ioan V.; Virgolici, Marian; Negut, Constantin D.; Barbu, Olimpia-Hinamatsuri; Cutrubinis, Mihalis; Fugaru, Viorel; Stanculescu, Ioana R.; Ponta, Corneliu C.

    2012-01-01

    The degradation of cultural heritage objects by insects and microorganisms is an important issue for conservators, art specialists and humankind in general. Gamma irradiation is an efficient method of polychrome wooden artifacts disinfestation. Color changes and other modifications in the physical chemical properties of materials induced by gamma irradiation are feared by cultural heritage responsible committees and they have to be evaluated objectively and precisely. In this paper FTIR and FT-Raman spectroscopy methods were used to investigate the structural changes in some experimental models of tempera paint layers on wood following 11 kGy gamma irradiation at two dose rates. Radiation chemistry depends on the particular pigment, matrix formed by protein, resin (in case of varnished samples) and water presence. For the majority of painted layer in experimental models very small spectral variations were observed. Small changes in the FTIR spectra were observed for the raw sienna experimental model: for the higher dose rate the egg yolk protein oxidation peaks and the CH stretching bands due to lipids degradation products increased. - Highlights: ► Experimental models of tempera paint layers on wood were γ-irradiated at two dose rates. ► Changes induced by γ-irradiation were evaluated by vibrational spectroscopy. ► Minor spectral variations of painted layer were observed. ► Raw sienna FTIR spectra showed little changes of egg yolk and lipids at higher dose rate. ► Gamma irradiation is recommended for disinfection of painted wooden artifacts.

  6. Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study.

    Science.gov (United States)

    Abdelaleem, Shereen Abdelhakim; Hassan, Osama A; Ahmed, Rasha F; Zenhom, Nagwa M; Rifaai, Rehab A; El-Tahawy, Nashwa F

    2017-01-01

    Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this study. The rats were divided into 4 groups (control group, tramadol-treated group, and withdrawal groups). Tramadol was given to albino rats at a dose of 80 mg/kg body weight for 3 months and after withdrawal periods (7-15 days) rats were sacrificed. Long term use of tramadol induced severe histopathological changes in adrenal glands. Tramadol decreased the levels of serum cortisol and DHEAS hormones. In addition, it increased the level of adrenal MDA and decreased the genetic expression of glutathione peroxidase and thioredoxin reductase in adrenal gland tissues. All these changes started to return to normal after withdrawal of tramadol. Thus, it was confirmed that long term use of tramadol can induce severe adrenal insufficiency.

  7. Experimental studies on lung carcinogenesis and their relationship to future research on radiation-induced lung cancer in humans

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-03-01

    The usefulness of experimental systems for studying human lung carcinogenesis lies in the ease of studying components of a total problem. As an example, the main thrust of attack on possible synergistic interactions between radiation, cigarette smoke, and other irritants must be by means of research on animals. Because animals can be serially sacrificed, a systematic search can be made for progressive lung changes, thereby improving our understanding of carcinogenesis. The mechanisms of radiation-induced carcinogenesis have not yet been delineated, but modern concepts of molecular and cellular biology and of radiation dosimetry are being increasingly applied to both in vivo and in vitro exposure to determine the mechanisms of radiation-induced carcinogenesis, to elucidate human data, and to aid in extrapolating experimental animal data to human exposures. In addition, biologically based mathematical models of carcinogenesis are being developed to describe the nature of the events leading to malignancy; they are also an essential part of a rational approach to quantitative cancer risk assessment. This paper summarizes recent experimental and modeling data on radon-induced lung cancer and includes the confounding effects of cigarette-smoke exposures. The applicability of these data to understanding human exposures is emphasized, and areas of future research on human radiation-induced carcinogenesis are discussed. 7 refs., 2 figs., 3 tabs

  8. Experimental realization of an on-chip all-optical analogue to electromagnetically induced transparency.

    Science.gov (United States)

    Xu, Qianfan; Sandhu, Sunil; Povinelli, Michelle L; Shakya, Jagat; Fan, Shanhui; Lipson, Michal

    2006-03-31

    We provide the first experimental observation of structure tuning of the electromagnetically induced transparency-like spectrum in integrated on-chip optical resonator systems. The system consists of coupled silicon ring resonators with 10 microm diameter on silicon, where the coherent interference between the two coupled resonators is tuned. We measured a transparency-resonance mode with a quality factor of 11,800.

  9. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

    Science.gov (United States)

    Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

    2017-01-01

    This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

  10. Electron microscopic study of spontaneous and experimentally induced leukemia in IRC mice

    International Nuclear Information System (INIS)

    Hiraki, S.; Ranadive, K.J.; Dmochowski, L.

    1974-01-01

    Spontaneous, serially transplanted, and experimentally induced leukemias of ICRC mice were studied by electron microscopy in an attempt to detect the presence of virus particles, if any, and to observe the influence of chemical and hormonal treatment on the presence of these virus particles. The first series of experiments included spontaneous, serially transplanted, and radiation-induced leukemia. The paucity of type C virus particles was quite conspicuous in spontaneous leukemia. Serially transplanted and radiation-accelerated leukemic lesions showed the presence of some type C and intracisternal type A particles. Found in two of these leukemic lesions (thymus and lymphosarcoma), in addition to type C virus particles, were budding and some mature type B virus particles, and numerous intracytoplasmic type A particles. ''Viropexis'' of type B virus particles has been observed in the lymphosarcoma and in a leukemic thymus gland. The second series of experiments included leukemia induced in ovariectomized ICRC mice with 20-methylcholanthrene (MCA), pituitary transplants, and ovarian hormones (estradiol and estradiol-progesterone). In ovariectomized ICRC mice, leukemic lesions induced by MCA or pituitary transplants, or by MCA and pituitary transplants, showed type C virus particles and, in most cases, intracisternal type A particles. In leukemia induced in ovariectomized ICRC mice by MCA and estradiol, numerous intracytoplasmic type A particles were observed but no type C virus particles

  11. Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

    Science.gov (United States)

    Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

    1988-04-01

    To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

  12. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

    Directory of Open Access Journals (Sweden)

    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

  13. An experimental study on choroidal neovascularization induced by Krypton laser in rat model.

    Science.gov (United States)

    Cui, Jing; Liu, Yuanyuan; Zhang, Jingkai; Yan, Hua

    2014-01-01

    The purpose of this work was to study the efficacy and safety of choroidal neovascularization (CNV) formation induced by Krypton laser in Brown Norway (BN) rats, and observe the trend of the change of CNV after laser photocoagulation. Twenty-five male BN rats were involved in this study. Two eyes of one rat without any laser photocoagulation were randomly selected as the control group, and the other 48 eyes of 24 rats were selected as the experimental group. Eight eyes of four rats were randomly selected to receive the examinations of fundus fluorescein angiography (FFA), histopathology, and transmission electron microscopy 3, 7, 14, 21, 28, and 56 days after laser photocoagulation. After laser photocoagulation, the leakage appeared in burns on day 7 (59%), reached the peak on day 21 (84%), (p0.05). The thickness of CNV increased from day 7 to day 21 (p0.05). The experimental model of CNV can be successfully induced by Krypton laser in rats with a stable, long-lasting, and high success rate. After laser photocoagulation, the leakages appear on day 7, reach the peak on day 21, and remain stable after day 21.

  14. Transcriptional profiling of the bovine hepatic response to experimentally induced E. coli mastitis

    DEFF Research Database (Denmark)

    Jørgensen, Hanne Birgitte Hede; Buitenhuis, Bart; Røntved, Christine Maria

    2012-01-01

    The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally E. coli-induced ......The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally E. coli......-induced mastitis. At time = 0, each of 16 periparturient dairy cows received 20-40 CFU of live E. coli in one front quarter of the udder. A time series of liver biopsies was collected at -144, 12, 24 and 192 hours relative to time of inoculation. Changes in transcription levels in response to E. coli inoculation...... were analyzed using the Bovine Genome Array and tested significant for 408 transcripts over the time series (adjusted p0.05; abs(fold-change)>2). After 2-D clustering, transcripts represented three distinct transcription profiles: 1) regulation of gene transcription and apoptosis, 2) responses...

  15. [Effect of Capsicum annum L (pucunucho, ají mono) in gastric ulcer experimentally induced in rats].

    Science.gov (United States)

    Delgado Montero, Rocío; Flores Cortez, Daisy; Villalobos Pacheco, Eduardo

    2015-01-01

    To examine the effects of the Capsicum annum L lyophilized fruit extract in experimentally-induced gastric ulcer in rats. We used the model of indomethacin gastric ulcer-induced and the gastric ulcer model induced by pylorus ligation in rats. The rats were divided in five treatment groups as follow: G1: Distilled water 1 ml/Kg; G2: Ranitidine 50 mg/kg, G3: Capsicum 10mg/kg, G4: Capsicum 100 mg/kg, G5: Capsicum 1000 mg/kg. The results of the first model showed an ulcer inhibition of 60,4% and 66,7% using the doses of Capsicum at 10 mg/kg and 100 mg/kg, respectively. The results of the second model showed that neither the pH nor the volume of the gastric content were modified by the administered extract (p >0.05); however, by using the doses of Capsicum at 100 mg/kg and 1000 mg/kg, there was clearly an ulcer inhibition of 75.59% and 81.63% respectively, which were even greater than the inhibition obtained by ranitidine (75.51%). Therefore, in this experiment we demonstrated that the Capsicum annum L lyophilized fruit extract has a gastroprotective effect in experimentally-induced gastric ulcer in rats.

  16. Long-term treadmill exercise-induced neuroplasticity and associated memory recovery of streptozotocin-induced diabetic rats: an experimenter blind, randomized controlled study.

    Science.gov (United States)

    You, Joshua Sung H; Kim, Chung-Ju; Kim, Mee Young; Byun, Yong Gwon; Ha, So Young; Han, Bong Suk; Yoon, Bum Chul

    2009-01-01

    We investigated a long-term exercise-induced neuroplasticity and spatial memory recovery in 15 rats in a treadmill as follows: normal control rats (NC), streptozotocin (STZ)-induced diabetic control rats (DC), and STZ-induced diabetic rats exercising in a treadmill (DE). As per the DE group, the running exercise in a treadmill was administered for 30 minutes a day for 6 weeks. Neuronal immediate-early gene (IEG) expression (c-Fos) in the hippocampus and radial arm maze (RAM) tests were measured and revealed that the c-Fos levels in DE were significantly higher than those in NC and DC (p memory performance scores, obtained from the RAM test, were significantly different among the three groups (p memory scores of NC and DE were higher than those of DC (p memory. This is the first experimental evidence in literature that supports the efficacy of exercise-induced neuroplasticity and spatial motor memory in diabetes care.

  17. Experimental and theoretical studies on X-ray induced secondary electron yields in Ti and TiO2

    International Nuclear Information System (INIS)

    Iyasu, Takeshi; Tamura, Keiji; Shimizu, Ryuichi; Vlaicu, Mihai Aurel; Yoshikawa, Hideki

    2006-01-01

    Generation of X-ray induced secondary electrons in Ti and TiO 2 was studied from both experimental and theoretical approaches, using X-ray photoelectron spectroscopy (XPS) attached to a synchrotron radiation facility and Monte Carlo simulation, respectively. The experiment revealed that the yields of secondary electrons induced by X-rays (electrons/photon) at photon energies to 4950 and 5000eV for Ti and TiO 2 are δ Ti (4950eV)=0.002 and δ Ti (5000eV)=0.014 while those for TiO 2 are δ TiO 2 (4950eV)=0.003 and δ TiO 2 (5000eV)=0.018. A novel approach to obtain the escape depth of secondary electrons has been proposed and applied to Ti and TiO 2 . The approach agreed very well with the experimental data reported so far. The Monte Carlo simulation predicted; δ Ti * (4950eV)=0.002 and δ Ti * (5000eV)=0.011 while δ TiO 2 * (4950eV)=0.003 and δ TiO 2 * (5000eV)=0.015. An experimental examination on the contribution of X-ray induced secondary electrons to photocatalysis in TiO 2 has also been proposed

  18. Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

    Directory of Open Access Journals (Sweden)

    Shereen Abdelhakim Abdelaleem

    2017-01-01

    Full Text Available Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this study. The rats were divided into 4 groups (control group, tramadol-treated group, and withdrawal groups. Tramadol was given to albino rats at a dose of 80 mg/kg body weight for 3 months and after withdrawal periods (7–15 days rats were sacrificed. Long term use of tramadol induced severe histopathological changes in adrenal glands. Tramadol decreased the levels of serum cortisol and DHEAS hormones. In addition, it increased the level of adrenal MDA and decreased the genetic expression of glutathione peroxidase and thioredoxin reductase in adrenal gland tissues. All these changes started to return to normal after withdrawal of tramadol. Thus, it was confirmed that long term use of tramadol can induce severe adrenal insufficiency.

  19. Experimental and theoretical study of steam condensation induced water hammer phenomena

    International Nuclear Information System (INIS)

    Barna, Imre Ferenc; Baranyai, Gabor; Ezsoel, Gyoergy

    2009-01-01

    We investigate steam condensation induced water hammer (waha) phenomena and present experimental and theoretical results. Some of the experiments were performed in the PMK-2 facility, which is a full-pressure thermohydraulic model of the nuclear power plant of VVER-440/312 type and located in the Atomic Energy Research Institute Budapest, Hungary. Other experiments were done in the ROSA facility in Japan. On the theoretical side waha is studied and analyzed with the WAHA3 model based on two-phase flow six first-order partial differential equations that present one dimensional, surface averaged mass, momentum and energy balances. A second order accurate high-resolution shock-capturing numerical scheme was applied with different kind of limiters in the numerical calculations. The applied two-fluid model shows some similarities to Relap5 which is widely used in the nuclear industry to simulate nuclear power plant accidents. Experimentally measured and theoretically calculated waha pressure peaks are in qualitative agreement. (author)

  20. Effects of a Tumor Necrosis Factor-α Antagonist on Experimentally Induced Rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Kim

    2011-01-01

    Full Text Available This prospective, randomized, and controlled study examined the effects of tumor necrosis factor soluble receptor type I (sTNFRI, a TNF-α antagonist on experimentally induced rhinosinusitis in rats. The experimental groups received an instillation of lipopolysaccharide (LPS plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group, an instillation of sTNFRI (sTNFRI group, an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group, or no additional treatment (LPS group. Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR. The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression. This study shows that sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats.

  1. Hepatoprotective and Antioxidant activity of Scoparia dulcis Linn, against N Nitrosodiethylamine (DEN) induced Hepatotoxicity in experimental Rats

    OpenAIRE

    Langeswaran K; Jagadeesan A. J; Vijayaprakash S; Balasubramanian M. P

    2012-01-01

    Scoparia dulcis Linn, belongs to the family Scrophulariaceae and have speculated Medicinal properties. In this present investigation, the antioxidant and hepatoprotective activity of the aqueous extracts of Scoparia dulcis was evaluated against N-nitrosodiethylamine (DEN) induced liver cirrhosis in experimental rats. In group III hepatotoxicity induced animals, an oral dose of 500 mg/kg, of the aqueous extracts of Scoparia dulcis exhibited a significant (P

  2. Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model

    Directory of Open Access Journals (Sweden)

    S. Rochelle Lewis

    2014-01-01

    Full Text Available Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM, affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.

  3. Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.

    Science.gov (United States)

    Lewis, S Rochelle; Ellison, Siobhan P; Dascanio, John J; Lindsay, David S; Gogal, Robert M; Werre, Stephen R; Surendran, Naveen; Breen, Meghan E; Heid, Bettina M; Andrews, Frank M; Buechner-Maxwell, Virginia A; Witonsky, Sharon G

    2014-01-01

    Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5-1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.

  4. Elastase-induced pulmonary emphysema: insights from experimental models

    Directory of Open Access Journals (Sweden)

    Mariana A. Antunes

    2011-12-01

    Full Text Available Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.Diversos estímulos podem ser utilizados para reproduzir características histológicas e funcionais do enfisema humano, uma das principais causas de incapacidade e morte. Uma vez que a fumaça de cigarro é a principal causa de enfisema em humanos, estudos experimentais têm tentado reproduzir esta situação. No entanto, esse é um método dispendioso e complicado para a indução do enfisema e, alternativas mais simples e eficazes, têm sido pesquisadas. Entre essas abordagens, enzimas elastolíticas vêm sendo amplamente utilizadas para reproduzir algumas das características do enfisema humano, tais como: aumento dos espaços a

  5. Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate

    DEFF Research Database (Denmark)

    Lange, Sofie Cecilie; Winkler, Ulrike; Andresen, Lars

    2015-01-01

    is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis...... biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined...... in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis...

  6. Experimentally induced chocolate craving leads to an attentional bias in increased distraction but not in speeded detection.

    Science.gov (United States)

    Smeets, Elke; Roefs, Anne; Jansen, Anita

    2009-12-01

    In the present study, the causal influence of chocolate craving on attentional bias for chocolate-related information was examined by experimentally inducing chocolate craving in a sample of high trait chocolate cravers vs. low trait chocolate cravers. A sample of 35 high trait chocoholics and 33 low trait chocolate cravers were randomly assigned to either the exposure condition in which craving was manipulated or the non-exposure condition. To measure attentional bias, a pictorial version of the visual search paradigm [Smeets, E., Roefs, A., van Furth, E., & Jansen, A. (2008). Attentional bias for body and food in eating disorders: increased distraction, speeded detection, or both? Behaviour Research and Therapy, 46, 229-238] was used, assessing two components: distraction and detection. It was found that experimentally induced chocolate craving led to increased distraction by chocolate pictures in the high trait chocolate cravers, in comparison to the low trait chocolate cravers. Moreover, this measure of distraction correlated strongly with self-reported craving, but only in the chocoholics and in the exposure condition. In the non-exposure condition, high trait chocolate cravers showed speeded detection of chocolate pictures relative to non-chocoholics, but this component did not correlate with self-reported craving. It is concluded that experimentally induced craving for chocolate causes a bias in, specifically the increased distraction component of attention in high trait chocolate cravers.

  7. Integrated system for production of neutronics and photonics calculational constants. Neutron-induced interactions: index of experimental data

    International Nuclear Information System (INIS)

    MacGregor, M.H.; Cullen, D.E.; Howerton, R.J.; Perkins, S.T.

    1976-01-01

    Indexes to the neutron-induced interaction data in the Experimental Cross Section Information Library (ECSIL) as of July 4, 1976 are tabulated. The tabulation has two arrangements: isotope (ZA) order and reaction-number order

  8. Integrated system for production of neutronics and photonics calculational constants. Neutron-induced interactions: index of experimental data

    Energy Technology Data Exchange (ETDEWEB)

    MacGregor, M.H.; Cullen, D.E.; Howerton, R.J.; Perkins, S.T.

    1976-07-04

    Indexes to the neutron-induced interaction data in the Experimental Cross Section Information Library (ECSIL) as of July 4, 1976 are tabulated. The tabulation has two arrangements: isotope (ZA) order and reaction-number order.

  9. Role of hypoxia-inducible factor-α in hepatitis-B-virus X protein-mediated MDR1 activation

    International Nuclear Information System (INIS)

    Han, Hyo-Kyung; Han, Chang Yeob; Cheon, Eun-Pa; Lee, Jaewon; Kang, Keon Wook

    2007-01-01

    The transition from chemotherapy-responsive cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multi-drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx) increases the transcriptional activity and protein level of MDR1 in a hepatoma cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1α (HIF-1α) and induced the nuclear translocation of C/EBPβ. Reporter gene analyses showed that HBx increased the reporter activity in the cells transfected with the reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene activity was significantly inhibited by HIF-1α siRNA but not by overexpression of C/EBP dominant negative mutant. These results imply that HBx increases the MDR1 transporter activity through the transcriptional activation of the MDR1 gene with HIF-1α activation, and suggest HIF-1α for the therapeutic target of HBV-mediated chemoresistance

  10. Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

    Science.gov (United States)

    Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

    2017-11-01

    To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

  11. The Effect of Experimental Parkinson on Formalin-Induced Pain in Rat

    Directory of Open Access Journals (Sweden)

    Mohammad Sofiabadi

    2014-04-01

    Full Text Available Background & Objectives : Pain is one of the preceding claims of Parkinson's disease (PD, that its mechanisms have not been fully identified. The purpose of this study was to investigate the chemical pain responses induced by subcutaneous injection of formalin in male parkinsonized rats.   Method : In this experimental study, 40 Wistar male rats were used and PD was established by stereotaxic injection of 6-OHDA toxin into the striatum. Parkinson's disease severity determined by apomorphine-induced rotation test and then the pain response of 4 groups, the control, sham and 2 weak or full Parkinson groups, were evaluated using formalin test. Data were analyzed using ANOVA and Tukey test.   Results : In both acute and chronic phases of the formalin test, the symptoms of pain in different groups were same, but at the interphase stage, pain intensity increased more in Parkinson 's rats, especially in full PD group compared to control (p<0.01.   Conclusion: These results suggest that the nigrostriatal dopaminergic pathway have important modulating role on chronic pain.

  12. The ultrastructural alterations in rat corneas with experimentally-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Take, G.; Karabay, G.; Erdogan, D.; Duyar, I.

    2006-01-01

    To examine the ultrastructural changes of rat corneas in streptozotocin (STZ) induced diabetes mellitus and the and the follow-up insulin treatment. Sprague-Dawley type rats were used for experimental procedures during the period from January to April 2003 at Baskent University, Ankara, Turkey. Rats were studied in four groups: group 1: controls, group 2 sham controls (single dose IV sodium citrate); group 3 STZ-induced diabetes mellitus (Single dose 45mg/kg STZ intravenously), group 4: diabetes mellitus + insulin treatment (8U/day). We observed degenerative changes in the epithelial layer, stromal keratocytes and endothelial cells in diabetic group. In contrast, the corneal layers have revealed positive alterations in the insulin-treated group. The statistical analysis, showed significant narrowing in the epithelial layer in the diabetic group (p0.02), whereas thickening was observed in the epithelial basement membrane and Descemet's membrane (p=0.002). It was determined that that diabetes mellitus causes degenerative changes in cornea, which are positively influenced by short-term insulin treatment. (author)

  13. Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

    Science.gov (United States)

    Capelozzi, Marco A; Leick-Maldonado, Edna A; Parra, Edwin R; Martins, Mílton A; Tibério, Iolanda F L C; Capelozzi, Vera L

    2007-05-14

    Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

  14. Experimental chaotic quantification in bistable vortex induced vibration systems

    Science.gov (United States)

    Huynh, B. H.; Tjahjowidodo, T.

    2017-02-01

    The study of energy harvesting by means of vortex induced vibration systems has been initiated a few years ago and it is considered to be potential as a low water current energy source. The energy harvester is realized by exposing an elastically supported blunt structure under water flow. However, it is realized that the system will only perform at a limited operating range (water flow) that is attributed to the resonance phenomenon that occurs only at a frequency that corresponds to the fluid flow. An introduction of nonlinear elements seems to be a prominent solution to overcome the problem. Among many nonlinear elements, a bistable spring is known to be able to improve the harvested power by a vortex induced vibrations (VIV) based energy converter at the low velocity water flows. However, it is also observed that chaotic vibrations will occur at different operating ranges that will erratically diminish the harvested power and cause a difficulty in controlling the system that is due to the unpredictability in motions of the VIV structure. In order to design a bistable VIV energy converter with improved harvested power and minimum negative effect of chaotic vibrations, the bifurcation map of the system for varying governing parameters is highly on demand. In this study, chaotic vibrations of a VIV energy converter enhanced by a bistable stiffness element are quantified in a wide range of the governing parameters, i.e. damping and bistable gap. Chaotic vibrations of the bistable VIV energy converter are simulated by utilization of a wake oscillator model and quantified based on the calculation of the Lyapunov exponent. Ultimately, a series of experiments of the system in a water tunnel, facilitated by a computer-based force-feedback testing platform, is carried out to validate the existence of chaotic responses. The main challenge in dealing with experimental data is in distinguishing chaotic response from noise-contaminated periodic responses as noise will smear

  15. Experimental investigation of cavitation induced air release

    Science.gov (United States)

    Kowalski, Karoline; Pollak, Stefan; Hussong, Jeanette

    Variations in cross-sectional areas may lead to pressure drops below a critical value, such that cavitation and air release are provoked in hydraulic systems. Due to a relatively slow dissolution of gas bubbles, the performance of hydraulic systems will be affected on long time scales by the gas phase. Therefore predictions of air production rates are desirable to describe the system characteristics. Existing investigations on generic geometries such as micro-orifice flows show an outgassing process due to hydrodynamic cavitation which takes place on time scales far shorter than diffusion processes. The aim of the present investigation is to find a correlation between global, hydrodynamic flow characteristics and cavitation induced undissolved gas fractions generated behind generic flow constrictions such as an orifice or venturi tube. Experimental investigations are realised in a cavitation channel that enables an independent adjustment of the pressure level upstream and downstream of the orifice. Released air fractions are determined by means of shadowgraphy imaging. First results indicate that an increased cavitation activity leads to a rapid increase in undissolved gas volume only in the choking regime. The frequency distribution of generated gas bubble size seems to depend only indirectly on the cavitation intensity driven by an increase of downstream coalescence events due to a more densely populated bubbly flow.

  16. Changes in thermal nociceptive responses in dairy cows following experimentally induced Esherichia coli mastitis

    DEFF Research Database (Denmark)

    Rasmussen, Ditte B.; Fogsgaard, Katrine; Røntved, Christine Maria

    2011-01-01

    Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS......) in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables....

  17. Experimentally induced spermatophore production and immune responses reveal a trade-off in crickets

    OpenAIRE

    Angela M. Kerr; Susan N. Gershman; Scott K. Sakaluk

    2010-01-01

    The energetic demands of the immune system and reproduction are often high and can lead to trade-offs between these 2 life-history traits. In decorated crickets, Gryllodes sigillatus, much of a male's reproductive effort is devoted to calling, and to the synthesis of a spermatophylax, a large, gelatinous, non--sperm-containing mass forming part of the spermatophore and consumed by the female after mating. We employed a reciprocal design in which we experimentally induced an immune response in...

  18. Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

    Science.gov (United States)

    Ghazizadeh, Vahid; Nazıroğlu, Mustafa

    2014-09-01

    Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

  19. Endovascular treatment of experimentally induced aneurysms in rabbits using stents: a feasibility study

    International Nuclear Information System (INIS)

    Hans, F.J.; Thiex, R.; Gilsbach, J.M.; Krings, T.; Moeller-Hartmann, W.; Dreeskamp, H.; Stein, K.P.; Meetz, A.; Thron, A.; Pfeffer, J.; Scherer, K.; Brunn, A.

    2003-01-01

    Although Guglielmi detachable coil (GDC) systems have been generally accepted for treatment of intracranial aneurysms, primary stenting of aneurysms using porous stents or implantation of coils after stent placement remains experimental. Testing of these new methods requires an animal model which imitates human aneurysms in size, configuration and neck morphology. We assessed in detail the technical requirements of and steps for transfemoral stent treatment of experimentally induced aneurysms at the top of the brachiocephalic trunk in rabbits. We created aneurysms in ten rabbits by distal ligation and intraluminal digestion of the right common carotid artery with elastase. We treated five animals with porous stents alone, and five with stents plus coiling via the meshes of the stent, which permitted dense packing of coils. No complications related to the procedures occurred. In all animals, even in those treated solely with porous stents, total occlusion of the aneurysm was achieved. Our animal model can be suitable for testing the biocompatibility and occlusion rate of new methods and devices for the treatment of experimental aneurysms. (orig.)

  20. True Triaxial Experimental Study of Rockbursts Induced By Ramp and Cyclic Dynamic Disturbances

    Science.gov (United States)

    Su, Guoshao; Hu, Lihua; Feng, Xiating; Yan, Liubin; Zhang, Gangliang; Yan, Sizhou; Zhao, Bin; Yan, Zhaofu

    2018-04-01

    A modified rockburst testing system was utilized to reproduce rockbursts induced by ramp and cyclic dynamic disturbances with a low-intermediate strain rate of 2 × 10-3-5 × 10-3 s-1 in the laboratory. The experimental results show that both the ramp and cyclic dynamic disturbances play a significant role in inducing rockbursts. In the tests of rockbursts induced by a ramp dynamic disturbance, as the static stress before the dynamic disturbance increases, both the strength of specimens and the kinetic energy of the ejected fragments first increase and then decrease. In the tests of rockbursts induced by a cyclic dynamic disturbance, there exists a rockburst threshold of the static stress and the dynamic disturbance amplitude, and the kinetic energy of the ejected fragments first increases and then decreases as the cyclic dynamic disturbance frequency increases. The main differences between rockbursts induced by ramp dynamic disturbances and those induced by cyclic dynamic disturbances are as follows: the rockburst development process of the former is characterized by an impact failure feature, while that of the latter is characterized by a fatigue failure feature; the damage evolution curve of the specimen of the former has a leap-developing form with a significant catastrophic feature, while that of the latter has an inverted S-shape with a remarkable fatigue damage characteristic; the energy mechanism of the former involves the ramp dynamic disturbance giving extra elastic strain energy to rocks, while that of the latter involves the cyclic dynamic disturbance decreasing the ultimate energy storage capacity of rocks.

  1. Combined experimental and numerical investigation of energy harness utilizing vortex induced vibration over half cylinder using piezoelectric beams

    Science.gov (United States)

    Ahmed, Md. Tusher; Hossain, Md. Tanver; Rahman, Md. Ashiqur

    2017-06-01

    Energy harvesting technology has the ability to create self-powered electronic systems that do not rely on battery power for their operation. Wind energy can be converted into electricity via a piezoelectric transducer during the air flow over a cylinder. The vortex-induced vibration over the cylinder causes the piezoelectric beam to vibrate. Thus useful electric energy at the range 0.2-0.3V is found which can be useful for self-powering small electronic devices. In the present study, prototypes of micro-energy harvester with a shape of 65 mm × 37 mm × 0.4 mm are developed and tested for airflow over D-shaped bluff body for diameters of 15, 20 and 28mm in an experimental setup consisting of a long wind tunnel of 57cm × 57cm with variable speeds of the motor for different flow velocities and the experimental setup is connected at the downstream where flow velocity is the maximum. Experimental results show that the velocity and induced voltage follows a regular linear pattern. A maximum electrical potential of 140 mV for velocity of 1.1 ms-1 at a bluff body diameter of 15 mm is observed in the energy harvester that can be applied in many practical cases for self-powering electronic devices. The simulation of this energy harvesting phenomena is then simulated using COMSOLE multi-physics. Diameter of the bluff bodies as well as flow velocity and size of cantilever beam are varied and the experimental findings are found to be in good agreement with the simulated ones. The simulations along with the experimental data show the possibility of generating electricity from vortex induced vibration and can be applied in many practical cases for self-powering electronic devices.

  2. Effect of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    P. A. Virych

    2017-05-01

    Full Text Available The development of modern organic chemistry and molecular modeling technologies simplify the search for potential inhibitors of various receptor systems and biological processes. The one of the directions is the development of analgesics of broad spectrum and low toxicity. It is important to search for inhibitors of the kinin-kallikrein system that regulates many functions: inflammation, pain, carcinogenesis, vascular tone, smooth muscle contraction and other. Derivatives of 3-substituted 1,4-benzodiazepine-2-ones have a unique spatial conformation that allows one to simulate β-structures of bioactive peptides. The functional activity of compounds is determined by properties of their peripheral chemical radicals. We analyzed the effect of 3-substituted 1,4-benzodiazepin-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction and relaxation of the stomach in the presence of calcium channel blockers: verapamil (1 μM, gadolinium (300 μM and 2-aminoethyl diphenylborinate (0.1 μM. The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in incubation solution were 10–6 M. Data processing on dynamics of contraction was performed according to the method of Burdyha and Kosterin. Compounds MX-1775 and MX-1925 reduced maximal normalized rate (Vn of bradykinin-induced smooth muscle contraction in the presence of Gd3+ by 21.2% and 31.0% respectively. Compound MX-1925 increased Vn of relaxation by 11.6%. A similar effect is typical for MX-2011, where there is an increase by 34.6%. In the presence of verapamil this compound additionally decreased Vn contraction by 20.5%. Substances MX-1775, MX-2004 and MX-1925 restored maximal normalized rate of relaxation to original values of bradykinin-induced contraction. In the presence of 2-aminoethyldiphenylborinate MX-1775 additionally reduced Vn of contractions by 7.5%. 3-substituted 1,4-benzo­diazepine-2-ones did not change the maximal

  3. Effects of drugs and ionic variations on contractions of rat smooth ...

    African Journals Online (AJOL)

    The result of this suggests that as membrane depolarisation increases contraction in Rat Vas Deferens smooth muscle declined, while Verapamil and Nifedipine were more sensitive in blocking K+ than Ach and NA induced contractions. Keywords: Smooth muscle, Ileum, Stomach strip, Vas deferens, Contractions, Rat.

  4. The effects of experimental pain and induced optimism on working memory task performance.

    Science.gov (United States)

    Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

    2016-07-01

    Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found

  5. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

  6. Experimentally induced mastitis and metritis modulate soy bean derived isoflavone biotransformation in diary cows.

    Science.gov (United States)

    Kowalczyk-Zieba, I; Woclawek-Potocka, I; Piskula, M K; Piotrowska-Tomala, K K; Boruszewska, D; Bah, M M; Siemieniuch, M J; Skarzynski, D J

    2011-12-01

    The present study compared the changes in isoflavone (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cows with induced mastitis and metritis after feeding with soy bean. Sixteen cows were divided into four groups: control for mastitis group, cows with induced mastitis group, control for metritis group, and cows with induced metritis group. All cows were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on HPLC system. β-Glucuronidase activity in the blood plasma of cows was measured by fluorometric method. In the blood plasma of cows with induced mastitis and metritis, we found considerably higher concentrations and time-dependent increase in isoflavone metabolites (equol and para-ethyl-phenol) with reference to cyclic cows (P < 0.05). Moreover, we noticed significant decrease of genistein in the blood plasma of the cows with induced metritis compared with control cows (P < 0.05). In addition, in the blood plasma of the cows with induced metritis, we found an increase in β-glucuronidase activity compared with control cows (P < 0.05). In conclusion, health status of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the cows. Experimentally induced mastitis and metritis increased isoflavone absorption, biotransformation and metabolism. Therefore, we suggest that cows with induced mastitis and metritis are more exposed to active isoflavone metabolite actions than healthy cows. Copyright © 2011. Published by Elsevier Inc.

  7. The effect of preferred music genre selection versus preferred song selection on experimentally induced anxiety levels.

    Science.gov (United States)

    Walworth, Darcy DeLoach

    2003-01-01

    The purpose of this study was to investigate the differences of experimentally induced anxiety levels reached by subjects listening to no music (n = 30), subjects listening to music selected by the experimenter from the subject's preferred genre or artist listed as relaxing (n = 30), and subjects listening to a specific song they listed as relaxing (n = 30). Subjects consisted of 90 individuals, male and female, randomly assigned to one of the three groups mentioned above. Subjects in either music group filled out a questionnaire prior to participating in the study indicating their preference of music used for relaxation purposes. Subjects in Experimental Group 1 marked their preferred genres and/or artists, and Experimental Group 2 marked specific songs used for relaxation purposes. While the experimenter hypothesized subjects in Experimental Group 2 would show less anxiety than both the control group and Experimental Group 1, there were no significant differences found between the 2 music groups in anxiety levels reached. However, there was a statistically significant difference between the no music control group and both music groups in the anxiety level reached by subjects. Subjects listening to music, both songs chosen by the experimenter and subject selected songs, showed significantly less anxiety than subjects not listening to music.

  8. PETER. I. AZIBA * and OKUNOLA M. C.l

    African Journals Online (AJOL)

    Femi Olaleye

    The Vas Deferens showed unstable contraction in depolarised medium. The result of this suggests that as membrane depolarisation increases contraction in Rat Vas Deferens smooth muscle declined, while Verapamil and Nifedipine were more sensitive in blocking K+ than Ach and NA induced contractions. Afr. J. Biomed.

  9. Experimental investigation of cavitation induced air release

    Directory of Open Access Journals (Sweden)

    Kowalski Karoline

    2017-01-01

    Full Text Available Variations in cross-sectional areas may lead to pressure drops below a critical value, such that cavitation and air release are provoked in hydraulic systems. Due to a relatively slow dissolution of gas bubbles, the performance of hydraulic systems will be affected on long time scales by the gas phase. Therefore predictions of air production rates are desirable to describe the system characteristics. Existing investigations on generic geometries such as micro-orifice flows show an outgassing process due to hydrodynamic cavitation which takes place on time scales far shorter than diffusion processes. The aim of the present investigation is to find a correlation between global, hydrodynamic flow characteristics and cavitation induced undissolved gas fractions generated behind generic flow constrictions such as an orifice or venturi tube. Experimental investigations are realised in a cavitation channel that enables an independent adjustment of the pressure level upstream and downstream of the orifice. Released air fractions are determined by means of shadowgraphy imaging. First results indicate that an increased cavitation activity leads to a rapid increase in undissolved gas volume only in the choking regime. The frequency distribution of generated gas bubble size seems to depend only indirectly on the cavitation intensity driven by an increase of downstream coalescence events due to a more densely populated bubbly flow.

  10. Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons: vesicular versus non-vesicular release of GABA

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, Gert Helge; Schousboe, A

    1993-01-01

    differences in the mode of action of the two depolarizing stimuli were reflected in the properties of the increase in [Ca++]i elicited by 55 mM K+ and 100 microM glutamate, respectively. The K(+)-induced increase in [Ca++]i was reduced by both verapamil and Ca(++)-free media whereas the corresponding...... neurotransmitter glutamate (100 microM). Both depolarizing stimuli exerted prompt increases in the release of preloaded [3H]GABA as well as in [Ca++]i. However, the basic properties of transmitter release and the increase in [Ca++]i under a variety of conditions were different during stimulation with K...... was also reduced by organic (verapamil) and inorganic (Co++) Ca++ channel blockers but was insensitive to the GABA transport inhibitor SKF 89976A. In contrast, the second phase was less sensitive to nocodazole and Ca++ channel antagonists but could be inhibited by SKF 89976A. The glutamate-induced [3H...

  11. Lymphocytes contribute to biliary injury and fibrosis in experimental xenobiotic-induced cholestasis

    International Nuclear Information System (INIS)

    Joshi, Nikita; Kopec, Anna K.; Cline-Fedewa, Holly; Luyendyk, James P.

    2017-01-01

    The etiology of chronic bile duct injury and fibrosis in patients with autoimmune cholestatic liver diseases is complex, and likely involves immune cells such as lymphocytes. However, most models of biliary fibrosis are not autoimmune in nature. Biliary fibrosis can be induced experimentally by prolonged exposure of mice to the bile duct toxicant alpha-naphthylisothiocyanate (ANIT). We determined whether lymphocytes contributed to ANIT-mediated biliary hyperplasia and fibrosis in mice. Hepatic accumulation of T-lymphocytes and increased serum levels of anti-nuclear-autoantibodies were evident in wild-type mice exposed to ANIT (0.05% ANIT in chow). This occurred alongside bile duct hyperplasia and biliary fibrosis. To assess the role of lymphocytes in ANIT-induced biliary fibrosis, we utilized RAG1 −/− mice, which lack T- and B-lymphocytes. ANIT-induced bile duct injury, indicated by increased serum alkaline phosphatase activity, was reduced in ANIT-exposed RAG1 −/− mice compared to ANIT-exposed wild-type mice. Despite this reduction in biliary injury, ANIT-induced bile duct hyperplasia was similar in wild-type and RAG1 −/− mice. However, hepatic induction of profibrogenic genes including COL1A1, ITGβ6 and TGFβ2 was markedly attenuated in ANIT-exposed RAG1 −/− mice compared to ANIT-exposed wild-type mice. Peribiliary collagen deposition was also reduced in ANIT-exposed RAG1 −/− mice. The results indicate that lymphocytes exacerbate bile duct injury and fibrosis in ANIT-exposed mice without impacting bile duct hyperplasia.

  12. Saturation of the laser-induced narrowband coherent synchrotron radiation process: Experimental observation at a storage ring

    Science.gov (United States)

    Hosaka, M.; Yamamoto, N.; Takashima, Y.; Szwaj, C.; Le Parquier, M.; Evain, C.; Bielawski, S.; Adachi, M.; Zen, H.; Tanikawa, T.; Kimura, S.; Katoh, M.; Shimada, M.; Takahashi, T.

    2013-02-01

    We study the efficiency limitation affecting laser-induced coherent synchrotron radiation (CSR) at high laser power. Experiments are made on the UVSOR-II storage ring in conditions of narrowband terahertz CSR emission. While, at moderate power, CSR power increases quadratically with laser power, a noticeable decrease in efficiency and eventually a decrease in CSR power is observed experimentally at high power. Details of the underlying process are analyzed numerically. As the saturation effect depends almost instantaneously on the laser intensity, the saturation occurs locally in longitudinal space. This has important consequences on the modulation pattern induced on the electron bunch.

  13. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  14. Human experimental anxiety: actual public speaking induces more intense physiological responses than simulated public speaking.

    Science.gov (United States)

    Zuardi, Antonio Waldo; Crippa, José Alexandre de Souza; Hallak, Jaime Eduardo Cecílio; Gorayeb, Ricardo

    2013-01-01

    a) To perform a systematic and meta-analytic review to verify whether the Simulated Public Speaking Task (SPST) leads to a greater increase in self-rated anxiety than in physiological correlates of anxiety; and b) to compare the results obtained with the SPST with an actual public speaking task involving healthy volunteers. a) The PubMed and ISI Web of Knowledge databases were searched for studies involving the SPST prior to 2012. Eleven publications were eligible and provided data from 143 healthy volunteers for meta-analysis; b) 48 university students without somatic or psychiatric disorders were divided into three experimental groups of 16 subjects to undergo one of the following: SPST, real-world public speaking task (real-world), and control situation (control). The meta-analysis showed that the SPST induced a significant increase in the Visual Analogue Mood Scale (VAMS) anxiety factor, but no significant increases in systolic blood pressure or heart rate. The empirical study showed that the real-world public speaking task increased heart rate, systolic blood pressure and diastolic blood pressure significantly more than the control and SPST conditions. These results suggest that real public speaking might be better than SPST in inducing experimental anxiety.

  15. Foraminiferal survival after long-term in situ experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-11-01

    Anoxia was successfully induced in four benthic chambers installed at 24 m depth on the northern Adriatic seafloor from 9 days to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerTM Green method was applied and calcareous and agglutinated foraminifera were analyzed. Numerous individuals were found living at all sampling times and at all sampling depths (to 5 cm), supported by a ribosomal RNA analysis that revealed that certain benthic foraminifera were active after 10 months of anoxia. The results show that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulfides. However, foraminiferal standing stocks decrease with sampling time in an irregular manner. A large difference in standing stock between two cores sampled under initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after one month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in cores sampled after 2 months of anoxia to then attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulfides but rather due to a continuous diminution of labile organic matter.

  16. Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

    Science.gov (United States)

    Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

    2010-07-01

    The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

  17. Effects of normal saline and selenium-enriched hot spring water on experimentally induced rhinosinusitis in rats.

    Science.gov (United States)

    Kim, Dong-Hyun; Yeo, Sang Won

    2013-01-01

    This prospective, randomized, and controlled study examined the effects of normal saline and selenium-enriched hot spring water on experimentally induced rhinosinusitis in rats. The study comprised two control groups (untreated and saline-treated) and three experimental groups of Sprague Dawley rats. The experimental groups received an instillation of lipopolysaccharide (LPS) only, LPS+normal saline (LPS/saline), or LPS+selenium-enriched hot spring water (LPS/selenium). Histopathological changes were identified using hematoxylin-eosin staining. Leakage of exudate was identified using fluorescence microscopy. Microvascular permeability was measured using the Evans blue dye technique. Expression of the Muc5ac gene was measured using reverse transcription-polymerase chain reaction. Mucosal edema and expression of the Muc5ac gene were significantly lower in the LPS/saline group than in the LPS group. Microvascular permeability, mucosal edema, and expression of the Muc5ac gene were significantly lower in the LPS/selenium group than in the LPS group. Mucosal edema was similar in the LPS/selenium group and LPS/saline group, but capillary permeability and Muc5ac expression were lower in the LPS/selenium group. This study shows that normal saline and selenium-enriched hot spring water reduce inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Effects of experimentally induced intestinal obstruction on the electrolyte profile in dogs

    International Nuclear Information System (INIS)

    Dar, E.M.; Khan, M.A.; Mehmood, A.K.

    2004-01-01

    This study was conducted to quantitatively asses the changes in serum electrolyte profile after experimentally induced upper and lower intestinal obstruction in dogs. Ten dogs of either sex ranging in weight from 20-25 Kg were selected. After thorough physical examination, de-worming and vaccination they were randomly divided into 3 groups. Groups A and B comprised of four animals each while group C had two animals. After preparing the operation site, upper intestinal obstruction was induced in animals of group A and lower intestinal obstruction was induced in all animals of group B through mid line laparotomy under general anesthesia. Animals of group C were kept as control without induction of any obstruction. Proper post-operative care was given to the operated animals. Blood samples were collected from all animals at an interval of 24 hours and evaluated to observe changes in serum sodium, potassium and chloride levels. The results of this study showed marked decline in electrolyte levels in animals of both groups A and B, however this decline was more severe and rapid in group A than group B, while group c acted normally. It can be concluded that upper intestinal obstruction is more fatal in its consequences than lower intestinal obstruction, which is relatively less dangerous in producing its ill effects. (author)

  19. Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma.

    Science.gov (United States)

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

    2015-01-01

    Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg(-1) of 5 % dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30-300 mgkg(-1)), acetazolamide (5 mgkg(-1)), and normal saline (10 mLkg(-1)) per os were measured. IOPs were also monitored in chronic glaucoma in rabbits (induced by 1 % prednisolone acetate drops, 12 hourly for 21 days) after treatments with the same doses of HIE, acetazolamide, and normal saline for 2 weeks. The anti-oxidant property of the extract was assessed by assaying for glutathione levels in the aqueous humour. Glutamate concentration in the vitreous humour was also determined using ELISA technique. Histopathological assessment of the ciliary bodies was made. The extract significantly reduced intraocular pressure (p ≤ 0.05-0.001) in acute and chronic glaucoma, preserved glutathione levels and glutamate concentration (p ≤ 0.01-0.001). Histological assessment of the ciliary body showed a decrease in inflammatory infiltration in the extract and acetazolamide-treated group compared with the normal saline-treated group. The aqueous whole plant extract of Heliotropium indicum has ocular hypotensive, anti-oxidant and possible neuro-protective effects, which therefore underscore its plausible utility as an anti-glaucoma drug with further investigation.

  20. Mechanism of blue-light-induced plasma-membrane depolarization in etiolated cucumber hypocotyls

    Science.gov (United States)

    Spalding, E. P.; Cosgrove, D. J.

    1992-01-01

    A large, transient depolarization of the plasma membrane precedes the rapid blue-light (BL)-induced growth suppression in etiolated seedlings of Cucumis sativus L. The mechanism of this voltage transient was investigated by applying inhibitors of ion channels and the plasma-membrane H(+)-ATPase, by manipulating extracellular ion concentrations, and by measuring cell input resistance and ATP levels. The depolarizing phase was not affected by Ca(2+)-channel blockers (verapamil, La3+) or by reducing extracellular free Ca2+ by treatment with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). However, these treatments did reduce the rate of repolarization, indicating an inward movement of Ca2+ is involved. No effects of the K(+)-channel blocker tetraethylammonium (TEA+) were detected. Vanadate and KCN, used to inhibit the H(+)-ATPase, reduced or completely inhibited the BL-induced depolarization. Levels of ATP increased by 11-26% after 1-2 min of BL. Input resistance of trichrome cells, measured with double-barreled microelectrodes, remained constant during the onset of the depolarization but decreased as the membrane voltage became more positive than -90 mV. The results indicate that the depolarization mechanism initially involves inactivation of the H(+)-ATPase with subsequent transient activation of one or more types of ion channels.

  1. Theoretical and experimental studies of single event effect induced by atmospheric muons on nano-metric technologies

    International Nuclear Information System (INIS)

    Li Cavoli, P.

    2016-01-01

    This study concerns the domain of the microelectronics. It consists in the study of the impact of the 3D morphology of the energy deposit on the Single Event Effect (SEE) modeling, induced by atmospheric muons. Over a first phase, the approach has consisted in the modeling of the energy deposit induced by protons in nano-metric volumes. For that purpose the use of the Monte Carlo code GEANT4 has allowed us to simulate and stock in a database the tracks characteristics of the energy deposit induced by protons. Once the approach validated for the protons, simulations of the energy deposit induced by muons have been realized. A CCD camera has been used in order to measure the radiative atmospheric environment and to constrain the modeling of the energy deposit induced by muons. This study highlights and quantify the contribution of the radial distribution of the energy deposit induced by protons in nano-metric volumes for the SEE prediction. On the other hand, the study shows that the contribution of the radial distribution of the energy deposit induced by muons in nano-metric volumes has a negligible impact on the SEE modeling. It will be interesting to realize measurements of the energy deposit induced by muons in nano-metric technologies under particle accelerator. This will allow to bring experimental data still nonexistent necessary to the development of new physical models more accurate on the modeling of the energy deposit induced by muons. (author)

  2. Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

    Science.gov (United States)

    Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

    2017-09-01

    To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

  3. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

    2010-10-01

    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  4. Lipid metabolism in streptozotocin induced experimental diabetes and it’s correction with niacin-oxyethylidendiphosphonatogermanate

    Directory of Open Access Journals (Sweden)

    N. V. Kresyun

    2017-08-01

    Full Text Available Introduction. The development of approaches for effective control of diabetes-induced deterioration of lipid metabolism and plasma glucose level could be implemented by the applying of germanium-contained biologically active substances. Among others such compound as niacin – oxyethylidendiphosphonatogermanate (MIGU-4 should be mentioned, which is able to correct effectively the lipid layers of liver mitochondrial membranes on models of streptozotocin – induced diabetes. Aim. To investigate the dynamic changes of the total cholesterol, total phospholipids level along with their molar ratio; fractions of phospholipids of both erythrocyte membranes and liver mitochondria membranes in experimental diabetes mellitus and to investigate the mentioned indices under conditions of complex correction by MIGU-4 and insulin. Materials and Methods. Diabetes was induced in male Wistar rats with streptozotocin injection (50.0 mg/kg., i. p.. ED50 of MIGU-4 (25.0 mg/kg, i. p. was used. Cellular membranes were obtained from erythrocytes, and mitochondrial membranes were obtained through differential centrifugation of liver tissue. Lipid extracts were isolated from 1 g of erythrocyte mass and from 200 mg of liver tissue; phospholipids fractionation was carried out by method of ascending one-dimensional thin-layer chromatography. Content of certain phospholipids was estimated by method of spots “burning out” using the 72 % chloride acid at 200 0С up to their complete bleaching with the consequent determination of lipids phosphate. The level of total phospholipids was calculated by summing up all fractions content. Results. The total cholesterol level substantially elevated along with the decreasing of phospholipids content in both erythrocyte and mitochondrial membranes obtained from liver tissue in two weeks after experimental streptozotocin diabetes induction in rats. It resulted in an increase of the cholesterol/ phospholipids ratio. These changes

  5. Confabulation versus experimentally induced false memories in Korsakoff patients.

    Science.gov (United States)

    Van Damme, Ilse; d'Ydewalle, Géry

    2010-09-01

    The present study focuses on both the clinical symptom of confabulation and experimentally induced false memories in patients suffering from Korsakoff's syndrome. Despite the vast amount of case studies of confabulating patients and studies investigating false memories in the Deese-Roediger-McDermott (DRM) paradigm, the nature of Korsakoff patients' confabulatory behaviour and its association with DRM false memories have been rarely examined. Hence, the first aim of the present study was to evaluate confabulatory responses in a large sample of chronic Korsakoff patients and matched controls by means of the Dalla Barba Confabulation Battery. Second, the association between (provoked) confabulation and the patients' DRM false recognition performance was investigated. Korsakoff patients mainly confabulated in response to questions about episodic memory and questions to which the answer was unknown. A positive association was obtained between confabulation and the tendency to accept unstudied distractor words as being old in the DRM paradigm. On the other hand, there was a negative association between confabulation and false recognition of critical lures. The latter could be attributed to the importance of strategic retrieval at delayed memory testing.

  6. Hypolipidemic Effect of Fenugreek Seeds and its Comparison with Atorvastatin on Experimentally Induced Hyperlipidemia

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, M. S. [R.N.T. Medical College, Udaipur (India). Dept. of Physiology; Choudhary, P. R. [C.U. Shah Medical College, Surendranagr (India). Dept. of Physiology

    2014-08-15

    Objective: To determine the hypolipidemic effect of fenugreek (Methi) seeds and its comparison with atorvastatin on experimentally induced hyperlipidemia in rabbits. Study Design: Experimental interventional study. Place and Duration of Study: Department of Physiology, Dr. S. N. Medical College, Jodhpur, Rajasthan, India, from April 2012 to March 2013. Methodology: Twenty, 1 - 2 years old albino rabbits of European Strains were randomly divided into two groups of 10 rabbits each. All were fed pure cholesterol (0.5 g/kg body weight/day) for 4 weeks to induce hyperlipidemia. Group-I comprised of 10 hyperlipidemic rabbits which were fed normal (regular) diet supplemented with 2 ml aqueous emulsified fenugreek seeds powder (500 mg/kg body weight/day) for 4 weeks. Group-II comprised of 10 hyperlipidemic rabbits, which were fed normal (regular) diet supplemented with 2 ml aqueous emulsion of atorvastatin (0.5 mg/kg body weight/day) for 4 weeks. Fasting blood samples were collected two times during experimental period at weeks (4 and 8) and analyzed for serum total cholesterol and triglycerides, using semi-automated chemistry analyzer. HDL-C was determined by precipitation method and LDL-C and VLDL-C were estimated by Friedewalds formula. LDL/HDL ratio and TG/HDL ratios were also calculated. The significance of difference in mean values of both groups (lipid profile) was assessed by independent student's t-test. Results: Atorvastatin showed a more potent hypolipidemic activity. It reduced serum total cholesterol, TG, LDL and VLDLcholesterol, and the atherogenic index (LDL-C/HDL-C; p < 0.001) highly significantly as compared to fenugreek. There was a significant increase of HDL-C (p < 0.01) in group-I as compared to group-II. Conclusion: Fenugreek and atorvastatin both have hypolipidemic activity in rabbits but atorvastatin is more potent than fenugreek seeds powder. (author)

  7. Hypolipidemic Effect of Fenugreek Seeds and its Comparison with Atorvastatin on Experimentally Induced Hyperlipidemia

    International Nuclear Information System (INIS)

    Sharma, M. S.; Choudhary, P. R.

    2014-01-01

    Objective: To determine the hypolipidemic effect of fenugreek (Methi) seeds and its comparison with atorvastatin on experimentally induced hyperlipidemia in rabbits. Study Design: Experimental interventional study. Place and Duration of Study: Department of Physiology, Dr. S. N. Medical College, Jodhpur, Rajasthan, India, from April 2012 to March 2013. Methodology: Twenty, 1 - 2 years old albino rabbits of European Strains were randomly divided into two groups of 10 rabbits each. All were fed pure cholesterol (0.5 g/kg body weight/day) for 4 weeks to induce hyperlipidemia. Group-I comprised of 10 hyperlipidemic rabbits which were fed normal (regular) diet supplemented with 2 ml aqueous emulsified fenugreek seeds powder (500 mg/kg body weight/day) for 4 weeks. Group-II comprised of 10 hyperlipidemic rabbits, which were fed normal (regular) diet supplemented with 2 ml aqueous emulsion of atorvastatin (0.5 mg/kg body weight/day) for 4 weeks. Fasting blood samples were collected two times during experimental period at weeks (4 and 8) and analyzed for serum total cholesterol and triglycerides, using semi-automated chemistry analyzer. HDL-C was determined by precipitation method and LDL-C and VLDL-C were estimated by Friedewalds formula. LDL/HDL ratio and TG/HDL ratios were also calculated. The significance of difference in mean values of both groups (lipid profile) was assessed by independent student's t-test. Results: Atorvastatin showed a more potent hypolipidemic activity. It reduced serum total cholesterol, TG, LDL and VLDLcholesterol, and the atherogenic index (LDL-C/HDL-C; p < 0.001) highly significantly as compared to fenugreek. There was a significant increase of HDL-C (p < 0.01) in group-I as compared to group-II. Conclusion: Fenugreek and atorvastatin both have hypolipidemic activity in rabbits but atorvastatin is more potent than fenugreek seeds powder. (author)

  8. Trust and Cheating in Sri Lanka: The Role of Experimentally-Induced Emotions about Tsunam

    OpenAIRE

    Pierluigi Conzo

    2014-01-01

    Through a field experiment in Sri Lanka I analyze the role of experimentally-induced memories of 2004 tsunami on behavior in a trust game in which personal notions of cheating are elicited. Microfinance borrowers were randomly assigned to a treatment (control) group consisting in watching a video about the calamity before (after) playing. Trust game participants were asked how much to receive (return) in order not to (make the counterpart) feel cheated; in a survey they selected whether the v...

  9. Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient.

    Science.gov (United States)

    Patel, Maulik R; Bhalodia, Yagnik S; Pathak, Nimish L; Patel, Maulik S; Suthar, Kunal; Patel, Nilesh; Golwala, Dharmesh K; Jivani, Nurudin P

    2013-12-12

    In the traditional medicine, Cynodon dactylon (Linn.) is used in asthma, but scientific studies to provide evidence for medicinal uses are sparse. Thus this study was undertaken to provide evidence for medicinal use in asthma as a bronchodilator, and to identify active ingredient(s). In vivo, acetylcholine (Ach)-induced bronchospasm was conducted in guinea pig while isolated rat tracheal strip was suspended in organ bath to measure the concentration response curve using multichannel data acquisition system. The chloroform extract of Cynodon dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs, similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and high K+-induced contraction of rat tracheal strip, similar to atropine and verapamil respectively, suggesting antimuscarinic and calcium channel blocking (CCB) activities, which were confirmed by right ward shifting of CCh and Ca(+2) concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory activity was confirmed by potentiation of isoprenaline-induced inhibitory response, similar to papaverine. Densitometry analyses led to the identification of scopoletin as an active ingredient. Effectively, it significantly inhibited high K+, and Ca(+2) induced contractile response, similar to verapamil. The phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of potentiation of isoprenaline-induced inhibitory response, similar to papaverine. These results suggest that the bronchodilator activity of CECD is partly due to presence of scopoletin, and mediated possibly through CCB and PDE inhibition.

  10. Depolarization by K+ and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons: vesicular versus non-vesicular release of GABA

    DEFF Research Database (Denmark)

    Belhage, B; Hansen, G H; Schousboe, A

    1993-01-01

    was also reduced by organic (verapamil) and inorganic (Co++) Ca++ channel blockers but was insensitive to the GABA transport inhibitor SKF 89976A. In contrast, the second phase was less sensitive to nocodazole and Ca++ channel antagonists but could be inhibited by SKF 89976A. The glutamate-induced [3H...

  11. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    International Nuclear Information System (INIS)

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10 5 /well). Cells treated with GnRH Ca ++ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca ++ -free media prevented the action of GnRH. GnRH caused a rapid efflux of 45 Ca ++ . Both GnRH-stimulated 45 Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect 45 Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE 2 and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca ++ does not regulate LH release; (2) GnRH elevates intracellular Ca ++ by opening both voltage sensitive and receptor mediated Ca ++ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release

  12. Immunologic responses in corn snakes (Pantherophis guttatus) after experimentally induced infection with ferlaviruses.

    Science.gov (United States)

    Neul, Annkatrin; Schrödl, Wieland; Marschang, Rachel E; Bjick, Tina; Truyen, Uwe; von Buttlar, Heiner; Pees, Michael

    2017-04-01

    OBJECTIVE To measure immunologic responses of snakes after experimentally induced infection with ferlaviruses. ANIMALS 42 adult corn snakes (Pantherophis guttatus) of both sexes. PROCEDURES Snakes were inoculated intratracheally with genogroup A (n = 12), B (12), or C (12) ferlavirus (infected groups) or cell-culture supernatant (6; control group) on day 0. Three snakes from each infected group were euthanized on days 4, 16, 28, and 49, and 3 snakes from the control group were euthanized on day 49. Blood samples were collected from live snakes on days -6 (baseline), 4, 16, 28, and 49. Hematologic tests were performed and humoral responses assessed via hemagglutination-inhibition assays and ELISAs. Following euthanasia, gross pathological and histologic evaluations and virus detection were performed. RESULTS Severity of clinical signs of and immunologic responses to ferlavirus infection differed among snake groups. Hematologic values, particularly WBC and monocyte counts, increased between days 4 and 16 after infection. A humoral response was identified between days 16 and 28. Serum IgM concentrations increased from baseline earlier than IgY concentrations, but the IgY relative increase was higher at the end of the study. The hemagglutination-inhibition assay revealed that the strongest reactions in all infected groups were against the strain with which they had been infected. Snakes infected with genogroup A ferlavirus had the strongest immune response, whereas those infected with genogroup B had the weakest responses. CONCLUSIONS AND CLINICAL RELEVANCE Results of this experimental study suggested that the ferlavirus strain with the highest virulence induced the weakest immune response in snakes.

  13. Evaluation of safety and protective effects of Potentilla fulgens root extract in experimentally induced diarrhoea in mice

    Directory of Open Access Journals (Sweden)

    V. Tangpu

    2014-06-01

    Methods: The protective effects of P. fulgens root extract was investigated against experimentally induced diarrhoea in mice, using four experimental models, i.e. measurement of faecal output, castor oil model, prostaglandin E2 (PGE2 enteropooling assay and gastrointestinal transit test. The safety assessment of root extract was done in mice on the basis of general signs and symptoms of toxicity, food water intake and mortality of animals following their treatment with various doses of extract (100 and ndash;3200 mg/kg. In addition, the serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, cholesterol and total protein of experimental mice were also monitored to assess the toxicity of root extract. Results: In the safety assessment studies, P. fulgens root extract did not showed any visible signs of toxicity, but mortality was observed in a single animal at 3200 mg/kg dose of extract. The extract also did not showed any adverse effects on the studied serum parameters of experimental animals. In the antidiarrhoeal tests, administration of 800 mg/kg dose of extract to mice showed 50% protection from diarrhoea evoked by castor oil. In addition, the extract also showed 29.27% reduction in PGE2-induced intestinal secretion as compared to 30.31% recorded for loperamide, a standard anti-diarrhoeal drug. Conclusions: The results of this study indicate that P. fulgens root extract possesses significant anti-diarrhoeal properties. Therefore, the roots of this plant can be an effective traditional medicine for the protection from diarrhoea. [J Intercult Ethnopharmacol 2014; 3(3.000: 103-108

  14. An Experimental Study on the Wind-Induced Response of Variable Message Signs

    Directory of Open Access Journals (Sweden)

    Debbie Meyer

    2017-11-01

    Full Text Available Variable message sign (VMS systems are widely used in motorways to provide traffic information to motorists. Such systems are subjected to wind-induced structural vibration that can lead to damage due to fatigue. The limited information that is available on the safe wind design of VMS motivated a large scale testing that was conducted at the wall of wind (WOW Experimental Facility at Florida International University (FIU. One of the objectives of the present study was to experimentally assess the wind-induced force coefficients on VMS of different geometries and utilize these results to provide improved design guidelines. A comprehensive range of VMS geometries was tested, and mean normal and lateral force coefficients, in addition to the twisting moment coefficient and eccentricity ratio, were determined using the measured data for each model, for wind directions of 0° and 45°. The results confirmed that the mean drag coefficient on a prismatic VMS is smaller than the value of 1.7 suggested by American Association of State Highway and Transportation Officials (AASHTO. An alternative to this value is presented in the form of a design matrix with coefficients ranging from 0.98 to 1.28, depending on the aspect and depth ratio of the VMS. Furthermore, results indicated that the corner modification on a VMS with chamfered edges demonstrated a reduction in the drag coefficient compared to sharper edges. Finally, the dynamic loading effects were considered by evaluating the gust effect factor, using the ASCE 7 formulations, for various VMS weights and geometries. The findings revealed a wide range of possible gust effect factors, both above and below the current AASHTO specification of 1.14. Future research may include different geometries of VMS and a wider range of wind directions.

  15. Comparative study on reversal efficacy of SDZ PSC 833, cyclosporin a and verapamil on multidrug resistance in vitro and in vivo

    International Nuclear Information System (INIS)

    Watanabe, Toru; Tsuge, Harumi; Oh-Hara, Tomoko; Naito, Mikihiko; Tsuruo, Takashi

    1995-01-01

    A non-immunosuppressive cyclosporin, SDZ PSC 833 (PSC833), shows a reversal effect on multidrug resistance (MDR) by functional modulation of MDR1 gene product, P-glycoprotein. The objective of the present study was to compare the reversal efficacy of three multidrug resistance modulators, PSC833, cyclosporin A (CsA) and verapamil (Vp). PSC833 has approximately 3-10-fold greater potency than CsA and Vp with respect to the restoring effect on reduced accumulation of doxorubicin (ADM) and vincristine (VCR) in ADM-resistant K562 myelogenous leukemia cells (K562/ADM) in vitro and also on the sensitivity of K562/ADM to ADM and VCR in in vitro growth inhibition. The in vivo efficacy of a combination of modifiers (PSC833 and CsA: 50 mg/kg, Vp 100 mg/kg administered p.o. 4 h before the administration of anticancer drugs) with anticancer drugs (ADM 2.5 mg/kg i.p., Q4D days 1, 5 and 9, VCR 0.05 mg/kg i.p., QD days 1-5) was tested in ADM-resistant P388-bearing mice. PSC833 significantly enhanced the increase in life span by more than 80%, whereas CsA and Vp enhanced by less than 50%. This reversal potency, which exceeded that of CsA and Vp, was confirmed by therapeutic experiments using colon adenocarcinoma 26-bearing mice. These results demonstrated that PSC833 has significant potency to reverse MDR in vitro and in vivo, suggesting that PSC833 is a good candidate for reversing multidrug resistance in clinical situations. (orig.)

  16. Experimental Protoporphyria: Effect of Bile Acids on Liver Damage Induced by Griseofulvin

    Directory of Open Access Journals (Sweden)

    María del Carmen Martinez

    2015-01-01

    Full Text Available The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA, dehydrocholic (DHA, chenodeoxycholic, or ursodeoxycholic (URSO. The administration of Gris alone increased the activities of glutathione reductase (GRed, superoxide dismutase (SOD, alkaline phosphatase (AP, gamma glutamyl transpeptidase (GGT, and glutathione-S-transferase (GST, as well as total porphyrins, glutathione (GSH, and cytochrome P450 (CYP levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

  17. Experimentally studied laser fluorescence method for remote sensing of plant stress situation induced by improper plants watering

    Directory of Open Access Journals (Sweden)

    Yu. V. Fedotov

    2014-01-01

    Full Text Available Stressful situations of plants can be caused by a lack of nutrients; mechanical damages; diseases; low or high temperatures; lack of illumination; insufficient or excess humidity of the soil; soil salinization; soil pollution by oil products or heavy metals; the increased acidity of the soil; use of pesticides, herbicides, insecticides, etc.At early stages it is often difficult to detect seemingly that the plants are in stressful situations caused by adverse external factors. However, the fluorescent analysis potentially allows detection of the stressful situations of plants by deformation of laser-induced fluorescence spectra. The paper conducts experimental investigations to learn the capabilities of the laser fluorescent method to monitor plant situations at 532nm wavelength of fluorescence excitation in the stressful situations induced by improper watering (at excess of moisture in the soil and at a lack of moisture.Researches of fluorescence spectra have been conducted using a created laboratory installation. As a source to excite fluorescence radiation the second harmonica of YAG:Nd laser is used. The subsystem to record fluorescence radiation is designed using a polychromator and a highly sensitive matrix detector with the amplifier of brightness.Experimental investigations have been conducted for fast-growing and unpretentious species of plants, namely different sorts of salad.Experimental studies of laser-induced fluorescence spectra of plants for 532nm excitement wavelength show that the impact of stressful factors on a plant due to the improper watering, significantly distorts a fluorescence spectrum of plants. Influence of a stressful factor can be shown as a changing profile of a fluorescence spectrum (an identifying factor, here, is a relationship of fluorescence intensities at two wavelengths, namely 685 nm and 740 nm or (and as a changing level of fluorescence that can be the basis for the laser method for monitoring the plant

  18. Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

    OpenAIRE

    Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

    2012-01-01

    Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 ?g collagen. ...

  19. Animal model of atherosclerosis using rabbit experimentally induced by combination of X-ray and hypercholesterolemia

    International Nuclear Information System (INIS)

    Ishiyama, Tomotoshi; Sawai, Takashi; Okuma, Tsuneo; Mori, Shozo

    1995-01-01

    An attempt was made to prepare an animal model of atherosclerosis similar to human lesions. The experimental animals were male Japanese white rabbits weighting about 2 kg. Hypercholesterolemia was experimentally induced by giving a 1% cholesterol diet. Four weeks later, a single dose of 45 Gy was delivered to the femur to produce vascular changes. Soon after irradiation, immunohistochemical examination revealed the adhesion and invasion of macrophages to endothelial cells, followed by accumulation of foam cells and thickness of the intimal plaques. Three months after irradiation, these thickened plaques became fibrotic, calcified, and necrotic. The tunica media was thinned and the internal elastic lamella was destroyed. Irradiated arteries exhibited not only severe narrowing of the lumen but also aneurysmal dilation and the lesions of the irradiated arteries resembled human atherosclerosis. In conclusion, the atherosclerotic model produced by combining experimental hypercholesterolemia and X-ray irradiaiton may serve as a useful model for studies on atherosclerosis because it can be prepared with no need of complicated or time-consuming procedures. (N.K.)

  20. Experimental Research of Reliability of Plant Stress State Detection by Laser-Induced Fluorescence Method

    Directory of Open Access Journals (Sweden)

    Yury Fedotov

    2016-01-01

    Full Text Available Experimental laboratory investigations of the laser-induced fluorescence spectra of watercress and lawn grass were conducted. The fluorescence spectra were excited by YAG:Nd laser emitting at 532 nm. It was established that the influence of stress caused by mechanical damage, overwatering, and soil pollution is manifested in changes of the spectra shapes. The mean values and confidence intervals for the ratio of two fluorescence maxima near 685 and 740 nm were estimated. It is presented that the fluorescence ratio could be considered a reliable characteristic of plant stress state.

  1. Impact of field-induced quantum confinement on the onset of tunneling field-effect transistors: Experimental verification

    Energy Technology Data Exchange (ETDEWEB)

    Smets, Quentin, E-mail: quentin.smets@imec.be; Verreck, Devin; Heyns, Marc M. [Imec, Kapeldreef 75, 3001 Heverlee (Belgium); KULeuven, 3000 Leuven (Belgium); Verhulst, Anne S.; Martens, Koen; Lin, Han Chung; Kazzi, Salim El; Simoen, Eddy; Collaert, Nadine; Thean, Aaron [Imec, Kapeldreef 75, 3001 Heverlee (Belgium); Raskin, Jean-Pierre [ICTEAM, Université catholique de Louvain, 1348 Louvain-la-Neuve (Belgium)

    2014-11-17

    The Tunneling Field-Effect Transistor (TFET) is a promising device for future low-power logic. Its performance is often predicted using semiclassical simulations, but there is usually a large discrepancy with experimental results. An important reason is that Field-Induced Quantum Confinement (FIQC) is neglected. Quantum mechanical simulations show FIQC delays the onset of Band-To-Band Tunneling (BTBT) with hundreds of millivolts in the promising line-TFET configuration. In this letter, we provide experimental verification of this delayed onset. We accomplish this by developing a method where line-TFET are modeled using highly doped MOS capacitors (MOS-CAP). Using capacitance-voltage measurements, we demonstrate AC inversion by BTBT, which was so far unobserved in MOS-CAP. Good agreement is shown between the experimentally obtained BTBT onset and quantum mechanical predictions, proving the need to include FIQC in all TFET simulations. Finally, we show that highly doped MOS-CAP is promising for characterization of traps deep into the conduction band.

  2. Impact of field-induced quantum confinement on the onset of tunneling field-effect transistors: Experimental verification

    International Nuclear Information System (INIS)

    Smets, Quentin; Verreck, Devin; Heyns, Marc M.; Verhulst, Anne S.; Martens, Koen; Lin, Han Chung; Kazzi, Salim El; Simoen, Eddy; Collaert, Nadine; Thean, Aaron; Raskin, Jean-Pierre

    2014-01-01

    The Tunneling Field-Effect Transistor (TFET) is a promising device for future low-power logic. Its performance is often predicted using semiclassical simulations, but there is usually a large discrepancy with experimental results. An important reason is that Field-Induced Quantum Confinement (FIQC) is neglected. Quantum mechanical simulations show FIQC delays the onset of Band-To-Band Tunneling (BTBT) with hundreds of millivolts in the promising line-TFET configuration. In this letter, we provide experimental verification of this delayed onset. We accomplish this by developing a method where line-TFET are modeled using highly doped MOS capacitors (MOS-CAP). Using capacitance-voltage measurements, we demonstrate AC inversion by BTBT, which was so far unobserved in MOS-CAP. Good agreement is shown between the experimentally obtained BTBT onset and quantum mechanical predictions, proving the need to include FIQC in all TFET simulations. Finally, we show that highly doped MOS-CAP is promising for characterization of traps deep into the conduction band

  3. Experimental evaluation of the pressure and temperature dependence of ion-induced nucleation.

    Science.gov (United States)

    Munir, Muhammad Miftahul; Suhendi, Asep; Ogi, Takashi; Iskandar, Ferry; Okuyama, Kikuo

    2010-09-28

    An experimental system for the study of ion-induced nucleation in a SO(2)/H(2)O/N(2) gas mixture was developed, employing a soft x-ray at different pressure and temperature levels. The difficulties associated with these experiments included the changes in physical properties of the gas mixture when temperature and pressure were varied. Changes in the relative humidity (RH) as a function of pressure and temperature also had a significant effect on the different behaviors of the mobility distributions of particles. In order to accomplish reliable measurement and minimize uncertainties, an integrated on-line control system was utilized. As the pressure decreased in a range of 500-980 hPa, the peak concentration of both ions and nanometer-sized particles decreased, which suggests that higher pressure tended to enhance the growth of particles nucleated by ion-induced nucleation. Moreover, the modal diameters of the measured particle size distributions showed a systematic shift to larger sizes with increasing pressure. However, in the temperature range of 5-20 °C, temperature increases had no significant effects on the mobility distribution of particles. The effects of residence time, RH (7%-70%), and SO(2) concentration (0.08-6.7 ppm) on ion-induced nucleation were also systematically investigated. The results show that the nucleation and growth were significantly dependent on the residence time, RH, and SO(2) concentration, which is in agreement with both a previous model and previous observations. This research will be inevitable for a better understanding of the role of ions in an atmospheric nucleation mechanism.

  4. High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens

    Science.gov (United States)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Gazzotti, Valeria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The aims of this study was the safety and the efficacy of High Intensity Laser Therapy (HILT) on chronic degenerative tenosynovitis. We have effectuated the histological evaluation and seroassay (C reactive protein) on 18 chickens affect by chronic degenerative tenosynovitis experimentally induced. We have been employed a Nd:YAG laser pulsed wave; all irradiated subjects received the same total energy (270 Joule) with a fluence of 7,7 J/cm2 and intensity of 10,7 W/cm2. The histological findings revealed a distinct reduction of the mineralization of the choral matrix, the anti-inflammatory effect of the laser, the hyperplasia of the synoviocytes and ectasia of the lymphatic vessels.

  5. Experimental study of stress-induced localized transformation plastic zones in tetragonal zirconia polycrystalline ceramics

    International Nuclear Information System (INIS)

    Sun, Q.; Zhao, Z.; Chen, W.; Qing, X.; Xu, X.; Dai, F.

    1994-01-01

    Stress-induced martensitic transformation plastic zones in ceria-stabilized tetragonal zirconia polycrystalline ceramics (Ce-TZP), under loading conditions of uniaxial tension, compression, and three-point bending, are studied by experiments. The transformed monoclinic phase volume fraction distribution and the corresponding plastic strain distribution and the surface morphology (surface uplift) are measured by means of moire interferometry, Raman microprobe spectroscopy, and the surface measurement system. The experimental results from the above three kinds of specimens and methods consistently show that the stress-induced transformation at room temperature of the above specimen is not uniform within the transformation zone and that the plastic deformation is concentrated in some narrow band; i.e., macroscopic plastic flow localization proceeds during the initial stage of plastic deformation. Flow localization phenomena are all observed in uniaxial tension, compression, and three-point bending specimens. Some implications of the flow localization to the constitutive modeling and toughening of transforming thermoelastic polycrystalline ceramics are explored

  6. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo [Hallym University College of Medicine, Seoul (Korea, Republic of); Park, Moon Hyang [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  7. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    International Nuclear Information System (INIS)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo; Park, Moon Hyang

    2001-01-01

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  8. Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis

    Directory of Open Access Journals (Sweden)

    Klaas Ilka C

    2011-05-01

    Full Text Available Abstract Background Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables. Methods Seven Danish Holstein-Friesian cows were kept in tie-stalls, where the E. coli associated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts and E. coli counts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control and days 1, 2, 3, 6 and 10 after experimental induction of mastitis. Results All clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found. Conclusions Changes in behavioral responses coincide with peaks in local and systemic signs of E

  9. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    International Nuclear Information System (INIS)

    Yang, Cuiping; Zhang, Tianhong; Li, Zheng; Xu, Liang; Liu, Fei; Ruan, Jinxiu; Liu, Keliang; Zhang, Zhenqing

    2013-01-01

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10 −5 to 2.85 × 10 −5 cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C max ) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC 0–12 h ) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C max and AUC of aconitine. • P

  10. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  11. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

    International Nuclear Information System (INIS)

    Giavazzi, R.; Garofalo, A.; Bani, M.R.; Abbate, M.; Ghezzi, P.; Boraschi, D.; Mantovani, A.; Dejana, E.

    1990-01-01

    This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies

  12. Assessment of efficacy of polaprezinc suppositories against radiation-induced rectal disorders using an experimental rat model

    International Nuclear Information System (INIS)

    Doi, Hiroshi; Kamikonya, Norihiko; Takada, Yasuhiro

    2009-01-01

    The purpose/objective of this study was to establish an experimental rat model and examine the efficacy of polaprezinc suppositories against radiation-induced rectal disorders. Female Wister rats (6 weeks old) were used in the present study. The rats were divided into three groups. Group A was irradiated and medicated with polaprezinc suppositories. Group B was irradiated without any medication. Group C had no irradiation or medication. The rat was taped by the tail in the vertical position under anesthesia. Lead shielding was used to cover the rats except the area of the lower pelvis. They were irradiated at 22 Gy by a single fraction. Polaprezinc suppositories were inserted daily into the rat anus for 7 days after irradiation. All rats were evaluated by colonoscopy on the 7th day after irradiation, sacrificed on the 10th day, and evaluated for mucosal damage. In the clinical findings, the endoscopic findings, and the histological findings, the rats not administered polaprezinc suppositories tended to show more severe mucosal damage but there were no significant differences. Our study showed that this model was a useful experimental rat model for radiation-induced rectal disorders and polaprezinc suppositories demonstrated good efficacy against radiation proctitis. (author)

  13. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  14. Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

    Science.gov (United States)

    Al-Awadi, F M; Srikumar, T S; Anim, J T; Khan, I

    2001-05-01

    Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

  15. 224Ra and 226Ra experimentally induced dental changes in rats

    International Nuclear Information System (INIS)

    Reichart, P.A.; Althoff, J.; Eckhardt, W.; Rippel, W.

    1979-01-01

    Sprague-Dawley rats received intragastrically a single dose of 226 Ra or 224 Ra once weekly for 21 weeks. During this period the animals of both groups were thus exposed to comparable doses. After 12 weeks, a shortening of the maxillary incisors was observed, and this progressed during the course of the 55-week experiment. Radiologically, a loss of pulpal transparency and an apical irregular opacity in the maxillary incisors were demonstrable. Histologically, dysplastic changes of the maxillary incisors and multiple resorptions at the cemento-enamel junction of the molars were seen. The observed alterations were more pronounced in the 226 Ra group than in the 224 Ra treated group. The experimentally induced resorptions were comparable to those observed in patients who had incorporated 224 Ra or 226 Ra. Clinical, radiological, histological, γspecrometrical, and autoradiographical findings, as well as dose-estimations, are described. (author)

  16. Laser-induced interactions

    International Nuclear Information System (INIS)

    Green, W.R.

    1979-01-01

    This dissertation discusses some of the new ways that lasers can be used to control the energy flow in a medium. Experimental and theoretical considerations of the laser-induced collision are discussed. The laser-induced collision is a process in which a laser is used to selectively transfer energy from a state in one atomic or molecular species to another state in a different species. The first experimental demonstration of this process is described, along with later experiments in which lasers were used to create collisional cross sections as large as 10 - 13 cm 2 . Laser-induced collisions utilizing both a dipole-dipole interaction and dipole-quadrupole interaction have been experimentally demonstrated. The theoretical aspects of other related processes such as laser-induced spin-exchange, collision induced Raman emission, and laser-induced charge transfer are discussed. Experimental systems that could be used to demonstrate these various processes are presented. An experiment which produced an inversion of the resonance line of an ion by optical pumping of the neutral atom is described. This type of scheme has been proposed as a possible method for constructing VUV and x-ray lasers

  17. Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses. I. Experimental. Part 1

    International Nuclear Information System (INIS)

    Stuart, B.C.; Herman, S.; Perry, M.D.

    1994-12-01

    The authors report extensive laser-induced damage threshold measurements on pure and multilayer dielectrics at 1053 and 526 mm for pulse durations, τ, ranging from 140 fs to 1 ns. Qualitative differences in the morphology of damage and a departure from the diffusion-dominated τ 1/2 scaling indicate that damage results from plasma formation and ablation for τ≤10 ps and from conventional melting and boiling for τ>50 ps. A theoretical model based on electron production via multiphoton ionization, Joule heating, and collisional (avalanche) ionization is in good agreement with both the pulsewidth and wavelength scaling of experimental results

  18. Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

    Science.gov (United States)

    Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

    2015-01-01

    The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

  19. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    Science.gov (United States)

    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  20. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  1. Effect of Gmelina arborea Roxb in experimentally induced inflammation and nociception

    Directory of Open Access Journals (Sweden)

    Yogesh A Kulkarni

    2013-01-01

    Full Text Available Background: Gmelina arborea Roxb (Verbenaceae, also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE and methanol extracts (ME of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01 and 8.2 ± 1.24 (P < 0.01 respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3% as compared to ME (77.9% in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.

  2. Mechanisms controlling the oxygen consumption in experimentally induced hypochloremic alkalosis in calves.

    Science.gov (United States)

    Cambier, Carole; Clerbaux, Thierry; Amory, Hélène; Detry, Bruno; Florquin, Sandra; Marville, Vincent; Frans, Albert; Gustin, Pascal

    2002-01-01

    . It may be concluded that, despite reduced oxygen delivery, oxygen consumption is maintained during experimentally induced hypochloremic alkalosis in healthy 10-30 day old calves.

  3. HYPOLIPEDEMIC EFFECT OF CYNODON DACTYLON ON HISTOPATHOLOGICAL STUDY AND DNA FRAGMENTATION ANALYSIS IN EXPERIMENTALLY INDUCED HYPERCHOLESTEREMIC RATS

    OpenAIRE

    C. Selva Kumar

    2011-01-01

    Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of Ayurvedic herbal formulation Cynodon dactylon (Bermuda grass) on histopathological study and DNA fragmentation analysis in experimentally induced hypercholesteremic rats. Four groups of rats were employed namely control, hypercholesterolemia rats (4% Cholesterol+1% cholic acid), Cynodon dactylon treatment in hypercholesteremic rats and Cynodon dactylon alone treated rats. Re...

  4. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    International Nuclear Information System (INIS)

    Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

    2009-01-01

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  5. In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Flynn, J.C.; Kong, Y.C.

    1991-01-01

    In several experimental autoimmune diseases, including experimental autoimmune thyroiditis (EAT), vaccination with attenuated autoantigen-specific T cells has provided protection against subsequent induction of disease. However, the mechanism(s) of vaccination-induced suppression remains to be clarified. Since the authors have previously shown that suppression generated by pretreatment with mouse thyroglobulin (MTg) or thyroid-stimulating hormone in EAT is mediated by CD4+, not CD8+, suppressor T cells, they examined the role of T cell subsets in vaccination-induced suppression of EAT. Mice were vaccinated with irradiated, MTg-primed, and MTg-activated spleen cells and then challenged. Pretreatment with these cells suppressed EAT induced by immunization with MTg and adjuvant, but not by adoptive transfer of thyroiditogenic cells, suggesting a mechanism of afferent suppression. The activation of suppressor mechanisms did not require CD8+ cells, since mice depleted of CD8+ cells before vaccination showed reduced EAT comparable to control vaccinated mice. Furthermore, depletion of either the CD4+ or the CD8+ subset after vaccination did not significantly abrogate suppression. However, suppression was eliminated by the depletion of both CD4+ and CD8+ cells in vaccinated mice. These results provide evidence for the cooperative effects of CD4+ and CD8+ T cells in vaccination-induced suppression of EAT

  6. Transport rankings of non-steroidal antiinflammatory drugs across blood-brain barrier in vitro models.

    Directory of Open Access Journals (Sweden)

    Iveta Novakova

    Full Text Available The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line for proper data comparison.

  7. Complexity of MRI induced heating on metallic leads: Experimental measurements of 374 configurations

    Directory of Open Access Journals (Sweden)

    Mendoza Gonzalo

    2008-03-01

    Full Text Available Abstract Background MRI induced heating on PM leads is a very complex issue. The widely varying results described in literature suggest that there are many factors that influence the degree of heating and that not always are adequately addressed by existing testing methods. Methods We present a wide database of experimental measurements of the heating of metallic wires and PM leads in a 1.5 T RF coil. The aim of these measurements is to systematically quantify the contribution of some potential factors involved in the MRI induced heating: the length and the geometric structure of the lead; the implant location within the body and the lead path; the shape of the phantom used to simulate the human trunk and its relative position inside the RF coil. Results We found that the several factors are the primary influence on heating at the tip. Closer locations of the leads to the edge of the phantom and to the edge of the coil produce maximum heating. The lead length is the other crucial factor, whereas the implant area does not seem to have a major role in the induced temperature increase. Also the lead structure and the geometry of the phantom revealed to be elements that can significantly modify the amount of heating. Conclusion Our findings highlight the factors that have significant effects on MRI induced heating of implanted wires and leads. These factors must be taken into account by those who plan to study or model MRI heating of implants. Also our data should help those who wish to develop guidelines for defining safe medical implants for MRI patients. In addition, our database of the entire set of measurements can help those who wish to validate their numerical models of implants that may be exposed to MRI systems.

  8. Experimental study of microwave-induced thermoacoustic imaging

    Science.gov (United States)

    Jacobs, Ryan T.

    Microwave-Induced Thermoacoustic Imaging (TAI) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub-microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in tissue samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost alternative to MRI and early breast cancer detection methods. This work describes the implementation of a thermoacoustic experiment using a 5 kW peak power microwave source.

  9. Polymer-coated compliant receivers for intact laser-induced forward transfer of thin films: experimental results and modelling

    Science.gov (United States)

    Feinaeugle, Matthias; Horak, Peter; Sones, Collin L.; Lippert, Thomas; Eason, Rob W.

    2014-09-01

    In this study, we investigate both experimentally and numerically laser-induced forward transfer (LIFT) of thin films to determine the role of a thin polymer layer coating the receiver with the aim of modifying the rate of deceleration and reduction of material stress preventing intact material transfer. A numerical model of the impact phase during LIFT shows that such a layer reduces the modelled stress. The evolution of stress within the transferred deposit and the substrate as a function of the thickness of the polymer layer, the transfer velocity and the elastic properties of the polymer are evaluated. The functionality of the polymer layer is verified experimentally by LIFT printing intact 1- m-thick bismuth telluride films and polymeric light-emitting diode pads onto a layer of 12-m-thick polydimethylsiloxane and 50-nm-thick poly(3,4-ethylenedioxythiophene) blended with poly(styrenesulfonate) (PEDOT:PSS), respectively. Furthermore, it is demonstrated experimentally that the introduction of such a compliant layer improves adhesion between the deposit and its substrate.

  10. In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Baudouin, Christophe; Denoyer, Alexandre; Desbenoit, Nicolas; Hamm, Gregory; Grise, Alice

    2012-12-01

    Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fractalkine receptor and their respective mRNAs. Benzalkonium in vitro induced apoptosis, oxidative stress, and fractalkine expression and inhibited the protective chemokine SDF-1 and Bcl2, also inducing a sustained intraocular pressure (IOP) increase, with dramatic apoptosis of trabecular cells and reduction of aqueous outflow. MS imaging showed that BAK could access the TM at measurable levels after repeated instillations. BAK enhances all characteristics of TM degeneration typical of glaucoma-trabecular apoptosis, oxidative stress, induction of inflammatory chemokines-and causes degeneration in acute experimental conditions, potentially mimicking long-term accumulation. BAK was also shown to access the TM after repeated instillations. These findings support the hypothesis that antiglaucoma medications, through toxicity of their preservative, may cause further long-term trabecular degeneration and therefore enhance outflow resistance, reducing the impact of IOP-lowering agents.

  11. Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.

    Science.gov (United States)

    Reinero, Carol R; Decile, Kendra C; Byerly, Jenni R; Berghaus, Roy D; Walby, William E; Berghaus, Londa J; Hyde, Dallas M; Schelegle, Edward S; Gershwin, Laurel J

    2005-07-01

    To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma. 6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA). A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs. Mean +/- SE eosinophil percentages in BALF when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/- 1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%), compared with values for the control treatment (63.6 +/- 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments. Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGA-specific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma.

  12. Experimental Gestational Diabetes Mellitus Induces Blunted Vasoconstriction and Functional Changes in the Rat Aorta

    Directory of Open Access Journals (Sweden)

    Cecilia Tufiño

    2014-01-01

    Full Text Available Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD induced gestational diabetes mellitus (GDM, so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy with standard (SD or hypercaloric (HD diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P<0.05 versus SD in intact (e+ but not in endothelium-free (e− vessels. Losartan reduced GDM but not SD e− vasoconstriction (P<0.01 versus SD. AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P<0.05 versus SD. Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations.

  13. Analgesic effects of intramuscular administration of meloxicam in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis.

    Science.gov (United States)

    Cole, Gretchen A; Paul-Murphy, Joanne; Krugner-Higby, Lisa; Klauer, Julia M; Medlin, Scott E; Keuler, Nicholas S; Sladky, Kurt K

    2009-12-01

    OBJECTIVE-To evaluate the analgesic efficacy of meloxicam in parrots with experimentally induced arthritis, with extent of weight bearing and rotational perch walking used as outcome measures. ANIMALS-15 adult Hispaniolan parrots (Amazona ventralis). PROCEDURES-Arthritis was experimentally induced via intra-articular injection of microcrystalline sodium urate suspension (MSU) into 1 intertarsal joint. Parrots were treated in a crossover design. Five treatments were compared as follows: meloxicam (4 dosages) at 0.05, 0.1, 0.5, and 1.0 mg/kg (IM, q 12 h, 3 times) and 0.03 mL of saline (0.9% NaCl) solution (IM, q 12 h, 3 times). The first treatment was given 6 hours following MSU administration. Lameness was assessed by use of a biomechanical perch to record weight-bearing load and a rotational perch to determine dexterity. Feces were collected to assay for occult blood. RESULTS-Parrots treated with meloxicam at 1.0 mg/kg had significantly better return to normal (baseline) weight bearing on the arthritic pelvic limb, compared with control parrots or parrots treated with meloxicam at 0.05, 0.1, and 0.5 mg/kg. All fecal samples collected from parrots following induction of arthritis and treatment with meloxicam had negative results for occult blood. CONCLUSIONS AND CLINICAL RELEVANCE-Meloxicam administered at 1.0 mg/kg, IM, every 12 hours effectively relieved arthritic pain in parrots.

  14. Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade.

    Science.gov (United States)

    Bashir, Samra; Memon, Raafia; Gilani, Anwar H

    2011-01-01

    Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr) was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01-1 mg/mL) relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K(+)-induced contractions (0.01-0.3 mg/mL), similar to verapamil, suggestive of calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03-0.1 mg/mL) rightward shift in the Ca(++) concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100-300 mg/kg) protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders.

  15. Immunologic and hematologic responses in ponies with experimentally induced Strongylus vulgaris infection.

    Science.gov (United States)

    Bailey, M; Martin, S C; Lloyd, S

    1989-08-01

    Immunologic and hematologic responses were examined in 4 ponies with experimentally induced Strongylus vulgaris infection and in 5 helminth-free ponies. Two ponies were inoculated with 200 larvae and 2 were inoculated with 700 larvae of S vulgaris and then were reinoculated with the same numbers of larvae 34 weeks later. Initial response of the ponies inoculated with S vulgaris was S vulgaris antigen-induced lymphocyte response that developed 1.5 to 3 weeks after inoculation and did not persist. Development of antigen-reactive lymphocytes was followed sequentially by a biphasic complement-fixing antibody response, then biphasic eosinophilia. Antibody titer to S vulgaris antigen was higher in ponies inoculated with 700 larvae, compared with that in ponies given 200 larvae of S vulgaris. Also, the second peak in antibody titer and in absolute number of eosinophils was observed earlier in ponies inoculated with 700 larvae, compared with ponies inoculated with 200 S vulgaris larvae, and subsided before or from about 24 weeks after inoculation. The prepatent period for S vulgaris infection was 24 to 25 weeks. After reinoculation with S vulgaris, a degree of increased lymphocyte responsiveness was apparent but, by 17 weeks after reinoculation, only the primary peak in the absolute number of eosinophils indicated an anamnestic response. Essentially, antibody was not detectable after reinoculation.

  16. P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

    2013-12-15

    Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

  17. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

    Science.gov (United States)

    Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

    2017-12-01

    Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

  18. Experimentally induced thyrotoxicosis leads to increased connectivity in temporal lobe structures: a resting state fMRI study.

    Science.gov (United States)

    Göttlich, Martin; Heldmann, Marcus; Göbel, Anna; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

    2015-06-01

    Adult onset hyperthyroidism may impact on different cognitive domains, including attention and concentration, memory, perceptual function, language and executive function. Previous PET studies implicated changed functionality of limbic regions, the temporal and frontal lobes in hyperthyroidism, whereas it is unknown whether cognitive effects of hyperthyroidism may be due to changed brain connectivity. This study aimed to investigate the effect of experimentally induced short-term hyperthyroidism thyrotoxicosis on resting-state functional connectivity using functional magnetic resonance imaging. Twenty-nine healthy male right-handed subjects were examined twice, once prior and once after 8 weeks of oral administration of 250 μg levothyroxine per day. Resting-state fMRI was subjected to graph-theory based analysis methods to investigate whole-brain intrinsic functional connectivity. Despite a lack of subjective changes noticed by the subjects significant thyrotoxicosis was confirmed in all subjects. This induced a significant increase in resting-state functional connectivity specifically in the rostral temporal lobes (0.05 FDR corrected at the cluster level), which is caused by an increased connectivity to the cognitive control network. The increased connectivity between temporal poles and the cognitive control network shown here under experimental conditions supports an important function of thyroid hormones in the regulation of paralimbic structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Placebo effect of an inert gel on experimentally induced leg muscle pain

    Directory of Open Access Journals (Sweden)

    James G Hopker

    2010-11-01

    Full Text Available James G Hopker1, Abigail J Foad2, Christopher J Beedie2, Damian A Coleman2, Geoffrey Leach11Centre for Sports Studies, University of Kent, Chatham, Kent, UK; 2Department of Sports Science, Tourism and Leisure, Canterbury Christ Church University, Canterbury, Kent, UKPurpose: This study examined the therapeutic effects of an inert placebo gel on experimentally induced muscle pain in a sports therapy setting. It aimed to investigate the degree to which conditioned analgesia, coupled with an expectation of intervention, was a factor in subsequent analgesia.Methods: Participants were sixteen male and eight female sports therapy students at a UK University. With institutional ethics board approval and following informed consent procedures, each was exposed to pain stimulus in the lower leg in five conditions, ie, conditioning, prebaseline, experimental (two placebo gel applications, and postbaseline. In conditioning trials, participants identified a level of pain stimulus equivalent to a perceived pain rating of 6/10. An inert placebo gel was then applied to the site with the explicit instruction that it was an analgesic. Participants were re-exposed to the pain stimulus, the level of which, without their knowledge, had been decreased, creating the impression of an analgesic effect resulting from the gel. In experimental conditions, the placebo gel was applied and the level of pain stimulus required to elicit a pain rating of 6/10 recorded.Results: Following application of the placebo gel, the level of pain stimulus required to elicit a pain rating of 6/10 increased by 8.2%. Application of the placebo gel significantly decreased participant’s perceptions of muscle pain (P = 0.001.Conclusion: Subjects’ experience and expectation of pain reduction may be major factors in the therapeutic process. These factors should be considered in the sports therapeutic environment.Keywords: conditioning, expectation, perception, positive belief, sports therapy

  20. A three-layer model of self-assembly induced surface-energy variation experimentally extracted by using nanomechanically sensitive cantilevers

    International Nuclear Information System (INIS)

    Zuo Guomin; Li Xinxin

    2011-01-01

    This research is aimed at elucidating surface-energy (or interfacial energy) variation during the process of molecule-layer self-assembly on a solid surface. A quasi-quantitative plotting model is proposed and established to distinguish the surface-energy variation contributed by the three characteristic layers of a thiol-on-gold self-assembled monolayer (SAM), namely the assembly-medium correlative gold/head-group layer, the chain/chain interaction layer and the tail/medium layer, respectively. The data for building the model are experimentally extracted from a set of correlative thiol self-assemblies in different media. The variation in surface-energy during self-assembly is obtained by in situ recording of the self-assembly induced nanomechanical surface-stress using integrated micro-cantilever sensors. Based on the correlative self-assembly experiment, and by using the nanomechanically sensitive self-sensing cantilevers to monitor the self-assembly induced surface-stressin situ, the experimentally extracted separate contributions of the three layers to the overall surface-energy change aid a comprehensive understanding of the self-assembly mechanism. Moreover, the quasi-quantitative modeling method is helpful for optimal design, molecule synthesis and performance evaluation of molecule self-assembly for application-specific surface functionalization.

  1. Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine.

    Science.gov (United States)

    Jurkiewicz, Neide Hyppolito; da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Ferreira Verde, Luciana; Drawanz Pereira, Janaina; Mendes Sobrinho, Cairo; Soubhi Smaili, Soraya; Caricati-Neto, Afonso; Miranda-Ferreira, Regiane; Jurkiewicz, Aron

    2012-09-15

    Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Reduced myocardial 18F-FDG uptake after calcium channel blocker administration. Initial observation for a potential new method to improve plaque detection

    International Nuclear Information System (INIS)

    Gaeta, Chiara; Flotats, Albert; Artigas, Carles; Deportos, Jordi; Geraldo, Llanos; Carrio, Ignasi; Fernandez, Yolanda; Pavia, Javier

    2011-01-01

    Physiological glucose uptake by the myocardium may hamper visualization of coronary atherosclerotic plaques in 18 F-FDG PET studies. Intracellular myocardial calcium relates to glucose influx. We assessed whether administration of a calcium channel blocker such as verapamil could decrease myocardial 18 F-FDG uptake in mice. Experiments were conducted on ten male C57BL/6JOlaHsd mice. The mice were studied by 18 F-FDG PET/CT under basal conditions and after a single administration of verapamil injected 1 h prior to 18 F-FDG administration at doses of 1 mg/kg (group A, n = 5) and 20 mg/kg (group B, n = 5). PET scanning was started 60 min after injection of 18 F-FDG employing a dedicated small-animal PET/CT system (ARGUS-CT). In each mouse, post-verapamil PET images were coregistered with the basal PET images. Volumetric regions of interest (VOI) were drawn on the basal study containing the myocardium of the whole left ventricle and quantitatively compared with the same VOI applied to the post-verapamil scan. The SUV mean was used to express the mean myocardial 18 F-FDG uptake. The relative coefficient of variation (RV) between the basal and post-verapamil conditions was calculated. Verapamil administration decreased myocardial 18 F-FDG uptake in all animals. The median (range) SUV mean values in group A were 2.6 (1.6-4.1) under basal conditions and 1.7 (1.1-2.9) after verapamil administration (p = 0.043), and in group B were 1.6 (1.3-2.0) under basal conditions and 1.0 (0.9-1.4) after verapamil administration (p = 0.043). The median (range) RV values were -31% (-5%, -50%) in group A, and -37% (-10%, -51%) in group B (p = 0.6). In this animal model there was a significant reduction in 18 F-FDG uptake in the myocardium following verapamil administration. This type of intervention could facilitate the definition of coronary atherosclerotic plaque inflammation on 18 F-FDG PET scans. (orig.)

  3. Experimental evaluation of earthquake induced relay chattering

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.; Hofmayer, C.; Shteyngart, S.

    1990-01-01

    An experimental evaluation of relay performance under vibratory environments is discussed in this paper. Single frequency excitation was used for most tests. Limited tests were performed with random multifrequency inputs. The capacity of each relay was established based on a two-millisecond chatter criterion. The experimental techniques are described and the effects of parameters in controlling the relay capacity levels are illustrated with test data. A wide variation of the capacity levels was observed due to the influence of parameters related to the design of the relay and nature of the input motion. 3 refs., 15 figs

  4. Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis.

    Science.gov (United States)

    Valladares, Roberto D; Nich, Christophe; Zwingenberger, Stefan; Li, Chenguang; Swank, Katherine R; Gibon, Emmanuel; Rao, Allison J; Yao, Zhenyu; Goodman, Stuart B

    2014-09-01

    Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure. © 2013 Wiley Periodicals, Inc.

  5. L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Sachin L Badole

    Full Text Available The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg. Nicotinamide (100 mg/kg, i.p. was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o., II: diabetic control (distilled water, 10 ml/kg, p.o., III: L-glutamine (500 mg/kg, p.o. and IV: L-glutamine (1000 mg/kg, p.o.. All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

  6. The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

    Science.gov (United States)

    Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

    2016-12-01

    This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. RAE-1 expression is induced during experimental autoimmune encephalomyelitis and is correlated with microglia cell proliferation.

    Science.gov (United States)

    Djelloul, Mehdi; Popa, Natalia; Pelletier, Florence; Raguénez, Gilda; Boucraut, José

    2016-11-01

    Retinoic acid early induced transcript-1 (RAE-1) glycoproteins are ligands of the activating immune receptor NKG2D. They are known as stress molecules induced in pathological conditions. We previously reported that progenitor cells express RAE-1 in physiological conditions and we described a correlation between RAE-1 expression and cell proliferation. In addition, we showed that Raet1 transcripts are induced in the spinal cord of experimental autoimmune encephalomyelitis (EAE) mice. EAE is a model for multiple sclerosis which is accompanied by microglia proliferation and activation, recruitment of immune cells and neurogenesis. We herein studied the time course expression of the two members of the Raet1 gene family present in C57BL/6 mice, namely Raet1d and Raet1e, in the spinal cord during EAE. We report that Raet1d and Raet1e genes are induced early upon EAE onset and reach a maximal expression at the peak of the pathology. We show that myeloid cells, i.e. macrophages as well as microglia, are cellular sources of Raet1 transcripts. We also demonstrate that only Raet1d expression is induced in microglia, whereas macrophages expressed both Raet1d and Raet1e. Furthermore, we investigated the dynamics of RAE-1 expression in microglia cultures. RAE-1 induction correlated with cell proliferation but not with M1/M2 phenotypic orientation. We finally demonstrate that macrophage colony-stimulating factor (M-CSF) is a major factor controlling RAE-1 expression in microglia. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium

    International Nuclear Information System (INIS)

    Kutty, R.K.; Singh, Y.; Santostasi, G.; Krishna, G.

    1989-01-01

    Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of [14C]adenine nucleotides from hepatocytes prelabeled with [14C]-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, [14C]adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the [14C]adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death

  9. Effects of sevoflurane on ventilator induced lung injury in a healthy lung experimental model.

    Science.gov (United States)

    Romero, A; Moreno, A; García, J; Sánchez, C; Santos, M; García, J

    2016-01-01

    Ventilator-induced lung injury (VILI) causes a systemic inflammatory response in tissues, with an increase in IL-1, IL-6 and TNF-α in blood and tissues. Cytoprotective effects of sevoflurane in different experimental models are well known, and this protective effect can also be observed in VILI. The objective of this study was to assess the effects of sevoflurane in VILI. A prospective, randomized, controlled study was designed. Twenty female rats were studied. The animals were mechanically ventilated, without sevoflurane in the control group and sevoflurane 3% in the treated group (SEV group). VILI was induced applying a maximal inspiratory pressure of 35 cmH2O for 20 min without any positive end-expiratory pressure for 20 min (INJURY time). The animals were then ventilated 30 min with a maximal inspiratory pressure of 12 cmH2O and 3 cmH2O positive end-expiratory pressure (time 30 min POST-INJURY), at which time the animals were euthanized and pathological and biomarkers studies were performed. Heart rate, invasive blood pressure, pH, PaO2, and PaCO2 were recorded. The lung wet-to-dry weight ratio was used as an index of lung edema. No differences were found in the blood gas analysis parameters or heart rate between the 2 groups. Blood pressure was statistically higher in the control group, but still within the normal clinical range. The percentage of pulmonary edema and concentrations of TNF-α and IL-6 in lung tissue in the SEV group were lower than in the control group. Sevoflurane attenuates VILI in a previous healthy lung in an experimental subclinical model in rats. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Pumped storage system model and experimental investigations on S-induced issues during transients

    Science.gov (United States)

    Zeng, Wei; Yang, Jiandong; Hu, Jinhong

    2017-06-01

    Because of the important role of pumped storage stations in the peak regulation and frequency control of a power grid, pump turbines must rapidly switch between different operating modes, such as fast startup and load rejection. However, pump turbines go through the unstable S region in these transition processes, threatening the security and stability of the pumped storage station. This issue has mainly been investigated through numerical simulations, while field experiments generally involve high risks and are difficult to perform. Therefore, in this work, the model test method was employed to study S-induced security and stability issues for a pumped storage station in transition processes. First, a pumped storage system model was set up, including the piping system, model units, electrical control systems and measurement system. In this model, two pump turbines with different S-shaped characteristics were installed to determine the influence of S-shaped characteristics on transition processes. The model platform can be applied to simulate any hydraulic transition process that occurs in real power stations, such as load rejection, startup, and grid connection. On the experimental platform, the S-shaped characteristic curves were measured to be the basis of other experiments. Runaway experiments were performed to verify the impact of the S-shaped characteristics on the pump turbine runaway stability. Full load rejection tests were performed to validate the effect of the S-shaped characteristics on the water-hammer pressure. The condition of one pump turbine rejecting its load after another defined as one-after-another (OAA) load rejection was performed to validate the possibility of S-induced extreme draft tube pressure. Load rejection experiments with different guide vane closing schemes were performed to determine a suitable scheme to adapt the S-shaped characteristics. Through these experiments, the threats existing in the station were verified, the

  11. Experimentally induced masseter-pain changes masseter but not sternocleidomastoid muscle-related activity during mastication.

    Science.gov (United States)

    Pasinato, Fernanda; Santos-Couto-Paz, Clarissa C; Zeredo, Jorge Luis Lopes; Macedo, Sergio Bruzadelli; Corrêa, Eliane C R

    2016-12-01

    The aim of this study was to verify the effects of induced masseter-muscle pain on the amplitude of muscle activation, symmetry and coactivation of jaw- and neck-muscles during mastication. Twenty-eight male volunteers, mean age±SD 20.6±2.0years, participated in this study. Surface electromyography of the masseter and sternocleidomastoid (SCM) muscles was performed bilaterally during mastication of a gummy candy before and after injections of monosodium glutamate solution and isotonic saline solution. As a result, we observed a decrease in the amplitude of activation of the masseter muscle on the working side (p=0.009; d=0.34) and a reduction in the asymmetry between the working and the balancing side during mastication (p=0.007; d=0.38). No changes were observed either on the craniocervical electromyographic variables. In conclusion, experimentally induced pain reduced the masseter muscle activation on the working side, thereby reducing the physiological masseters' recruitment asymmetry between the two sides during mastication. No effects on SCM activity were detected. These results may partly explain the initial maladaptative changes underlying TMD conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Radiation induced currents in mineral-insulated cables and in pick-up coils: model calculations and experimental verification in the BR1 reactor

    Science.gov (United States)

    Vermeeren, Ludo; Leysen, Willem; Brichard, Benoit

    2018-01-01

    Mineral-insulated (MI) cables and Low-Temperature Co-fired Ceramic (LTCC) magnetic pick-up coils are intended to be installed in various position in ITER. The severe ITER nuclear radiation field is expected to lead to induced currents that could perturb diagnostic measurements. In order to assess this problem and to find mitigation strategies models were developed for the calculation of neutron-and gamma-induced currents in MI cables and in LTCC coils. The models are based on calculations with the MCNPX code, combined with a dedicated model for the drift of electrons stopped in the insulator. The gamma induced currents can be easily calculated with a single coupled photon-electron MCNPX calculation. The prompt neutron induced currents requires only a single coupled neutron-photon-electron MCNPX run. The various delayed neutron contributions require a careful analysis of all possibly relevant neutron-induced reaction paths and a combination of different types of MCNPX calculations. The models were applied for a specific twin-core copper MI cable, for one quad-core copper cable and for silver conductor LTCC coils (one with silver ground plates in order to reduce the currents and one without such silver ground plates). Calculations were performed for irradiation conditions (neutron and gamma spectra and fluxes) in relevant positions in ITER and in the Y3 irradiation channel of the BR1 reactor at SCK•CEN, in which an irradiation test of these four test devices was carried out afterwards. We will present the basic elements of the models and show the results of all relevant partial currents (gamma and neutron induced, prompt and various delayed currents) in BR1-Y3 conditions. Experimental data will be shown and analysed in terms of the respective contributions. The tests were performed at reactor powers of 350 kW and 1 MW, leading to thermal neutron fluxes of 1E11 n/cm2s and 3E11 n/cm2s, respectively. The corresponding total radiation induced currents are ranging from

  13. Postcountershock myocardial damage after pretreatment with adrenergic and calcium channel antagonists in halothane-anesthetized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Gaba, D.M.; Metz, S.; Maze, M.

    1985-05-01

    Transthoracic electric countershock can cause necrotic myocardial lesions in humans as well as experimental animals. The authors investigated the effect on postcountershock myocardial damage of pretreatment with prazosin, an alpha-1 antagonist; L-metoprolol, a beta-1 antagonist, and verapamil, a calcium channel-blocking agent. Twenty dogs were anesthetized with halothane and given two transthoracic countershocks of 295 delivered joules each after drug or vehicle treatment. Myocardial injury was quantitated 24 h following countershock by measuring the uptake of technetium-99m pyrophosphate in the myocardium. Elevated technetium-99m pyrophosphate uptake occurred in visible lesions in most dogs regardless of drug treatment. For each of four parameters of myocardial damage there was no statistically significant difference between control animals and those treated with prazosin, metoprolol, or verapamil. These data suggest that adrenergic or calcium channel-mediated mechanisms are not involved in the pathogenesis of postcountershock myocardial damage.

  14. Calcium influx through L-type channels attenuates skeletal muscle contraction via inhibition of adenylyl cyclases.

    Science.gov (United States)

    Menezes-Rodrigues, Francisco Sandro; Pires-Oliveira, Marcelo; Duarte, Thiago; Paredes-Gamero, Edgar Julian; Chiavegatti, Tiago; Godinho, Rosely Oliveira

    2013-11-15

    Skeletal muscle contraction is triggered by acetylcholine induced release of Ca(2+) from sarcoplasmic reticulum. Although this signaling pathway is independent of extracellular Ca(2+), L-type voltage-gated calcium channel (Cav) blockers have inotropic effects on frog skeletal muscles which occur by an unknown mechanism. Taking into account that skeletal muscle fiber expresses Ca(+2)-sensitive adenylyl cyclase (AC) isoforms and that cAMP is able to increase skeletal muscle contraction force, we investigated the role of Ca(2+) influx on mouse skeletal muscle contraction and the putative crosstalk between extracellular Ca(2+) and intracellular cAMP signaling pathways. The effects of Cav blockers (verapamil and nifedipine) and extracellular Ca(2+) chelator EGTA were evaluated on isometric contractility of mouse diaphragm muscle under direct electrical stimulus (supramaximal voltage, 2 ms, 0.1 Hz). Production of cAMP was evaluated by radiometric assay while Ca(2+) transients were assessed by confocal microscopy using L6 cells loaded with fluo-4/AM. Ca(2+) channel blockers verapamil and nifedipine had positive inotropic effect, which was mimicked by removal of extracellular Ca(+2) with EGTA or Ca(2+)-free Tyrode. While phosphodiesterase inhibitor IBMX potentiates verapamil positive inotropic effect, it was abolished by AC inhibitors SQ22536 and NYK80. Finally, the inotropic effect of verapamil was associated with increased intracellular cAMP content and mobilization of intracellular Ca(2+), indicating that positive inotropic effects of Ca(2+) blockers depend on cAMP formation. Together, our results show that extracellular Ca(2+) modulates skeletal muscle contraction, through inhibition of Ca(2+)-sensitive AC. The cross-talk between extracellular calcium and cAMP-dependent signaling pathways appears to regulate the extent of skeletal muscle contraction responses. © 2013 Published by Elsevier B.V.

  15. Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals.

    Science.gov (United States)

    Gupta, Ramesh K; Hussain, Talib; Panigrahi, G; Das, Avik; Singh, Gireesh Narayan; Sweety, K; Faiyazuddin, Md; Rao, Chandana Venkateswara

    2011-12-01

    To investigate the hepatoprotective potential of Solanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim. 50% ethanolic fruit extract of S. xanthocarpum (SXE, 100, 200 or 400 mg/kg body weight) was administered daily for 14 days in experimental animals. Liver injury was induced chemically, by CCl(4) administration (1 mL/kg i. p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Obtained results demonstrated that the treatment with SXE significantly (P<0.05-<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, SXE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that SXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. The results of this study strongly indicate the protective effect of SXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  16. Acute pulmonary injury induced by experimental muscle trauma Lesão pulmonar aguda induzida por trauma muscular experimental

    Directory of Open Access Journals (Sweden)

    Márcia Andréa da Silva Carvalho Sombra

    2011-01-01

    Full Text Available PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6: G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE (2 mg/kg body weight i.p.. Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p. rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung were collected for myeloperoxidase (MPO assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6: G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE (2 mg/kg peso corporal ip. Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97% de 100 ml/kg, i.p. por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão foram coletadas para avaliação da mieloperoxidase (MPO, e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutr

  17. Scintigraphic diagnosis of experimentally induced pericarditis in dogs using 99sup(m)Tc-labelled pyrophosphate

    International Nuclear Information System (INIS)

    Duska, F.; Novak, J.; Vizda, J.; Kubizek, J.; Simon, J.; Veverkova, O.; Karlova Universita, Hradec Kralove

    1981-01-01

    In the present paper the possibilities of scintigraphic diagnosis of experimental pericarditis are discussed. Pericarditis was induced by either talc or formaldehyde intrapericardially. In all animals the administration of talc as well as formaldehyde produced inflammatory changes which were more serious after formaldehyde. The scan of the talc pericarditis was carried out on the 7th day after operation and of the formaldehyde pericarditis on the 3rd, 7th and 14th day. No positive scintigraphic finding was made in any of the experimental animals, apart from a massive incorporation in the operation scars. The counting of radioactive impulses after the exstirpation of the tissue samples confirmed the scintigraphic findings. Statistical evaluation did not reveal any essential difference between the accumulation of the radiopharmaceutical into the pericarditis as well as into the pericardial bag in comparison with the control animals. Although our model does not exactly reflect the situation of patients suffering from pericarditis it may be assumed that pyrophosphate scintigraphy is not suitable for the diagnosis of acute pericarditis in clinical practice. (orig.) [de

  18. Experimental Study on the Effect of Calcitonin in Osteoporosis Induced by the Immobilization and Long-Term Glucocorticoid

    International Nuclear Information System (INIS)

    Park, Dong Jin; Lee, Sang Rae

    1989-01-01

    It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast has some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200 gm each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid and calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femoral head was markedly reduced than that of femoral shaft following ratio of cancellous and cortical components in both site. 2. glucocorticoid caused decrease in bone density of spine and femur, and there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in glucocorticoid and calcitonin injection simultaneously in later experimental period. 4. There was a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

  19. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study.

    Science.gov (United States)

    Lefaix, J L; Delanian, S; Leplat, J J; Tricaud, Y; Martin, M; Nimrod, A; Baillet, F; Daburon, F

    1996-05-01

    To establish how far liposomal copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD), respectively, reduce radiation-induced fibrosis (RIF), using a well-characterized pig model of RIF permitting the design of a controlled laboratory experiment. In this model of acute localized gamma irradiation simulating accidental overexposure in humans, three groups of five large white pigs were irradiated using a collimated 192Ir source to deliver a single dose of 160 Gy onto the skin surface (100%) of the outer side of the thigh. A well-defined block of subcutaneous fibrosis involving skin and skeletal muscle developed 6 months after irradiation. One experimental group of five pigs was then injected i.m. with 10 mg/10 kg b.wt. of Cu/Zn-SOD, twice a week for 3 weeks, and another experimental group of five was injected with 10 mg/10 kg b.wt. of Mn-SOD, three times a week for 3 weeks. Five irradiated control pigs were injected with physiological serum. Animals were assessed for changes in the density of the palpated fibrotic block and in the dimensions of the projected cutaneous surface. Block depth was determined by ultrasound. Physical and sonographic findings were confirmed by autopsy 12-14 weeks after completing SOD injections. The density, length, width, and depth of the fibrotic block, and the areas and volume of its projected cutaneous surface were compared before treatment, 1, 3, and 6 weeks thereafter, and at autopsy, 12-14 weeks after treatment ended. The experimental animals exhibited no change in behavior and no abnormal clinical or anatomic signs. Whether they were given Cu/Zn- or Mn-SOD, significant and roughly equivalent softening and shrinking of the fibrotic block were noted in all treated animals between the first week after treatment ended and autopsy, when mean regression was 45% for length and width, 30% for depth, and 70% for area and volume. Histologic examination showed completely normal muscle and subcutaneous tissue

  20. Vibration-induced particle formation during yogurt fermentation - Industrial vibration measurements and development of an experimental setup.

    Science.gov (United States)

    Körzendörfer, Adrian; Temme, Philipp; Nöbel, Stefan; Schlücker, Eberhard; Hinrichs, Jörg

    2016-07-01

    The aim of the study was to investigate the effects of vibrations during yogurt fermentation. Machinery such as pumps and switching valves generate vibrations that may disturb the gelation by inducing large particles. Oscillation measurements on an industrial yogurt production line showed that oscillations are transferred from pumps right up to the fermentation tanks. An experimental setup (20L) was developed to study the effect of vibrations systematically. The fermenters were decoupled with air springs to enable reference fermentations under idle conditions. A vibration exciter was used to stimulate the fermenters. Frequency sweeps (25-1005Hz, periodic time 10s) for 20min from pH5.4 induced large particles. The number of visible particles was significantly increased from 35±4 (reference) to 89±9 particles per 100g yogurt. Rheological parameters of the stirred yogurt samples were not influenced by vibrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Experimental study on flow-induced acoustic resonance in square closed side branch

    International Nuclear Information System (INIS)

    Zhang Hui; Gu Hanyang; Liu Xiaojing; Zhang Kai; Xie Yongcheng; Zu Hongbiao

    2014-01-01

    Flow-induced acoustic resonance is a phenomenon caused by the interaction of flow and acoustic fields in special structure. Acoustic resonance characteristic experiments were carried out on square closed side branch. The influences of the velocity in main pipe and the length of the side branch on acoustic resonance were studied. The range of occurrence and characteristics of pressure pulsation were analyzed. Three lengths of side branches (L/d=5.6 and 7) were experimentally studied and the Reynolds number in the experiment was 2.74 X 10 4 -2.429 X 10 5 while the Mach number was 0.025-0.218. The results show that the resonance frequency shows a lock-in phenomenon with the increase of velocity. As the length of the side branch increasing, the amplitude of the acoustic pressure and the resonance frequency decrease. In the considered structure, the acoustic resonance occurs when Strouhal number is 0.3-0.6 and 0.7-1.0. (authors)

  2. Experimental characterization of fire-induced response of rigid polyurethane foam

    Energy Technology Data Exchange (ETDEWEB)

    Chu, T.Y.; Gill, W.; Moore, J.W.; Hobbs, M.L.; Gritzo, L.A.; Moya, J.L.

    1995-12-31

    Reported is the result of an experimental investigation of fire-induced response of a 96 kg/m{sup 3} closed cell rigid polyurethane foam. The specimen is 0.37 m in diameter, and 152 mm thick, placed in a cylindrical test vessel. The fire condition is simulated by heating the bottom of the test vessel to 1283 K using a radiant heat source. Real-time x-ray shows that the degradation process involves the progression of a charring front into the virgin material. The charred region has a regular and graded structure consisting of a packed bubble outer layer and successive layers of thin shells. The layer-to-layer permeability appears to be poor. There are indications that gas vents laterally. The shell-like structure might be the result of lateral venting. Although the foam degradation process is quite complicated, the in-depth temperature responses in the uncharted foam appear to be consistent with steady state ablation. The measured temperature responses are well represented by the exponential distribution for steady state ablation. An estimate of the thermal diffusivity of the foam is obtained from the ablation model. The experiment is part of a more comprehensive program to develop material response models of foams and encapsulants.

  3. Role of the Use of Omental Flap in Prognosis of Cases with Induced Acute Pancreatitis in Experimental Dogs

    OpenAIRE

    Mohamed Hassan; Nader Shaaban; Ashraf M Abu-Seida; Mostafa Khodeir; Reem Jan; Hisham Elsharkawy; Engie Hefnawy

    2016-01-01

    Aim Acute pancreatitis frequently involves peripancreatic tissues and remote organ systems resulting in severe complications and high risk of mortality. Therefore, the present study was carried out to assess the effect of omental flap as a new treatment of acute pancreatitis. Methods Ten mongrel dogs with experimentally induced acute pancreatitis were randomly divided into two equal groups; treated and control groups. The pancreas was wrapped with omental flap in the treated group and the pan...

  4. Cellular and Ionic Mechanisms Underlying Effects of Cilostazol, Milrinone and Isoproterenol to Suppress Arrhythmogenesis in an Experimental Model of Early Repolarization Syndrome

    Science.gov (United States)

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-01-01

    Background Early Repolarization Syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and fibrillation (VF), leading to sudden cardiac death. Objective The present study tests the hypothesis that the Ito-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Methods Transmembrane action potentials (AP) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a transmural pseudo-ECG. The Ito-agonist NS5806 (7–15 μM) and ICa-blocker verapamil (2–3 uM) were used to induce an ER pattern and PVT. Results Following stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase-2-reentry (P2R) and PVT. Arrhythmic activity was suppressed in 7/8 preparations by cilostazol (10 μM), 6/7 by milrinone (2.5 μM) and 7/8 by isoproterenol (0.1–1μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Conclusions Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current in the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying development of P2R and VT/VF. PMID:26820510

  5. Experimental Induction of Genome Chaos.

    Science.gov (United States)

    Ye, Christine J; Liu, Guo; Heng, Henry H

    2018-01-01

    Genome chaos, or karyotype chaos, represents a powerful survival strategy for somatic cells under high levels of stress/selection. Since the genome context, not the gene content, encodes the genomic blueprint of the cell, stress-induced rapid and massive reorganization of genome topology functions as a very important mechanism for genome (karyotype) evolution. In recent years, the phenomenon of genome chaos has been confirmed by various sequencing efforts, and many different terms have been coined to describe different subtypes of the chaotic genome including "chromothripsis," "chromoplexy," and "structural mutations." To advance this exciting field, we need an effective experimental system to induce and characterize the karyotype reorganization process. In this chapter, an experimental protocol to induce chaotic genomes is described, following a brief discussion of the mechanism and implication of genome chaos in cancer evolution.

  6. Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

    Science.gov (United States)

    Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

    2003-11-01

    To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

  7. Experimental study of flow induced vibration of the planar fuel assembly

    International Nuclear Information System (INIS)

    Wang Jinhua; Bo Hanliang; Jiang Shengyao; Jia Haijun; Zheng Wenxiang; Min Gang; Qu Xinxing

    2005-01-01

    The paper studied the flow-induced vibration of the planar fuel assembly under scour of coolant through experiments, the study includes: the characteristics of the inherent vibration, the response to the flow-induced vibration in rating condition and the confirmation of the critical flow velocity's scope of the flow flexible instability. The velocity distributions in different flow channels formed by fuel plates in the assembly were measured, and the velocity distribution in the same flow channel was also measured. The experimental conclusions includes: the inherent vibration frequency of the planar fuel assembly is different for a little in each direction. The damp ratio corresponding to the assembly each rank's inherent frequency is small, and the damp ratio decreased with the increase of the corresponding inherent frequency. The velocity in different flow channels decreased from outside to inside, and the velocity in the middle channel was the least; the velocity in the same channel decreased from inside to outside, and the velocity in the middle position was the most. The vibration swing of the fuel assembly was small at rating condition, and the vibration swing of the fuel plates was larger than side plates. The vibration of the fuel assembly increased with the increase of the velocity, the vibration of the middle fuel plate were larger than the border fuel plate, and the vibration of the border fuel plate was larger than the side plate. The large scale vibration of the flow flexible instability didn't occur in the velocity scope of 0-18.8 m/s in the experiment, so the critical flow velocity of the flow flexible instability was not in the flow velocity scope of the experiment. (authors)

  8. Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade

    Directory of Open Access Journals (Sweden)

    Samra Bashir

    2011-01-01

    Full Text Available Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01–1 mg/mL relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K+-induced contractions (0.01–0.3 mg/mL, similar to verapamil, suggestive of calcium channel blockade (CCB. The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03–0.1 mg/mL rightward shift in the Ca++ concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100–300 mg/kg protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders.

  9. Pharmacological Evaluation of Prosopis cineraria (L. Druce in Gastrointestinal, Respiratory, and Vascular Disorders

    Directory of Open Access Journals (Sweden)

    Khalid Hussain Janbaz

    2012-01-01

    Full Text Available In this paper, a crude methanolic extract from the stem bark of Prosopis cineraria, a plant native of Pakistan, was tested for its possible presence of spasmolytic, bronchodilator, and vasodilator activities in an attempt to validate some of its folkloric uses. Moreover, attempts were made to provide plausible explanations of the observed biological activities. The extract caused relaxation of the spontaneous as well as K+ (80 mM-induced contractions at tissue bath concentrations of 3–10 mg/mL in isolated rabbit jejunum preparations, probably mediated through blockade of Ca+2 channels. This finding was further confirmed by the shifting of the Ca+2 concentration response curves to the rightward in a manner similar to verapamil used as a standard Ca+2 channel blocker. The extract also exhibited nonspecific relaxant effect on carbachol (1 μM- and K+ (80 mM-induced contractions in isolated rabbit tracheal preparations. The same effect was recorded for phenylephrine (11 μM and K+ (80 mM-induced contractions in isolated rabbit aortic preparations in a manner similar to verapamil. These observations confirm that observed bronchodilator and vasodilator activities were possibly mediated through blockade of Ca+2 channels. The above-mentioned observations validate the traditional use of the plant in the treatment of respiratory and gastrointestinal ailments.

  10. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  11. Proton-induced accelerated decay of the fungicide, vinclozolin, on TiO2 surface under solar irradiation: Experimental and DFT study.

    Science.gov (United States)

    Osipov, Ivan; Gorbachev, Mikhail Y; Gorinchoy, Natalia N

    2018-04-03

    The photochemical degradation of vinclozolin by addition of titanium dioxide on silica support has been examined both experimental and quantum-chemically. Solar irradiation of vinclozolin on silica with and without addition of titanium dioxide for 6 h resulted in 21% and 97.8% vinclozolin residues, respectively. In both these cases, phototransformation leads to the formation of (3,5-dichlorophenyl isocyanate) and (3,5-dichloroaniline). The presence of the intermediary product resulted from opening of the 2,4-oxazolidine-dione ring is also confirmed by GS-MS and LC-MS chromatography. The proton-induced mechanism of vinclozolin decay at the above experimental conditions is clarified on the base of DFT calculations.

  12. Bone Marrow-Derived Mononuclear Cell Therapy in Papain-Induced Experimental Pulmonary Emphysema

    Directory of Open Access Journals (Sweden)

    Mariana N. Machado

    2018-02-01

    Full Text Available Murine papain-induced emphysema is a model that reproduces many of the features found in patients. Bone marrow-derived mononuclear cells (BMMC have already been used to repair the alveolar epithelium in respiratory diseases, but not in the papain model. Thus, we hypothesized that BMMC could prevent the pathophysiological processes in papain-induced experimental emphysema. Female BALB/c mice received intratracheal instillation of 50 μL of saline (S groups or papain (P groups, 10 IU/50 μl of saline on days 1 and 7 of the experimental protocol. On the 14th day, 2 × 106 BMMC of male BALB/c mice (SC21 and PC21 or saline (SS21 and PS21 were injected by the jugular vein. Analyses were done on days 14 (S14 and P14 and 21 (SS21, PS21, SC21, and PC21 of the protocol. qPCR evaluated the presence of the Y chromosome in the lungs of BMMC recipient animals. Functional residual capacity (FRC, alveolar diameter, cellularity, elastic fiber content, concentrations of TNF-α, IL-1β, IL-6, MIP-2, KC, IFN-γ, apoptosis, mRNA expression of the dual oxidase (DUOX1 and DUOX2, production of H2O2 and DUOX activity were evaluated in lung tissue. We did not detect the Y chromosome in recipients' lungs. FRC, alveolar diameter, polymorphonuclear cells (PMN and levels of KC, MIP-2, and IFN-γ increased in P14 and PS21 groups; the changes in the latter were reverted by BMMC. TNF-α, IL-1β e IL-6 were similar in all groups. The amount of elastic fibers was smaller in P14 and PS21 than in other groups, and BMMC did not increase it in PC21 mice. PS21 animals showed increased DUOX activity and mRNA expression for DUOX1 and 2. Cell therapy reverted the activity of DUOX and mRNA expression of DUOX1. BMMC reduced mRNA expression of DUOX2. Apoptosis index was elevated in PS21 mice, which was reduced by cell therapy in PC21. Static compliance, viscoelastic component of elastance and pressure to overcome viscoelasticity were increased in P14 and PS21 groups. These changes and the

  13. Experimental cross sections for light-charged particle production induced by neutrons with energies between 25 and 65 MeV incident on aluminum

    International Nuclear Information System (INIS)

    Benck, S.; Slypen, I.; Meulders, J.P.; Corcalciuc, V.

    2001-01-01

    Experimental double-differential cross sections (d 2 σ/dΩdE) for fast neutron-induced proton, deuteron, triton, and alpha-particle production on aluminum are reported, at several incident neutron energies between 25 and 65 MeV, for outgoing particle energies above the experimental energy thresholds. Angular distributions were measured at laboratory angles between 20 deg. and 160 deg. . Reliable extrapolated spectra are derived for very forward (2.5 deg. and 10 deg. ) and very backward angles (170 deg. and 177.5 deg. ). Based on these experimental data, energy-differential (dσ/dE), angle-differential (dσ/dΩ), and total production cross sections (σ T ) are reported for each outgoing particle

  14. Dihydropyridines decrease X-ray-induced DNA base damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Wojewodzka, M., E-mail: marylaw@ichtj.waw.pl [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Gradzka, I.; Buraczewska, I.; Brzoska, K.; Sochanowicz, B. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Goncharova, R.; Kuzhir, T. [Institute of Genetics and Cytology, Belarussian National Academy of Sciences, Minsk (Belarus); Szumiel, I. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland)

    2009-12-01

    Compounds with the structural motif of 1,4-dihydropyridine display a broad spectrum of biological activities, often defined as bioprotective. Among them are L-type calcium channel blockers, however, also derivatives which do not block calcium channels exert various effects at the cellular and organismal levels. We examined the effect of sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate (denoted here as DHP and previously also as AV-153) on X-ray-induced DNA damage and mutation frequency at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in Chinese hamster ovary CHO-K1 cells. Using formamido-pyrimidine glycosylase (FPG) comet assay, we found that 1-h DHP (10 nM) treatment before X-irradiation considerably reduced the initial level of FPG-recognized DNA base damage, which was consistent with decreased 8-oxo-7,8-dihydro-2'-deoxyguanosine content and mutation frequency lowered by about 40%. No effect on single strand break rejoining or on cell survival was observed. Similar base damage-protective effect was observed for two calcium channel blockers: nifedipine (structurally similar to DHP) or verapamil (structurally unrelated). So far, the specificity of the DHP-caused reduction in DNA damage - practically limited to base damage - has no satisfactory explanation.

  15. Protective effects of total glucosides of paeony and the underlying mechanisms in carbon tetrachloride-induced experimental liver injury

    Science.gov (United States)

    Qin, Ying; Tian, Ya-ping

    2011-01-01

    Introduction We explored the protective effects of total glucosides of paeony (TGP) and the underlying mechanisms in carbon tetrachloride (CCl4)-induced experimental liver injury in mice. Material and methods Chronic liver damage was induced by intraperitoneal injection of CCl4 (0.5 µl/g) three times per week for 8 weeks. Mice also received 25, 50 or 100 mg/kg TGP. Liver sections were stained with haematoxylin/eosin. Serum amino transferases, lipid peroxidation and tumour necrosis factor-α (TNF-α) levels were determined using commercial assays. Quantitative real-time polymerase chain reaction was used to determine the changes in hepatic TNF-α, COX-2, iNOS and HO-1 expression. Protein levels of nitric oxide synthase, cyclooxygenase-2, haem oxygenase-1 and cytochrome P450 2E1 were determined by western blotting. Results Histological results showed that TGP improved the CCl4-induced changes in liver structure and alleviated lobular necrosis. The increases in serum protein and hepatic mRNA expression of TNF-α induced by CCl4 treatment were suppressed by TGP. Total glucosides of paeony also attenuated the increase the expression in iNOS and CYP2E1 but augmented the increase in HO-1.The mRNA and protein expression levels of inducible HO-1 increased significantly after CCl4 treatment. Conclusions Total glucosides of paeony protects hepatocytes from oxidative damage induced by CCl4. Total glucosides of paeony may achieve these effects by enhancing HO-1 expression and inhibiting the expression of proinflammatory mediators. PMID:22291795

  16. Kaempferol-human serum albumin interaction: Characterization of the induced chirality upon binding by experimental circular dichroism and TDDFT calculations

    Science.gov (United States)

    Matei, Iulia; Ionescu, Sorana; Hillebrand, Mihaela

    2012-10-01

    The experimental induced circular dichroism (ICD) and absorption spectra of the achiral flavonoid kaempferol upon binding to human serum albumin (HSA) were correlated to electronic CD and UV-vis spectra theoretically predicted by time-dependent density functional theory (TDDFT). The neutral and four anionic species of kaempferol in various conformations were considered in the calculations. The appearance of the experimental ICD signal was rationalized in terms of kaempferol binding to HSA in a distorted, chiral, rigid conformation. The comparison between the experimental and simulated spectra allowed for the identification of the kaempferol species that binds to HSA, namely the anion generated by deprotonation of the hydroxyl group in position 7. This approach constitutes a convenient method for evidencing the binding species and for determining its conformation in the binding pocket of the protein. Its main advantage over the UV-vis absorption method lays in the fact that only the bound ligand species gives an ICD signal.

  17. Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome.

    Science.gov (United States)

    Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles

    2016-06-01

    Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  18. Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

    Energy Technology Data Exchange (ETDEWEB)

    Guilloteau, L.; Pepin, M.; Pardon, P.; Le Pape, A. (Institut National de la Recherche Agronomique, Nouzilly (France))

    1990-10-01

    The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteria into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.

  19. Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

    International Nuclear Information System (INIS)

    Guilloteau, L.; Pepin, M.; Pardon, P.; Le Pape, A.

    1990-01-01

    The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteria into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process

  20. Integral analyses of fission product retention at mitigated thermally-induced SGTR using ARTIST experimental data

    International Nuclear Information System (INIS)

    Rýdl, Adolf; Lind, Terttaliisa; Birchley, Jonathan

    2016-01-01

    Highlights: • Source term analyses in a PWR of mitigated thermally-induced SGTR scenario performed. • Experimental ARTIST program results on aerosol scrubbing efficiency used in analyses. • Results demonstrate enhanced aerosol retention in a flooded steam generator. • High aerosol retention cannot be predicted by current theoretical scrubbing models. - Abstract: Integral source-term analyses are performed using MELCOR for a PWR Station Blackout (SBO) sequence leading to induced steam generator tube rupture (SGTR). In the absence of any mitigation measures, such a sequence can result in a containment bypass where the radioactive materials can be released directly to the environment. In some SGTR scenarios flooding of the faulted SG secondary side with water can mitigate the accident escalation and also the release of aerosol-borne and volatile radioactive materials. Data on the efficiency of aerosol scrubbing in an SG tube bundle were obtained in the international ARTIST project. In this paper ARTIST data are used directly with parametric MELCOR analyses of a mitigated SGTR sequence to provide more realistic estimates of the releases to environment in such a type of scenario or similar. Comparison is made with predictions using the default scrubbing model in MELCOR, as a representative of the aerosol scrubbing models in current integral codes. Specifically, simulations are performed for an unmitigated sequence and 2 cases where the SG secondary was refilled at different times after the tube rupture. The results, reflecting the experimental observations from ARTIST, demonstrate enhanced aerosol retention in the highly turbulent two-phase flow conditions caused by the complex geometry of the SG secondary side. This effect is not captured by any of the models currently available. The underlying physics remains only partly understood, indicating need for further studies to support a more mechanistic treatment of the retention process.

  1. Interleukin-12 promotes activation of effector cells that induce a severe destructive granulomatous form of murine experimental autoimmune thyroiditis.

    OpenAIRE

    Braley-Mullen, H.; Sharp, G. C.; Tang, H.; Chen, K.; Kyriakos, M.; Bickel, J. T.

    1998-01-01

    Granulomatous inflammatory lesions are a major histopathological feature of a wide spectrum of human infectious and autoimmune diseases. Experimental autoimmune thyroiditis (EAT) with granulomatous histopathological features can be induced by mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg and anti-interleukin-2 receptor (anti-IL-2R), anti-IL-2, or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibody (MAb). These studies suggested that IFN-gamma-producing T...

  2. An experimental approach to improve the Monte Carlo modelling of offline PET/CT-imaging of positron emitters induced by scanned proton beams

    International Nuclear Information System (INIS)

    Bauer, J; Unholtz, D; Kurz, C; Parodi, K

    2013-01-01

    We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β + activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β + activity induced in the investigated

  3. An experimental approach to improve the Monte Carlo modelling of offline PET/CT-imaging of positron emitters induced by scanned proton beams

    Science.gov (United States)

    Bauer, J.; Unholtz, D.; Kurz, C.; Parodi, K.

    2013-08-01

    We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β+ activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β+ activity induced in the investigated

  4. Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

    Science.gov (United States)

    Cannon, C M; Pozniak, J; Scott, M C; Ito, D; Gorden, B H; Graef, A J; Modiano, J F

    2015-03-01

    We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted. © 2013 Blackwell Publishing Ltd.

  5. Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit.

    Directory of Open Access Journals (Sweden)

    Oscar Julián Arias-Mutis

    Full Text Available Metabolic syndrome (MetS has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15 or MetS group (n = 16, fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05. Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular

  6. Experimental pleurodesis induced by antibiotics (macrolides or quinolones Pleurodese experimental induzida por antibióticos (macrolídeos e quinolonas

    Directory of Open Access Journals (Sweden)

    Lisete R. Teixeira

    2006-01-01

    Full Text Available PURPOSE: Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin or quinolones (levofloxacin and gatifloxacin in inducing experimental pleurodesis in rabbits. METHOD: Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. RESULTS: The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. CONCLUSION: The macrolides (azithromycin or clarithromycin and the quinolones (levofloxacin or gatifloxacin when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.OBJETIVO: A pleurodese química representa uma ferramenta terapêutica utilizada no tratamento dos processos pleurais recidivantes, principalmente nos derrames neoplásicos. A escolha do melhor esclerosante pleural é ainda motivo de controvérsia, não havendo consenso com relação ao agente considerado ideal. O objetivo deste estudo é avaliar a efetividade dos macrolídeos (azitromicina e claritromicina e das quinolonas (levofloxacina e gatifloxacina na indução de pleurodese experimental em coelhos. MÉTODOS: Quarenta animais randomizados em grupos de 10, receberam, em volume total de 2 mL, estas drogas através de injeção intrapleural. RESULTADOS: Após 28 dias, os animais foram sacrificados sendo avaliada a cavidade pleural. A

  7. Experimental study of acoustic damping induced by gas-liquid scheme injectors in a combustion chamber

    International Nuclear Information System (INIS)

    Kim, Hak Soon; Sohn, Chae Hoon

    2007-01-01

    In a liquid rocket engine, acoustic damping induced by gas-liquid scheme injectors is studied experimentally for combustion stability by adopting linear acoustic test. In the previous work, it has been found that gas-liquid scheme injector can play a significant role in acoustic damping or absorption when it is tuned finely. Based on this finding, acoustic-damping characteristics of multi-injectors are intensively investigated. From the experimental data, it is found that acoustic oscillations are almost damped out by multi-injectors when they have the tuning length proposed in the previous study. The length corresponds to a half wavelength of the first longitudinal overtone mode traveling inside the injector with the acoustic frequency intended for damping in the chamber. But, new injector-coupled acoustic modes show up in the chamber with the injectors of the tuning length although the target mode is nearly damped out. And, appreciable frequency shift is always observed except for the case of the worst tuned injector. Accordingly, it is proposed that the tuning length is adjusted to have the shorter length than a half wavelength when these phenomena are considered

  8. The bystander effect in experimental systems and compatibility with radon-induced lung cancer in humans

    International Nuclear Information System (INIS)

    Little, M.P.; Wakeford, R.

    2002-01-01

    Bystander effects following exposure to α-particles have been observed in C3H 10T 1/2 cells and in other experimental systems, and imply that linearly extrapolating low-dose risks from high-dose data might materially underestimate risk. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4-4.0, with an upper 95% confidence limit (CL) of about 14. Assuming that the bystander effect observed in the C3H 10T 1/2 data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% CL of about 7. As a consequence, the bystander effect observed in the C3H 10T 1/2 system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α-particle exposure are surveyed; some of these data are more compatible with the epidemiological data. (author)

  9. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    Science.gov (United States)

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  10. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

    2003-01-01

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  11. Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes

    Directory of Open Access Journals (Sweden)

    Trine Krogh-Madsen

    2017-12-01

    Full Text Available In silico cardiac myocyte models present powerful tools for drug safety testing and for predicting phenotypical consequences of ion channel mutations, but their accuracy is sometimes limited. For example, several models describing human ventricular electrophysiology perform poorly when simulating effects of long QT mutations. Model optimization represents one way of obtaining models with stronger predictive power. Using a recent human ventricular myocyte model, we demonstrate that model optimization to clinical long QT data, in conjunction with physiologically-based bounds on intracellular calcium and sodium concentrations, better constrains model parameters. To determine if the model optimized to congenital long QT data better predicts risk of drug-induced long QT arrhythmogenesis, in particular Torsades de Pointes risk, we tested the optimized model against a database of known arrhythmogenic and non-arrhythmogenic ion channel blockers. When doing so, the optimized model provided an improved risk assessment. In particular, we demonstrate an elimination of false-positive outcomes generated by the baseline model, in which simulations of non-torsadogenic drugs, in particular verapamil, predict action potential prolongation. Our results underscore the importance of currents beyond those directly impacted by a drug block in determining torsadogenic risk. Our study also highlights the need for rich data in cardiac myocyte model optimization and substantiates such optimization as a method to generate models with higher accuracy of predictions of drug-induced cardiotoxicity.

  12. Effect of Camel Milk on Oxidative Stresses in Experimentally Induced Diabetic Rabbits

    Directory of Open Access Journals (Sweden)

    Esraa Tantawy

    2010-06-01

    Full Text Available Camel milk has an importance in the treatment of diabetes. It has been shown that the patients who drink camel milk daily, their need to insulin decrease. Therefore, this study aimed to investigate the effect of camel milk in comparison with insulin treatment in experimentally-induced diabetes. This study was carried out on forty male New Zealand rabbits, divided into four groups with ten rabbits in each. The first group G1 was considered as control non-diabetic group and received only normal saline solution. The other animals were injected intravenously with alloxan for induction of diabetes mellitus and then divided into three groups' ten rabbits each as the follows: G2 considered as control diabetic and left untreated, G3 was considered as diabetic and treated with insulin, and G4 was considered as diabetic and received camel milk. At the end of the experiment (4 weeks, blood (whole blood & serum and tissue samples (liver, kidney and pancreas were collected from all the animals for analysis of: enzymatic SOD and catalase, non-enzymatic GSH antioxidant enzyme activities. Serum malondialdeyde, glucose, insulin and lipid profile also were analyzed. The results showed that the camel milk was effective in the treatment of diabetes in comparison to insulin treatment alone. In addition to its hypoglycemic effect, camel milk improved the diabetes-induced oxidative stress. The histopathological evaluations demonstrated that there was a regeneration in β cells and the islets of Langerhans among the pancreatic acini in rabbits receiving camel milk. Our findings suggested that the camel milk administration in case of insulin dependant diabetes mellitus might be recommended as an oral anti-diabetic remedy.

  13. Experimental Evidence of Momentum Transport Induced by an Up-Down Asymmetric Magnetic Equilibrium in Toroidal Plasmas

    International Nuclear Information System (INIS)

    Camenen, Y.; Peeters, A. G.; Casson, F. J.; Hornsby, W. A.; Snodin, A. P.; Szepesi, G.; Bortolon, A.; Duval, B. P.; Federspiel, L.; Karpushov, A. N.; Piras, F.; Sauter, O.

    2010-01-01

    The first experimental evidence of parallel momentum transport generated by the up-down asymmetry of a toroidal plasma is reported. The experiments, conducted in the Tokamak a Configuration Variable, were motivated by the recent theoretical discovery of ion-scale turbulent momentum transport induced by an up-down asymmetry in the magnetic equilibrium. The toroidal rotation gradient is observed to depend on the asymmetry in the outer part of the plasma leading to a variation of the central rotation by a factor of 1.5-2. The direction of the effect and its magnitude are in agreement with theoretical predictions for the eight possible combinations of plasma asymmetry, current, and magnetic field.

  14. Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs

    Directory of Open Access Journals (Sweden)

    Kieran eAlden

    2012-07-01

    Full Text Available The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signalling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex 3-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically the role of different tissue inducer cell populations in the dynamic formation of Peyer's Patches has been examined. Utilising approaches from critical systems engineering an unbiased model of lymphoid tissue inducer cell function has been developed, that permits the development of emerging behaviours that are statistically not different from that observed in vivo. These results provide the confidence to utilise statistical methods to explore how the simulator predicts cellular behaviour and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine begins to have an influence on observed behaviour, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilising experimental approaches.

  15. Radiographic evaluation of experimentally induced nephrosis in goats

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R.; Pandey, N. N.; Singh, G. R.; Setia, H. C. [Indian Veterinary Research Institute, Izatnagar (India)

    1995-06-15

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants.

  16. Radiographic evaluation of experimentally induced nephrosis in goats

    International Nuclear Information System (INIS)

    Kumar, R.; Pandey, N.N.; Singh, G.R.; Setia, H.C.

    1995-01-01

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants

  17. Numerical and experimental investigation of laser induced plasma spectrum of aluminum in the presence of a noble gas

    International Nuclear Information System (INIS)

    Rezaei, Fatemeh; Tavassoli, Seyed Hassan

    2012-01-01

    Laser-induced plasma emission of an aluminum target in helium gas at 1 atm pressure is numerically and experimentally investigated. A laser pulse at wavelength of 266 nm and pulse duration of 10 ns has been considered. Laser ablation is calculated by a one dimensional model based on thermal evaporation mechanism. Spatial and temporal parameters of plasma expansion are determined by using hydrodynamic equations. Three kinds of plasma emission, including Bremsstrahlung, recombination and spectral emissions are considered for modeling the spectrum. Strong lines of aluminum and helium in wavelength interval of 200 to 450 nm are selected. Aluminum spectrum in UV range is depicted and compared with other spectral ranges. Temporal and spatial evolution of plasma emission up to 200 ns after the laser irradiation is studied. The effect of laser energy on the plasma spectrum is studied. An experimental set-up is arranged to compare numerical calculations with experimental results. Experimental and numerical results illustrate that helium line widths and peak intensities become narrower and weaker with time, respectively. Spatial distribution of spectrum shows that for closer distance to the sample surface, an intense continuous emission is observed, while at the farther distance, continuous emission decreases and spectral lines become sharper. A good coincidence is observed between experimental and numerical results. - Highlights: ► Aluminum plasma emission in helium is numerically and experimentally studied. ► Spectral, Bremsstrahlung and recombination emissions in spectrum are calculated. ► All strong lines of aluminum and helium are chosen for spectrum simulation. ► Line widths and peak intensities at later times become narrower and weaker. ► At specific optimum position, the maximum of signal peaks is acquired.

  18. Assessment of contrast-enhanced ultrasonography of the hepatic vein for detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs.

    Science.gov (United States)

    Morishita, Keitaro; Hiramoto, Akira; Michishita, Asuka; Takagi, Satoshi; Hoshino, Yuki; Itami, Takaharu; Lim, Sue Yee; Osuga, Tatsuyuki; Nakamura, Sayuri; Ochiai, Kenji; Nakamura, Kensuke; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

    2017-04-01

    OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.

  19. Experimental Study on Piezoelectric Energy Harvesting from Vortex-Induced Vibrations and Wake-Induced Vibrations

    Directory of Open Access Journals (Sweden)

    Min Zhang

    2016-01-01

    Full Text Available A rigid circular cylinder with two piezoelectric beams attached on has been tested through vortex-induced vibrations (VIV and wake-induced vibrations (WIV by installing a big cylinder fixed upstream, in order to study the influence of the different flow-induced vibrations (FIV types. The VIV test shows that the output voltage increases with the increases of load resistance; an optimal load resistance exists for the maximum output power. The WIV test shows that the vibration of the small cylinder is controlled by the vortex frequency of the large one. There is an optimal gap of the cylinders that can obtain the maximum output voltage and power. For a same energy harvesting device, WIV has higher power generation capacity; then the piezoelectric output characteristics can be effectively improved.

  20. Experimental headache in humans

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    1995-01-01

    The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose......-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache....... N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological...

  1. Experimental study and nuclear model calculations of {sup 3}He-induced nuclear reactions on zinc

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abyad, M.; Mohamed, Gehan Y. [Nuclear Research Centre, Atomic Energy Authority, Physics Department (Cyclotron Facility), Cairo (Egypt); Ditroi, F.; Takacs, S.; Tarkanyi, F. [Hungarian Academy of Sciences (ATOMKI), Institute for Nuclear Research, Debrecen (Hungary)

    2017-05-15

    Excitation functions of {sup 3}He-induced nuclear reactions on natural zinc were measured using the standard stacked-foil technique and high-resolution gamma-ray spectrometry. From their threshold energies up to 27 MeV, the cross-sections for {sup nat}Zn ({sup 3}He,xn) {sup 69}Ge, {sup nat}Zn({sup 3}He,xnp) {sup 66,67,68}Ga, and {sup nat}Zn({sup 3}He,x){sup 62,65}Zn reactions were measured. The nuclear model codes TALYS-1.6, EMPIRE-3.2 and ALICE-IPPE were used to describe the formation of these products. The present data were compared with the theoretical results and with the available experimental data. Integral yields for some important radioisotopes were determined. (orig.)

  2. Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

    Science.gov (United States)

    Das, Jharana; Singh, Rameshwar; Sharma, Deepak

    2017-05-01

    Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na + ,K + -ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na + ,K + -ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

  3. Deeply inelastic transfer reactions induced by heavy ions in rare earth targets. II. Interpretation of experimental data

    International Nuclear Information System (INIS)

    Rivet, M.F.; Bimbot, R.; Ngo, C.

    1979-01-01

    The experimental angular distributions and cross sections for a series of deeply inelastic transfer reactions induced by various projectiles in rare earth targets have been interpreted using a model which includes a dynamical coupling between relative motion and mass asymmetry and treats statistical fluctuations. As the transfer reactions considered correspond to an increase of the potential energy of the composite system their observation is mainly due to fluctuations. The calculation reproduces correctly the angular distributions, but the cross sections are underestimated. Several effects are discussed which may increase these cross sections and are neglected in the calculation

  4. Experimental radiation carcinogenesis is studies at NIRS

    International Nuclear Information System (INIS)

    Sado, Toshihiko

    1992-01-01

    Experimental radiation carcinogenesis studies conducted during the past decade at NIRS are briefly reviewed. They include the following: 1) Age dependency of susceptibility to radiation carcinogenesis. 2) Radiation-induced myeloid leukemia. 3) Mechanism of fractionated X-irradiation (FX) induced thymic lymphomas. 4) Significance of radiation-induced immunosuppression in radiation carcinogenesis in vivo. 5) Other ongoing studies. (author)

  5. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  6. Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

    Directory of Open Access Journals (Sweden)

    Waleska C. Dornas

    2010-08-01

    Full Text Available Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

  7. Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

    Science.gov (United States)

    Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

    2008-12-01

    To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

  8. Experimental and analytical studies on pedestrian induced footbridge vibrations

    DEFF Research Database (Denmark)

    Gudmundsson, Gudmundur Valur; Ingólfsson, Einar Thór; Einarsson, Baldvin

    2007-01-01

    characteristics and to measure the response of the bridges to human induced excitation such as walking, running and jumping. Two of the bridges were a part of a design competition related to the realignment of an existing highway in the city centre of Reykjavik in 2005. The bridges have similar cross sections...... modes corresponding to the measured values. The models were subsequently used to calculate the predicted acceleration according to the preliminary version of the Eurocode (ENV 1992-2: Concrete bridges) using time-history analysis with a moving load as representative for a single pedestrian. The load...... models describing human-induced vibrations on structures in current literature and standards are explained, both for a single person walking or running and crowd loading. The measured vertical acceleration induced by single pedestrians was compared against the predictions and it was found that all...

  9. Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

    Science.gov (United States)

    Fernández-Espejo, Emilio; Bis-Humbert, Cristian

    2018-06-06

    3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

  10. Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

    Directory of Open Access Journals (Sweden)

    Rafael Fenutría

    Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

  11. Determination of ultra-short laser induced damage threshold of KH2PO4 crystal: Numerical calculation and experimental verification

    Directory of Open Access Journals (Sweden)

    Jian Cheng

    2016-03-01

    Full Text Available Rapid growth and ultra-precision machining of large-size KDP (KH2PO4 crystals with high laser damage resistance are tough challenges in the development of large laser systems. It is of high interest and practical significance to have theoretical models for scientists and manufacturers to determine the laser-induced damage threshold (LIDT of actually prepared KDP optics. Here, we numerically and experimentally investigate the laser-induced damage on KDP crystals in ultra-short pulse laser regime. On basis of the rate equation for free electron generation, a model dedicated to predicting the LIDT is developed by considering the synergistic effect of photoionization, impact ionization and decay of electrons. Laser damage tests are performed to measure the single-pulse LIDT with several testing protocols. The testing results combined with previously reported experimental data agree well with those calculated by the model. By taking the light intensification into consideration, the model is successfully applied to quantitatively evaluate the effect of surface flaws inevitably introduced in the preparation processes on the laser damage resistance of KDP crystals. This work can not only contribute to further understanding of the laser damage mechanisms of optical materials, but also provide available models for evaluating the laser damage resistance of exquisitely prepared optical components used in high power laser systems.

  12. Potassium-induced contraction in the lamb proximal urethra: Involvement of norepinephrine and different calcium entry pathways

    International Nuclear Information System (INIS)

    Garcia-Pascual, A.; Costa, G.; Isla, M.; Jimenez, E.; Garcia-Sacristan, A.

    1991-01-01

    The purpose of this work was to investigate the mechanisms involved in the peculiar biphasic response of the lamb urethral smooth muscle to high K+ solutions. The relative amplitude of the phasic and tonic components of the contraction and its reproducibility were dependent on the concentration of K+ used. Only concentrations higher than 80 mM (i.e., 120 mM) showed a tonic component greater in amplitude than the phasic one and manifested a tachyphylactic effect. Phentolamine (10(-6) M), prazosin (10(-6) M) and chemical denervation with 6-hydroxydopamine significantly inhibited the tonic component of the K+ (120 mM)-induced contraction, modifying its morphology. Reproducible contractions to K+ (120 mM) could be obtained in the presence of prazosin (10(-6) M) or cocaine (10(-6) M). The preparations were also shown to accumulate [3H]noradrenaline and release it upon depolarization with K+ (60 and 120 mM). Calcium removal inhibited the K+ (120 mM)-induced contraction. After addition of calcium (0.5-5 mM) the contractile activity was restored. Nifedipine (10(-6) M) and verapamil (10(-6) M) but not sodium nitroprusside (10(-6) M) significantly blocked the contractile response for calcium as well as the phasic component of the K+ contraction in calcium-containing medium. In preparations treated with prazosin (10(-6) M) the tonic component of the K+ (120 mM) contraction was more sensitive to nifedipine and removal of extracellular calcium than the phasic one

  13. Experimental study of boundary layer transition on an airfoil induced by periodically passing wake (II)

    Energy Technology Data Exchange (ETDEWEB)

    Park, T.C. [Seoul National University Graduate School, Seoul (Korea); Jeon, W.P.; Kang, S.H. [Seoul National University, Seoul (Korea)

    2001-06-01

    This paper describes the phenomena of wake-induced transition of the boundary layers on a NACA0012 airfoil using measured phase-averaged data. Especially, the phase-averaged wall shear stresses are reasonably evaluated using the principle of Computational Preston Tube Method. Due to the passing wake, the turbulent patch is generated in the laminar boundary layer on the airfoil and the boundary layer becomes temporarily transitional. The patches propagate downstream with less speed than free-stream velocity and merge with each other at further downstream station, and the boundary layer becomes more transitional. The generation of turbulent patch at the leading edge of the airfoil mainly depends on velocity defects and turbulent intensity profiles of passing wakes. However, the growth and merging of turbulent patches depend on local streamwise pressure gradients as well as characteristics of turbulent patches. In this transition process, the present experimental data show very similar features to the previous numerical and experimental studies. It is confirmed that the two phase-averaged mean velocity dips appear in the outer region of transitional boundary layer for each passing cycle. Relatively high values of the phase-averaged turbulent fluctuations in the outer region indicate the possibility that breakdown occurs in the outer layer not near the wall. (author). 21 refs., 12 figs.

  14. Numerical and experimental investigation of laser induced plasma spectrum of aluminum in the presence of a noble gas

    Energy Technology Data Exchange (ETDEWEB)

    Rezaei, Fatemeh, E-mail: f_rezaei@sbu.ac.ir; Tavassoli, Seyed Hassan

    2012-12-01

    Laser-induced plasma emission of an aluminum target in helium gas at 1 atm pressure is numerically and experimentally investigated. A laser pulse at wavelength of 266 nm and pulse duration of 10 ns has been considered. Laser ablation is calculated by a one dimensional model based on thermal evaporation mechanism. Spatial and temporal parameters of plasma expansion are determined by using hydrodynamic equations. Three kinds of plasma emission, including Bremsstrahlung, recombination and spectral emissions are considered for modeling the spectrum. Strong lines of aluminum and helium in wavelength interval of 200 to 450 nm are selected. Aluminum spectrum in UV range is depicted and compared with other spectral ranges. Temporal and spatial evolution of plasma emission up to 200 ns after the laser irradiation is studied. The effect of laser energy on the plasma spectrum is studied. An experimental set-up is arranged to compare numerical calculations with experimental results. Experimental and numerical results illustrate that helium line widths and peak intensities become narrower and weaker with time, respectively. Spatial distribution of spectrum shows that for closer distance to the sample surface, an intense continuous emission is observed, while at the farther distance, continuous emission decreases and spectral lines become sharper. A good coincidence is observed between experimental and numerical results. - Highlights: Black-Right-Pointing-Pointer Aluminum plasma emission in helium is numerically and experimentally studied. Black-Right-Pointing-Pointer Spectral, Bremsstrahlung and recombination emissions in spectrum are calculated. Black-Right-Pointing-Pointer All strong lines of aluminum and helium are chosen for spectrum simulation. Black-Right-Pointing-Pointer Line widths and peak intensities at later times become narrower and weaker. Black-Right-Pointing-Pointer At specific optimum position, the maximum of signal peaks is acquired.

  15. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

    Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

  16. PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.

    Science.gov (United States)

    Bergenholm, Linnéa; Collins, Teresa; Evans, Neil D; Chappell, Michael J; Parkinson, Joanna

    2016-01-01

    Pharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. This investigation aims to develop and evaluate PKPD models for describing QRS and PR effects in routine safety studies. Exposure and telemetry data from safety pharmacology studies in conscious beagle dogs were acquired. Mixed effects baseline and PK-QRS/PR models were developed for the anti-arrhythmic compounds AZD1305, flecainide, quinidine and verapamil and the anti-muscarinic compounds AZD8683 and AZD9164. RR interval correction and circadian rhythms were investigated for predicting baseline variability. Individual PK predictions were used to drive the pharmacological effects evaluating linear and non-linear direct and effect compartment models. Conduction slowing induced by the tested anti-arrhythmics was direct and proportional at low exposures, whilst time delays and non-linear effects were evident for the tested anti-muscarinics. AZD1305, flecainide and quinidine induced QRS widening with 4.2, 10 and 5.6% μM(-1) unbound drug. AZD1305 and flecainide also prolonged PR with 13.5 and 11.5% μM(-1). PR prolongations induced by the anti-muscarinics and verapamil were best described by Emax models with maximal effects ranging from 55 to 95%. RR interval correction and circadian rhythm improved PR but not QRS modelling. However, circadian rhythm had minor impact on estimated drug effects. Baseline and drug-induced effects on QRS and PR intervals can be effectively described with PKPD models using routine data, providing quantitative safety information to support drug discovery and development. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Antidiarrheal and Antispasmodic Activities of Buddleja polystachya are Mediated Through Dual Inhibition of Ca(++) Influx and Phosphodiesterase Enzyme.

    Science.gov (United States)

    Rehman, Najeeb-ur; Gilani, Anwarul-Hassan; Khan, Aslam; Nazneen, Maryam; El Gamal, Ali A; Fawzy, Ghada A; Al-Ati, Hanan Y; Abdel-kader, Maged S

    2015-08-01

    This study describes the antidiarrheal and antispasmodic activities of the hydro-alcoholic extract of Buddleja polystachya (Bp.Cr) with possible mode of action explored along with activity-directed fractionation. Bp.Cr and its aqueous (Bp.Aq) and organic fractions, petroleum ether (Bp.Pet), dichloromethane (Bp.DCM), ethylacetate (Bp.EtAc) and butanol (Bp.But), were tested using the in-vivo and in-vitro assays. The crude extract (100-300 mg/kg) showed 20 and 60% protection of castor oil-induced diarrhea in mice. In isolated rabbit jejunum, Bp.Cr like papaverine inhibited spontaneous and high K(+) (80 mM)-induced contractions equi-potently. In guinea-pig ileum, Bp.Cr showed a moderate spasmogenic effect. The activity-directed fractionation revealed that the spasmolytic activity was concentrated in the organic fractions and spasmogenic component in the aqueous fraction. Amongst the organic fractions, BP.DCM and Bp.Pet inhibited spontaneous and high K(+) -induced contractions equi-potently, while Bp.But, like verapamil was more potent against high K(+) . The crude extract and its organic fractions caused rightward shift in the Ca(++) -concentration response curves (CRCs), similar to verapamil, and all except Bp.But potentiated the isoprenaline-inhibitory CRCs to the left, similar to papaverine. The results of this study indicate that the crude extract of B. polystachya possesses antidiarrheal and antispasmodic activities, mediated possibly through dual inhibition of Ca(++) influx and phospodiesterase enzyme. Copyright © 2015 John Wiley & Sons, Ltd.

  18. A new calculation method adapted to the experimental conditions for determining samples γ-activities induced by 14 MeV neutrons

    International Nuclear Information System (INIS)

    Rzama, A.; Erramli, H.; Misdaq, M.A.

    1994-01-01

    Induced gamma-activities of different disk shaped irradiated samples and standards with 14 MeV neutrons have been determined by using a Monte Carlo calculation method adapted to the experimental conditions. The self-absorption of the multienergetic emitted gamma rays has been taken into account in the final samples activities. The influence of the different activation parameters has been studied. Na, K, Cl and P contents in biological (red beet) samples have been determined. ((orig.))

  19. Repair of experimental plaque-induced periodontal disease in dogs.

    Science.gov (United States)

    Shoukry, M; Ben Ali, L; Abdel Naby, M; Soliman, A

    2007-09-01

    Forty mongrel dogs were used in this study for induction of periodontal disease by placing subgingival silk ligatures affecting maxillary and mandibular premolar teeth during a 12-month period. Experimental premolar teeth received monthly clinical, radiographic, and histometric/pathologic assessments. The results demonstrated significant increases in scores and values of periodontal disease parameters associated with variable degrees of alveolar bone loss. The experimental maxillary premolar teeth exhibited more severe and rapid rates of periodontal disease compared with mandibular premolar teeth. Histometric analysis showed significant reduction in free and attached gingiva of the experimental teeth. Histopathological examination of buccolingual sections from experimental premolar teeth showed the presence of rete pegs within the sulcular epithelium with acanthosis and erosive changes, widening of the periodontal ligament, and alveolar bone resorption. Various methods for periodontal repair were studied in 194 experimental premolar teeth exhibiting different degrees of periodontal disease. The treatment plan comprised non-surgical (teeth scaling, root planing, and oral hygiene) and surgical methods (closed gingival curettage, modified Widman flap, and reconstructive surgery using autogenous bone marrow graft and canine amniotic membrane). The initial non-surgical treatment resulted in a periodontal recovery rate of 37.6% and was found effective for treatment of early periodontal disease based on resolution of gingivitis and reduction of periodontal probing depths. Surgical treatment by closed gingival curettage to eliminate the diseased pocket lining resulted in a recovery rate of 48.8% and proved effective in substantially reducing deep periodontal pockets. Open root planing following flap elevation resulted in a recovery rate of 85.4% and was effective for deep and refractory periodontal pockets. Autogenous bone graft implantation combined with canine amniotic

  20. Microbiologic, Pharmacokinetic, and Clinical Effects of Corneal Collagen Cross-Linking on Experimentally Induced Pseudomonas Keratitis in Rabbits.

    Science.gov (United States)

    Cosar, C Banu; Kucuk, Mutlu; Celik, Ekrem; Gonen, Tansu; Akyar, Isin; Serteser, Mustafa; Tokat, Fatma; Ince, Umit

    2015-10-01

    To determine the effects of corneal collagen cross-linking (CXL) on the penetration of topical 0.5% moxifloxacin, on the number of colony-forming units (CFUs) in the cornea, and on the clinical course in a rabbit eye model of experimentally induced Pseudomonas aeruginosa keratitis. In this prospective animal study, experimental Pseudomonas corneal ulcers were induced in 56 corneas of 28 albino New Zealand rabbits. The corneas were randomly divided into the following 4 groups: the control group (14 eyes), the MOX group (moxifloxacin) (14 eyes), the MOX + CXL group (14 eyes), and the CXL group (14 eyes). On day 4 of the experiment, the eyes in the control group were enucleated and CFU counting was performed. On day 10 of the experiment, all eyes were enucleated and CFU counting was performed. In the MOX and MOX + CXL groups, the moxifloxacin level in the cornea, aqueous humor, iris, plasma, and serum was measured by reverse-phase high-performance liquid chromatography. The difference in the corneal CFU count between the MOX group and the MOX + CXL group was not significant (P = 0.317). Clinical improvement was greatest in the MOX + CXL group (P < 0.001). The mean corneal moxifloxacin level was 0.391 ± 0.09 μg·mg in the MOX group versus 0.291 ± 0.09 μg·mg in the MOX + CXL group; as such, CXL did not have a significant effect on antibiotic penetrance (P = 0.386). Clinical improvement was greatest in the MOX + CXL group. The synergistic effect of CXL on corneal ulcer treatment is not through antibiotic penetrance.

  1. The role of potassium and other ions in the control of aldosterone synthesis

    International Nuclear Information System (INIS)

    Kenyon, C.J.; Shepherd, R.M.; Fraser, R.; Pediani, J.D.; Elder, H.Y.

    1991-01-01

    Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. The authors have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity

  2. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Choi, V.W.Y.; Lam, R.K.K.; Chong, E.Y.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Cheng, S.H. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2010-03-15

    The present work was devoted to designing the experimental setup and the associated procedures for alpha-particle-induced adaptive response in zebrafish embryos in vivo. Thin PADC films with a thickness of 16 mum were fabricated and employed as support substrates for holding dechorionated zebrafish embryos for alpha-particle irradiation from the bottom through the films. Embryos were collected within 15 min when the light photoperiod began, which were then incubated and dechorionated at 4 h post fertilization (hpf). They were then irradiated at 5 hpf by alpha particles using a planar {sup 241}Am source with an activity of 0.1151 muCi for 24 s (priming dose), and subsequently at 10 hpf using the same source for 240 s (challenging dose). The levels of apoptosis in irradiated zebrafish embryos at 24 hpf were quantified through staining with the vital dye acridine orange, followed by counting the stained cells under a florescent microscope. The results revealed the presence of the adaptive response in zebrafish embryos in vivo, and demonstrated the feasibility of the adopted experimental setup and procedures.

  3. The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    Peng-Fei Yu

    2011-01-01

    Full Text Available Danshensu (3-(3, 4-dihydroxyphenyl lactic acid, a water-soluble active component isolated from the root of Salvia miltiorrhiza Bunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1 (verapamil group or the same volume of normal saline (control group. Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1 by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS. The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

  4. Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

    Science.gov (United States)

    Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

    2018-04-01

    Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

  5. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  6. Mechanisms Underlying Vasorelaxation Induced in Rat Aorta by Galetin 3,6-Dimethyl Ether, a Flavonoid from Piptadenia stipulacea (Benth. Ducke

    Directory of Open Access Journals (Sweden)

    Cibério L. Macêdo

    2014-11-01

    Full Text Available In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe-induced contractions (pD2 = 5.36 ± 0.11 and 4.17 ± 0.10, respectively, suggesting the involvement of PKC and Phe pathways or α1 adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative contraction‑response curves, indicating a noncompetitive antagonism of α1 adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD2 = 5.50 ± 0.22 and 4.37 ± 0.12. The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA+. Furthermore, in the presence of apamin, glibenclamide, BaCl2 or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K+ channels (SKCa, ATP-sensitive K+ channels (KATP, inward rectifier K+ channels (Kir and voltage-dependent K+ channels (KV, respectively. FGAL inhibited and rightward shifted CaCl2-induced cumulative contraction-response curves in both depolarizing medium (high K+ and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca2+ influx through voltage-gated calcium channels (CaV and receptor operated channels (ROCs, respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca2+-free medium, indicating inhibition of Ca2+ release from the sarcoplasmic reticulum (SR. FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V. Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α1 adrenergic receptors, the non-selective opening of K+ channels, inhibition of Ca2+ influx through CaV or ROCs and the inhibition of intracellular Ca2+ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition.

  7. Regulation of adenosine deaminase (ADA) on induced mouse experimental autoimmune uveitis (EAU) ‡

    Science.gov (United States)

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J.; Sun, Deming

    2016-01-01

    Adenosine is an important regulator of the immune response and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies have shown that adenosine receptor (AR) agonists can be either anti- or pro-inflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 days post-immunization, shortly before EAU expression, but ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses and this effect was γδ T cell-dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help improve the design of ADA- and AR-targeted therapies. PMID:26856700

  8. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

    Science.gov (United States)

    Nowacka, Marta; Obuchowicz, Ewa

    2013-01-01

    Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

  9. Role of TRPV1 and ASIC3 channels in experimental occlusal interference-induced hyperalgesia in rat masseter muscle.

    Science.gov (United States)

    Xu, X X; Cao, Y; Ding, T T; Fu, K Y; Li, Y; Xie, Q F

    2016-04-01

    Masticatory muscle pain may occur following immediate occlusal alteration by dental treatment. The underlying mechanisms are poorly understood. Transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channel-3 (ASIC3) mediate muscle hyperalgesia under various pathologic conditions. We have developed a rat model of experimental occlusal interference (EOI) that consistently induces mechanical hyperalgesia in jaw muscles. Whether TRPV1 and ASIC3 mediate this EOI-induced hyperalgesia is unknown. Rat model of EOI-induced masseter hyperalgesia was established. Real-time polymerase chain reaction, Western blot and retrograde labelling combined with immunofluorescence were performed to evaluate the modulation of TRPV1 and ASIC3 expression in trigeminal ganglia (TGs) and masseter afferents of rats after EOI. The effects of intramuscular administration of TRPV1 and ASIC3 antagonists on the EOI-induced hyperalgesia in masseter muscle were examined. After EOI, gene expressions and protein levels of TRPV1 and ASIC3 in bilateral TGs were up-regulated. The percentage of ASIC3- (but not TRPV1-) positive neurons in masseter afferents increased after EOI. More small-sized and small to medium-sized masseter afferents expressed TRPV1 and ASIC3 separately following EOI. These changes peaked at day 7 and then returned to original status within 10 days after EOI. Intramuscular administration of the TRPV1 antagonist AMG-9810 partially reversed this mechanical hyperalgesia in masseter muscle. No improvement was exhibited after administration of the ASIC3 antagonist APETx2. Co-injection of AMG-9810 and APETx2 enhanced the effect of AMG-9810 administration alone. Peripheral TRPV1 and ASIC3 contribute to the development of the EOI-induced mechanical hyperalgesia in masseter muscle. © 2015 European Pain Federation - EFIC®

  10. Experimental induced avian E. coli salpingitis

    DEFF Research Database (Denmark)

    Olsen, Rikke Heidemann; Thøfner, Ida; Pors, Susanne Elisabeth

    2016-01-01

    Several types of Escherichia coli have been associated with extra-intestinal infections in poultry, however, they may vary significantly in their virulence potential. The aim of the present study was to investigate the virulence of five strains of E. coli obtained from different disease......) had a distinct ability to cause disease. Results of the study shows major differences in virulence of different strains of E. coli in ascending infections; however, there was no indication of tissue-specific adaptation, since strains obtained from lesions unrelated to the reproductive system were...... fully capable of causing experimental infection. In conclusion, the study provides evidence for the clinical outcome of infection with E. coli in poultry is largely influenced by the specific strain as well as individual host factors....

  11. TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.

    Science.gov (United States)

    Abassi, Zaid A; Barac, Yaron D; Kostin, Sawa; Roguin, Ariel; Ovcharenko, Elena; Awad, Hoda; Blank, Ayelet; Bar-Am, Orit; Amit, Tamar; Schaper, Jutta; Youdim, Moussa; Binah, Ofer

    2011-07-01

    Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.

  12. Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia.

    OpenAIRE

    Anno, T.; Kodama, I.; Shibata, S.; Toyama, J.; Yamada, K.

    1986-01-01

    Effects of hypoxia on atrioventricular conduction were investigated in the Langendorff-perfused isolated heart of the rabbit with various extracellular calcium concentrations ([Ca2+]) as well as in the presence of verapamil, nifedipine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) and chlorpromazine. The prolongation of the atrio-His (AH) interval by hypoxia for 7 min was greater with increasing [Ca2+]o ranging from 1.2 to 5.2 mM. At [Ca2+]o of over 3.2 mM under hypoxic condition...

  13. Cynodon dactylon extract as a preventive and curative agent in experimentally induced nephrolithiasis.

    Science.gov (United States)

    Atmani, F; Sadki, C; Aziz, M; Mimouni, M; Hacht, B

    2009-04-01

    Cynodon dactylon (Poaceae family) decoction was used in the treatment of kidney stones. However, no scientific study was undertaken so far to demonstrate the beneficial effect of the plant. Thus, the aim of the current study is to evaluate the effect of Cynodon aqueous extract as a preventive and curative agent in experimentally induced nephrolithiasis in a rat model. Ethylene glycol (EG) was used in the experiment to induce calcium oxalate (CaOx) deposition into kidneys. In preventive protocol, Cynodon decoction was administered in the same day with EG to evaluate the ability of the extract to prevent crystal deposition. However, in curative protocol, rats were first rendered nephrolithiasic and then the extract was administered to assess the ability of the plant to eliminate the pre-existing crystal deposition. In both protocols, urinary biochemical and other variables were measured during the course of the study. Crystalluria and renal histology were examined as well. The results showed that, in both protocols, all measured variables were similar for both the rat groups. Nevertheless, urinary biochemical analysis was apparently unaffected by the extract except oxalate in preventive protocol, and calcium, sodium, and potassium in curative protocol which were significantly highly excreted in treated rats compared to untreated animals. Crystalluria was characterized mostly by the presence of large quantities of CaOx monohydrate and CaOx dihydrate particles in untreated rats. However, crystalluria was mainly dominated by the presence of CaOx dihydrate particles with reduced size. The most apparent beneficial effect of Cynodon extract was seen in kidney tissues where reduced levels of CaOx deposition have been noticed especially in medullary and papillary sections from treated rats. We concluded that C. dactylon extract has beneficial effect in preventing and eliminating CaOx deposition into kidneys. Such findings provide a scientific explanation for its use in the

  14. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    Directory of Open Access Journals (Sweden)

    Saatsi Johanna

    2008-06-01

    Full Text Available Abstract Background Acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary

  15. Mechanism of S100b release from rat cortical slices determined under basal and stimulated conditions.

    Science.gov (United States)

    Gürsoy, Murat; Büyükuysal, R Levent

    2010-03-01

    Incubation of rat cortical slices in a medium that was not containing oxygen and glucose (oxygen-glucose deprivation, OGD) caused a 200% increase in the release of S100B. However, when slices were transferred to a medium containing oxygen and glucose (reoxygenation conditions, or REO), S100B release reached 500% of its control value. Neither inhibition of nitric oxide (NO) synthase by L-NAME nor addition of the NO donors sodium nitroprussid (SNP) or hydroxylamine (HA) to the medium altered basal S100B release. Similarly, the presence of SNP, HA or NO precursor L: -arginine in the medium, or inhibition of NO synthase by L-NAME also failed to alter OGD- and REO-induced S100B outputs. Moreover, individual inhibition of PKC, PLA(2) or PLC all failed to attenuate the S100B release determined under control condition or enhanced by either OGD or REO. Blockade of calcium channels with verapamil, chelating the Ca(+2) ions with BAPTA or blockade of sodium channels with tetrodotoxin (TTX) did not alter OGD- and REO-induced S100B release. In contrast to the pharmacologic manipulations mentioned above, glutamate and alpha-ketoglutarate added at high concentrations to the medium prevented both OGD- and REO-induced S100B outputs. These results indicate that neither NO nor the activation of PKC, PLA(2) or PLC seem to be involved in basal or OGD- and REO-induced S100B outputs. Additionally, calcium and sodium currents that are sensitive to verapamil and TTX, respectively, are unlikely to contribute to the enhanced S100B release observed under these conditions.

  16. Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

    Directory of Open Access Journals (Sweden)

    Aguilar-Nascimento J.E.

    1999-01-01

    Full Text Available The short chain fatty acids (SCFA are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10, 10% hypertonic glucose (N = 10 or SCFA (N = 10 until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean ± SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 ± 0.5 g than in the control (5.3 ± 2.1 g and glucose (5.2 ± 1.3 g groups (P<0.05. Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5] than in control (grade 9 [4-10] and glucose-treated (grade 9 [2-10] animals (P<0.01. Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01 and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05 animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis, whereas hypertonic glucose is of no benefit.

  17. Influence of serial electrical stimulations of perifornical and posterior hypothalamic orexin-containing neurons on regulation of sleep homeostasis and sleep-wakefulness cycle recovery from experimental comatose state and anesthesia-induced deep sleep.

    Science.gov (United States)

    Chijavadze, E; Chkhartishvili, E; Babilodze, M; Maglakelidze, N; Nachkebia, N

    2013-11-01

    The work was aimed for the ascertainment of following question - whether Orexin-containing neurons of dorsal and lateral hypothalamic, and brain Orexinergic system in general, are those cellular targets which can speed up recovery of disturbed sleep homeostasis and accelerate restoration of sleep-wakefulness cycle phases during some pathological conditions - experimental comatose state and/or deep anesthesia-induced sleep. Study was carried out on white rats. Modeling of experimental comatose state was made by midbrain cytotoxic lesions at intra-collicular level.Animals were under artificial respiration and special care. Different doses of Sodium Ethaminal were used for deep anesthesia. 30 min after comatose state and/or deep anesthesia induced sleep serial electrical stimulations of posterior and/or perifornical hypothalamus were started. Stimulation period lasted for 1 hour with the 5 min intervals between subsequent stimulations applied by turn to the left and right side hypothalamic parts.EEG registration of cortical and hippocampal electrical activity was started immediately after experimental comatose state and deep anesthesia induced sleep and continued continuously during 72 hour. According to obtained new evidences, serial electrical stimulations of posterior and perifornical hypothalamic Orexin-containing neurons significantly accelerate recovery of sleep homeostasis, disturbed because of comatose state and/or deep anesthesia induced sleep. Speed up recovery of sleep homeostasis was manifested in acceleration of coming out from comatose state and deep anesthesia induced sleep and significant early restoration of sleep-wakefulness cycle behavioral states.

  18. Role of taurine on acid secretion in the rat stomach

    Science.gov (United States)

    2011-01-01

    Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p taurine concentrations with cAMP was observed. Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach. PMID:21294907

  19. Role of taurine on acid secretion in the rat stomach

    Directory of Open Access Journals (Sweden)

    Ho Jau-Der

    2011-02-01

    Full Text Available Abstract Background Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA. Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. Methods The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. Results We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD, and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphat in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p Conclusions Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

  20. The transition time induced narrow linewidth of the electromagnetically induced transparency in caesium vapour

    International Nuclear Information System (INIS)

    Li Luming; Peng Xiang; Liu Cheng; Guo Hong; Chen Xuzong

    2004-01-01

    We observed a narrow linewidth (∼60 kHz) in a Doppler-broadened system showing electromagnetically induced transparency in caesium atomic vapour. The transition time induced reduction of the linewidth is illustrated both theoretically and experimentally

  1. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    DEFF Research Database (Denmark)

    Kavanagh, J. N.; Currell, F. J.; Timson, D. J.

    2010-01-01

    a further enhancement due to their annihilation at the end of the path. The work presented here aimed to establish and validate an experimental procedure for the quantification of plasmid and genomic DNA damage resulting from antiproton exposure. Immunocytochemistry was used to assess DNA damage in directly......Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offer...... and indirectly exposed human fibroblasts irradiated in both plateau and Bragg peak regions of a 126 MeV antiproton beam at CERN. Cells were stained post irradiation with an anti-γ-H2AX antibody. Quantification of the γ-H2AX foci-dose relationship is consistent with a linear increase in the Bragg peak region...

  2. Experimental Investigation Of Microbially Induced Corrosion Of Test Samples And Effect Of Self-assembled Hydrophobic Monolayers. Exposure Of Test Samples To Continuous Microbial Cultures, Chemical Analysis, And Biochemical Studies

    CERN Document Server

    Laurinavichius, K S

    1998-01-01

    Experimental Investigation Of Microbially Induced Corrosion Of Test Samples And Effect Of Self-assembled Hydrophobic Monolayers. Exposure Of Test Samples To Continuous Microbial Cultures, Chemical Analysis, And Biochemical Studies

  3. Histopathological findings for MR contrast-enhancement in BIO 14.6 hamsters with cardiomyopathy

    International Nuclear Information System (INIS)

    Munakata, Takehiko

    1998-01-01

    After administration of calcium antagonist (verapamil) and ACE-inhibitor (imidapril) to hamsters with cardiomyopathy, the results of contrast-enhanced MR imaging and the pathological findings at 25 weeks and 42 weeks of age were compared. The significance of MRI findings was examined in relation to histopathological findings in these hamsters. Hamsters were divided into two groups, a control group to which no drugs were administered and an experimental group that received the drugs. At 42 weeks, thickening of the left ventricular wall in the experimental group was significantly maintained in the ventricular septum compared with that in the control group. The fibrotic ratio for myocardium was greater at age 25 weeks than at age 7 weeks in the control group. In the experimental group receiving verapamil, the fibrotic ratio for myocardium was significantly smaller at age 25 weeks, whereas in the experimental group receiving imidapril, no significant decrease in fibrosis was observed at any age. In fibrotic regions, the number of regenerated capillaries per unit of cross-sectional area was significantly greater in the experimental group at age 25 weeks compared with the control group. There was a tendency for increased number of regenerated capillaries at age 42 weeks, but this was not statistically significant. A close correlation was observed between the signal intensity ratio in MRI and the fibrotic ratio and between the signal intensity ratio and the number of regenerated capillaries. It was observed that the results of MR imaging was influenced by not only fibrosis, but also by the regeneration of capillaries. Contrast-enhanced MR imaging, which can be used to assess the regeneration of capillaries, may prove to be of value for evaluation of response to therapy in patients with cardiomyopathy. (K.H.)

  4. Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.

    Science.gov (United States)

    Bayir, Yasin; Halici, Zekai; Keles, Mevlut Sait; Colak, Suat; Cakir, Ahmet; Kaya, Yusuf; Akçay, Fatih

    2011-11-18

    Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

    Science.gov (United States)

    Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

    2017-08-01

    pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

    Science.gov (United States)

    Iacovides, S; Avidon, I; Baker, F C

    2015-07-01

    Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

  7. Effect of taurine on calcium accumulation in resting and depolarised insect synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Whitton, P.S.; Nicholson, R.A.; Strang, R.H.

    1988-06-01

    The effect of taurine (2-aminoethanesulphonic acid) on /sup 45/Ca/sup 2 +/ accumulation in resting and depolarised synaptosomes obtained from the locust Schistocerca americana gregaria was studied. Taurine reduced /sup 45/Ca/sup 2 +/ accumulation in resting synaptosomes, and this effect was more pronounced when synaptosomes were depolarized with either high (K+) or veratridine. Veratridine-induced /sup 45/Ca/sup 2 +/ accumulation was not affected by either gamma-aminobutyric acid or leucine, but was reduced by both verapamil and tetrodotoxin.

  8. The effect of intracellular calcium level regulators on the synthesis of pollen tube callose in Oenothera biennis L.

    Directory of Open Access Journals (Sweden)

    Elżbieta Bednarska

    2014-01-01

    Full Text Available It is shown that callose synthesis in the Oenothera biennis pollen tube is regulated by the endogenous Ca2+ level. Calcium antagonists reduced the amount of callose in the wall above the tip of the pollen tube (Verapamil - calcium channels blocker and at the tube tip after stopping tube growth (La3+ - a Ca2+ substitute. Ruthenium red and ionophore A 23187, which raise the Ca 21 level in the cytoplasm, induced callose synthesis at the tip of pollen tube.

  9. Tobacco experimental model to induce urinary bladder neoplasms

    Directory of Open Access Journals (Sweden)

    José Alexandre Colli Neto

    2014-01-01

    Full Text Available OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin and the concentration of carbon dioxide (CO2 confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

  10. Determination of ultra-short laser induced damage threshold of KH{sub 2}PO{sub 4} crystal: Numerical calculation and experimental verification

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian [Center for Precision Engineering, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001 (China); Department of Physics, The Ohio State University, 191 W. Woodruff Ave, Columbus, OH 43210 (United States); Chen, Mingjun, E-mail: chenmj@hit.edu.cn, E-mail: chowdhury.24@osu.edu; Wang, Jinghe; Xiao, Yong [Center for Precision Engineering, School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001 (China); Kafka, Kyle; Austin, Drake; Chowdhury, Enam, E-mail: chenmj@hit.edu.cn, E-mail: chowdhury.24@osu.edu [Department of Physics, The Ohio State University, 191 W. Woodruff Ave, Columbus, OH 43210 (United States)

    2016-03-15

    Rapid growth and ultra-precision machining of large-size KDP (KH{sub 2}PO{sub 4}) crystals with high laser damage resistance are tough challenges in the development of large laser systems. It is of high interest and practical significance to have theoretical models for scientists and manufacturers to determine the laser-induced damage threshold (LIDT) of actually prepared KDP optics. Here, we numerically and experimentally investigate the laser-induced damage on KDP crystals in ultra-short pulse laser regime. On basis of the rate equation for free electron generation, a model dedicated to predicting the LIDT is developed by considering the synergistic effect of photoionization, impact ionization and decay of electrons. Laser damage tests are performed to measure the single-pulse LIDT with several testing protocols. The testing results combined with previously reported experimental data agree well with those calculated by the model. By taking the light intensification into consideration, the model is successfully applied to quantitatively evaluate the effect of surface flaws inevitably introduced in the preparation processes on the laser damage resistance of KDP crystals. This work can not only contribute to further understanding of the laser damage mechanisms of optical materials, but also provide available models for evaluating the laser damage resistance of exquisitely prepared optical components used in high power laser systems.

  11. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ERα in the liver of male lizard Podarcis sicula

    International Nuclear Information System (INIS)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero; Aniello, Francesco; Limatola, Ermelinda

    2011-01-01

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E 2 treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 μg/μl in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ERα in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: → Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. → VTG and ERα genes are unexpressed in the liver of untreated male lizards Podarcis. → In the liver cells of NP-treated males the expression of both VTG and ERα occurs. → In treated males VTG synthesis is coupled with ERα expression as in breeding females. - NP-polluted diet induces the expression of ERα and VTG in the liver.

  12. Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

    Science.gov (United States)

    Lange, Sofie C; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S; Hirrlinger, Johannes; Bak, Lasse K

    2015-12-01

    We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

  13. Experimental comparison of models for ultrafast impact ionization is silicon

    DEFF Research Database (Denmark)

    Tarekegne, Abebe Tilahun; Iwaszczuk, Krzysztof; Jepsen, Peter Uhd

    2016-01-01

    We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses.......We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses....

  14. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

    International Nuclear Information System (INIS)

    Constantinou, Maria A.; Theocharis, Stamatios E.; Mikros, Emmanuel

    2007-01-01

    Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using 1 H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. 1 H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the 1 H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients

  15. Experimental intrauterine growth retardation.

    Science.gov (United States)

    van Marthens, E; Harel, S; Zamenshof, S

    1975-01-01

    The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

  16. Experimental Warming Aggravates Degradation-Induced Topsoil Drought in Alpine Meadows of The Qinghai-Tibetan Plateau

    Science.gov (United States)

    Xue, X.

    2017-12-01

    Climatic warming is presumed to cause topsoil drought by increasing evapotranspiration and water infiltration, and by progressively inducing land degradation in alpine meadows of the Qinghai-Tibetan Plateau. However, how soil moisture and temperature patterns of degraded alpine meadows respond to climate warming remains unclear. A six-year continuous warming experiment was carried out in both degraded and undegraded alpine meadows in the source region of the Yangtze River. The goal was to identify the effects of climatic warming and land degradation on soil moisture (θ), soil surface temperature (Tsfc), and soil temperature (Ts). In the present study, land degradation significantly reduced θ by 4.5-6.1% at a depth of 0-100 cm (P soil surface. Experimental warming aggravated topsoil drought caused by land degradation, intensified the magnitude of degradation, and caused a positive feedback in the degraded alpine meadow ecosystem. Therefore, an immediate need exists to restore degraded alpine meadow grasslands in the Qinghai-Tibetan Plateau in anticipation of a warmer future.

  17. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  18. Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

    Science.gov (United States)

    Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

    2005-01-01

    The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

  19. Extension of the energy range of experimental activation cross-sections data of deuteron induced nuclear reactions on indium up to 50MeV.

    Science.gov (United States)

    Tárkányi, F; Ditrói, F; Takács, S; Hermanne, A; Ignatyuk, A V

    2015-11-01

    The energy range of our earlier measured activation cross-sections data of longer-lived products of deuteron induced nuclear reactions on indium were extended from 40MeV up to 50MeV. The traditional stacked foil irradiation technique and non-destructive gamma spectrometry were used. No experimental data were found in literature for this higher energy range. Experimental cross-sections for the formation of the radionuclides (113,110)Sn, (116m,115m,114m,113m,111,110g,109)In and (115)Cd are reported in the 37-50MeV energy range, for production of (110)Sn and (110g,109)In these are the first measurements ever. The experimental data were compared with the results of cross section calculations of the ALICE and EMPIRE nuclear model codes and of the TALYS 1.6 nuclear model code as listed in the on-line library TENDL-2014. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Ab-initio modeling of an iron laser-induced plasma: Comparison between theoretical and experimental atomic emission spectra

    International Nuclear Information System (INIS)

    Colgan, J.; Judge, E.J.; Kilcrease, D.P.; Barefield, J.E.

    2014-01-01

    We report on efforts to model the Fe emission spectrum generated from laser-induced breakdown spectroscopy (LIBS) measurements on samples of pure iron oxide (Fe 2 O 3 ). Our modeling efforts consist of several components. We begin with ab-initio atomic structure calculations performed by solving the Hartree–Fock equations for the neutral and singly ionized stages of Fe. Our energy levels are then adjusted to their experimentally known values. The atomic transition probabilities and atomic collision quantities are also computed in an ab-initio manner. We perform LTE or non-LTE calculations that generate level populations and, subsequently, an emission spectrum for the iron plasma for a range of electron temperatures and electron densities. Such calculations are then compared to the experimental spectrum. We regard our work as a preliminary modeling effort that ultimately strives towards the modeling of emission spectra from even more complex samples where less atomic data are available. - Highlights: • LIBS plasma of iron oxide • Ab-initio theoretical Modeling • Discussion of LTE versus non-LTE criteria and assessment • Boltzmann plots for Fe—determination of when LTE is a valid assumption • Emission spectra for Fe—comparison of theoretical modeling and measurement: good agreement obtained

  1. Experimental evaluation of neural probe’s insertion induced injury based on digital image correlation method

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenguang, E-mail: zhwg@sjtu.edu.cn; Ma, Yakun; Li, Zhengwei [State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-01-15

    Purpose: The application of neural probes in clinic has been challenged by probes’ short lifetime when implanted into brain tissue. The primary goal is to develop an evaluation system for testing brain tissue injury induced by neural probe’s insertion using microscope based digital image correlation method. Methods: A brain tissue phantom made of silicone rubber with speckle pattern on its surface was fabricated. To obtain the optimal speckle pattern, mean intensity gradient parameter was used for quality assessment. The designed testing system consists of three modules: (a) load module for simulating neural electrode implantation process; (b) data acquisition module to capture micrographs of speckle pattern and to obtain reactive forces during the insertion of the probe; (c) postprocessing module for extracting tissue deformation information from the captured speckle patterns. On the basis of the evaluation system, the effects of probe wedge angle, insertion speed, and probe streamline on insertion induced tissue injury were investigated. Results: The optimal quality speckle pattern can be attained by the following fabrication parameters: spin coating rate—1000 r/min, silicone rubber component A: silicone rubber component B: softener: graphite = 5 ml: 5 ml: 2 ml: 0.6 g. The probe wedge angle has a significant effect on tissue injury. Compared to wedge angle 40° and 20°, maximum principal strain of 60° wedge angle was increased by 40.3% and 87.5%, respectively; compared with a relatively higher speed (500 μm/s), the maximum principle strain within the tissue induced by slow insertion speed (100 μm/s) was increased by 14.3%; insertion force required by probe with convex streamline was smaller than the force of traditional probe. Based on the experimental results, a novel neural probe that has a rounded tip covered by a biodegradable silk protein coating with convex streamline was proposed, which has both lower insertion and micromotion induced tissue

  2. Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits.

    Science.gov (United States)

    Stitt, J T; Shimada, S G

    1991-09-01

    We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30-60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade.

  3. Low dose radiation induced protein and its experimental and ophthalmic clinical research

    International Nuclear Information System (INIS)

    Shen Wei; Su Liaoyuan; Liu Fenju; Ding Jie; Li Longbiao; Pan Chengsi

    2001-01-01

    The protective effects of low dose radiation (LDR) induced protein on cellular impairments caused by some harmful chemical and physical factors were studied. Male Kunming mice were irradiated with LDR, then the spleen cells of the mice were broken with ultrasonic energy and then ultracentrifugalized. The supernatant solution contained with LDR induced protein. The newly emerging protein was detected by gel filtration and its molecular weight was determined by gel electrophoresis. The content of newly emerging protein (LDR induced protein) was determined by Lowry's method. The method of isotope incorporation was used to observe the biological activity and its influence factors, the protective effects of LDR induced protein on the cells impaired by irradiating with ultraviolet (UV), high doses of 60 Co γ-rays and exposed to heat respectively, and the stimulative effects of LDR induced protein on human peripheral blood lymphocytes. Newly emerging protein has been observed in the experiment. The molecular weight of the protein is in the region 76.9 KD+- - 110.0 KD+-, the yield of the protein was 613.33 +- 213.42 μg per 3 x 10 7 spleen cells. DPM values (isotope were incorporated) of normal and injured mice spleen cells increased significantly after stimulating with the solution contained LDR induced protein. It is concluded that LDR induced protein could be obtained from mice spleen cells exposed to 5 - 15 cGy radiation for 2 - 16 h. The protein had biological activity and was able to stimulate the transformation of the spleen cells in vitro. It had obvious protective effects on some impaired cells caused by high dose radiation, UV radiation, heat and so on. It also had stimulative effects on the transformation of peripheral blood T and B lymphocytes of healthy individual and patients with eye diseases. It indicates that LDR induced protein increased immune function of human

  4. Increase vs. decrease of calcium uptake by isolated heart cells induced by H2O2 vs. HOCl

    International Nuclear Information System (INIS)

    Kaminishi, T.; Matsuoka, T.; Yanagishita, T.; Kako, K.J.

    1989-01-01

    Adult rat heart myocytes were labeled rapidly with exogenous [45Ca2+]. Addition of 2.5 mM H2O2 to the heart cell suspension raised the content of rapidly exchangeable intracellular Ca2+ twofold, whereas addition of 1-30 mM HOCl decreased the Ca2+ content. The H2O2-induced increase in Ca2+ content was dependent on the medium Na+, pH, and temperature but was not significantly affected by addition of verapamil, diltiazem, amiloride, or 3-aminobenzamide. The [3H]ouabain binding to myocytes was suppressed by H2O2, whereas the Ca2+ efflux from myocytes was not influenced. An uncoupler, carbonyl cyanide m-chlorophenylhydrazone, reduced Ca2+ content, implying that the H2O2-induced change in Ca2+ content was not directly related to ATP depletion. On the other hand, the H2O2-induced Ca2+ accumulation in myocytes was prevented by deferoxamine or o-phenanthroline. These results suggest that H2O2 inhibited Na+-K+-ATPase, resulting in an increase in intracellular Na+ concentration and stimulation of sarcolemmal Na+-Ca2+ exchange activity, which caused a transient net Ca2+ influx into myocytes. By contrast, HOCl decreased the Ca2+ content of the rapidly exchangeable pool below control levels and this action of HOCl was antagonized by 1,4-dithiothreitol. HOCl accelerated Ca2+ efflux from myocytes. Ca2+ uptake and Ca2+-ATPase of the isolated sarcoplasmic reticular (SR) fraction were highly sensitive to the action of HOCl. Ca2+ uptake by intracellular sites, studied with myocytes permeabilized with digitonin, was inhibited by both H2O2 and HOCl. Thus these results suggest that HOCl inhibits the SR Ca2+ pump, resulting in the observed acceleration of Ca2+ efflux from and decline in Ca2+ content of myocytes

  5. Wild Vervet Monkeys Trade Tolerance and Specific Coalitionary Support for Grooming in Experimentally Induced Conflicts.

    Science.gov (United States)

    Borgeaud, Christèle; Bshary, Redouan

    2015-11-16

    Grooming is a key social behavior in many primate species. Research has focused on three important aspects: the short- and long-term trading patterns of grooming for itself and/or for other commodities like tolerance or coalitionary support, the issue of whether exchanges are a convincing example for reciprocity, and what decision rules underlie trading. These issues remain largely unresolved due to the correlative nature of observational studies and the rarity of experimental studies. Here, we present a new experimental paradigm to address these questions in wild vervet monkeys (Chlorocebus pygerythrus). Adult females were first trained to approach a personal box, identifiable by unique color patterns, to access high-quality food. During the experiments, two boxes were placed next to each other to induce conflict through forced proximity. We found that while dominants were generally more tolerant toward bonded individuals, recent grooming increased tolerance independently of relationship quality. The latter result shows that vervet monkeys traded grooming for short-term tolerance, where dominants used a direct-reciprocity decision rule. In contrast, females invariably supported the higher-ranking opponent in a conflict, independently of who was the recent grooming partner. Nevertheless, recent grooming increased the probability that a female supported the partner during conflicts with a low-ranking third party. Thus, females' decisions about coalitionary support seem to integrate information about the current social hierarchy with recent grooming events. In conclusion, decision rules underlying trading of grooming for other commodities involve a variety of timescales and factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Experimental application of QCD antennas

    Energy Technology Data Exchange (ETDEWEB)

    Bobrovskyi, Sergei

    2010-02-15

    A serious problem in searches for new physics at the LHC is the rejection of QCD induced multijet events. In this thesis the formalism of QCD antenna variables based on the SPHEL approximation of QCD matrix elements is applied for the rst time on experimentally reconstructed jets in order to discriminate QCD from supersymmetric processes. The new observables provide additional information with respect to traditional event shape variables. Albeit correlated with experimentally measured missing transverse energy, the variables can be used to improve the signal to background ratio. (orig.)

  7. Experimental application of QCD antennas

    International Nuclear Information System (INIS)

    Bobrovskyi, Sergei

    2010-02-01

    A serious problem in searches for new physics at the LHC is the rejection of QCD induced multijet events. In this thesis the formalism of QCD antenna variables based on the SPHEL approximation of QCD matrix elements is applied for the rst time on experimentally reconstructed jets in order to discriminate QCD from supersymmetric processes. The new observables provide additional information with respect to traditional event shape variables. Albeit correlated with experimentally measured missing transverse energy, the variables can be used to improve the signal to background ratio. (orig.)

  8. The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

    LENUS (Irish Health Repository)

    Lyng, F M

    2006-04-01

    Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of

  9. A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Giovanna Franconi

    2013-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment.

  10. Current status of antiproton impact ionization of atoms and molecules: theoretical and experimental perspectives

    DEFF Research Database (Denmark)

    Kirchner, Tom; Knudsen, Helge

    2011-01-01

    Experimental and theoretical progress in the field of antiproton-impact-induced ionization of atoms and molecules is reviewed. We describe the techniques used to measure ionization cross sections and give an overview of the experimental results supplemented by tables of all existing data. An atte......Experimental and theoretical progress in the field of antiproton-impact-induced ionization of atoms and molecules is reviewed. We describe the techniques used to measure ionization cross sections and give an overview of the experimental results supplemented by tables of all existing data...

  11. Host response in bovine mastitis experimentally induced with Staphylococcus chromogenes.

    Science.gov (United States)

    Simojoki, H; Orro, T; Taponen, S; Pyörälä, S

    2009-02-16

    An experimental infection model was developed to study host response to intramammary infection in cows caused by Staphylococcus chromogenes. CNS intramammary infections have become very common in modern dairy herds, and they can remain persistent in the mammary gland. More information would be needed about the pathophysiology of CNS mastitis, and an experimental mastitis model is a means for this research. Six primiparous Holstein-Friesian cows were challenged with S. chromogenes 4 weeks after calving. One udder quarter of each cow was inoculated with 2.1 x 10(6)cfu of S. chromogenes. All cows became infected and clinical signs were mild. Milk production of the challenged quarter decreased on average by 16.3% during 7 days post-challenge. Cows eliminated bacteria in a few days, except for one cow which developed persistent mastitis. Milk indicators of inflammation, SCC and N-acetyl-beta-D-glucosaminidase (NAGase) returned to normal within a week. Milk NAGase activity increased moderately, which reflects minor tissue damage in the udder. Concentrations of serum amyloid A (SAA) and milk amyloid A (MAA) were both elevated at 12h PC. MAA was affected by the milking times, and was at its highest before the morning milking. In our experimental model, systemic acute phase protein response with SAA occurred as an on-off type reaction. In conclusion, this experimental model could be used to study host response in CNS mastitis caused by the main CNS species and also for comparison of the host response in a mild intramammary infection and in more severe mastitis models.

  12. Experimental investigation of localized stress-induced leakage current distribution in gate dielectrics using array test circuit

    Science.gov (United States)

    Park, Hyeonwoo; Teramoto, Akinobu; Kuroda, Rihito; Suwa, Tomoyuki; Sugawa, Shigetoshi

    2018-04-01

    Localized stress-induced leakage current (SILC) has become a major problem in the reliability of flash memories. To reduce it, clarifying the SILC mechanism is important, and statistical measurement and analysis have to be carried out. In this study, we applied an array test circuit that can measure the SILC distribution of more than 80,000 nMOSFETs with various gate areas at a high speed (within 80 s) and a high accuracy (on the 10-17 A current order). The results clarified that the distributions of localized SILC in different gate areas follow a universal distribution assuming the same SILC defect density distribution per unit area, and the current of localized SILC defects does not scale down with the gate area. Moreover, the distribution of SILC defect density and its dependence on the oxide field for measurement (E OX-Measure) were experimentally determined for fabricated devices.

  13. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ER{alpha} in the liver of male lizard Podarcis sicula

    Energy Technology Data Exchange (ETDEWEB)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Aniello, Francesco [Department of Biological Sciences, Genetic and Molecular Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Limatola, Ermelinda, E-mail: limatola@unina.it [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy)

    2011-05-15

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E{sub 2} treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 {mu}g/{mu}l in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ER{alpha} in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: > Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. > VTG and ER{alpha} genes are unexpressed in the liver of untreated male lizards Podarcis. > In the liver cells of NP-treated males the expression of both VTG and ER{alpha} occurs. > In treated males VTG synthesis is coupled with ER{alpha} expression as in breeding females. - NP-polluted diet induces the expression of ER{alpha} and VTG in the liver.

  14. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    International Nuclear Information System (INIS)

    Ishikawa, S.; Okada, K.; Saito, T.

    1988-01-01

    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ([Ca2+]i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased [Ca2+] significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of [Ca2+]i depended on the intracellular Ca pool, since an AVP-induced rise in [Ca2+]i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased 45 Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells

  15. Experimental study on the fragmentation of Adenine and Porphyrin molecules induced by low energy multicharged ion impact

    International Nuclear Information System (INIS)

    Li, B.

    2010-01-01

    Since the dissociation of small molecules might play key roles in the understanding of radiation induced damages of living tissues at the primary steps and at the molecular levels, fragmentation dynamics of small biomolecules have drawn much attention. The knowledge of the internal energy is of fundamental importance for understanding its fragmentation dynamics following external excitation. For a long time however, it was difficult to measure this parameter in coincidence with the fragmentation patterns until the development of CIDEC (Collision Induced Dissociation under Energy Control) method in 2007. In this work, the CIDEC method was extended to study the fragmentation of gas-phase biomolecules adenine (Ade: H 5 C 5 N 5 ) and porphyrin chloride FeTPPCl (C 44 H 28 N 4 FeCl). The population distribution for each dissociation channel as a function of the excitation energy of the parent molecular ions at a well-determined initial charge state has been experimentally determined, which could shed some light on the fragmentation dynamics of these molecules. In collisions between Cl + and Ade at 3 keV, the fragmentation pattern of Ade 2+ is dominated by the loss of H 2 CN + and the successive emission of HCN. The energy distribution of the parent dication confirms the successive emission dynamics. A specific decay channel is observed, i.e. the emission of a charged H 2 CN + followed by the emission of HC 2 N 2 . The measured mean excitation energies of this channel and other competitive channels are compared. In Kr 8+ - FeTPPCl collisions at 80 keV, parent ions FeTPPCL 1+,2+,3+ are observed, along with the corresponding decay patterns. It is found that, in the first step the dominant low-energy-cost decay channel is the emission of Cl 0 independent of the initial charge state of FeTPPCl r+ . For the resulted dication FeTPP 2+ , the dominant fragmentation channel is the neutral evaporation; for the tri-cation however, the dominant fragmentation channel is the

  16. Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

    Science.gov (United States)

    Pandey, Shruti; Garabadu, Debapriya

    2017-07-01

    Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

  17. Comparative study of the effects of experimentally induced hypothyroidism and hyperthyroidism in some brain regions in albino rats.

    Science.gov (United States)

    El-Bakry, A M; El-Gareib, A W; Ahmed, R G

    2010-08-01

    Thyroid hormones (THs) play a crucial role in the development and physiological functioning of different body organs especially the brain. Therefore, the objective of this study was to show the histopathological effects of the different thyroid states on some brain regions (cerebrum and cerebellum) and the skeletal features of their newborns during the postnatal development from the 1st to 3rd week. The female white albino rats were allocated into 3 groups as follows: the experimental hypothyroidism group is induced by 0.02% methimazole (MMI) (w/v) in drinking water, while the experimental hyperthyroidism group is performed by exogenous T4 [from 50 to 200microg/kg body weight intragastric administration beside adding 0.002% T4 (w/v) to the drinking water] from the gestation day 1 to lactation day 21 and control group which received tap water. As well, both maternal hypo- and hyperthyroidism caused some malformation and developmental defects in the cerebellar and cerebral cortex of their newborns along the duration of the experiment. These degenerative symptoms became more prominent and widely spread at the 3rd postnatal week. Concomitantly, there were some degeneration, deformation and severe growth retardation in neurons of these regions in both treated groups throughout the experimental period. Moreover, the skeletal features of these newborns were accelerated in hyperthyroid group while these maturations were delayed partially in hypothyroid ones during the examined periods. These alterations, on both treated groups, were age and dose dependent. Thus, further studies need to be done to emphasize this concept. Published by Elsevier Ltd.

  18. A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis.

    Science.gov (United States)

    Elburki, Muna S; Rossa, Carlos; Guimarães-Stabili, Morgana R; Lee, Hsi-Ming; Curylofo-Zotti, Fabiana A; Johnson, Francis; Golub, Lorne M

    2017-08-01

    The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

  19. An experimental investigation of proton-induced phenomena in krypton

    International Nuclear Information System (INIS)

    Mulders, J.J.L.

    1985-01-01

    In this thesis proton-induced phenomena in krypton gas are described. The considered reactions of protons on krypton are both nuclear and atomic. The nuclear conversion processes mainly result in the production of several Rb radioisotopes, such as 81 Rb that is used in 81 Rb-sup(81m)Kr generator systems for medical diagnostics. The irradiation of krypton gas (natural composition) with protons of about 26 MeV can be used for the routine production of 81 Rb from the direct production reaction 82 Kr(p,2n) 81 Rb and from the indirect reaction 82 Kr(p,2n)sup(81m)Rb → 81 Rb. To determine the scattering of protons in krypton gas targets a quantitative autoradiographic technique was developed. Proton profiles have been determined from the proton-induced activity distribution on a copper foil. For the on-line detection of produced Rb radioisotopes several optical detection techniques were investigated. (Auth.)

  20. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    International Nuclear Information System (INIS)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Gutiérrez, Silvina; Torres, Alicia Inés; De Paul, Ana Lucía

    2013-01-01

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  1. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela [Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Gutiérrez, Silvina; Torres, Alicia Inés [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); De Paul, Ana Lucía, E-mail: adepaul@cmefcm.uncor.edu [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina)

    2013-11-15

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  2. An Experimental Study of Roughness-Induced Instabilities in a Supersonic Boundary Layer

    Science.gov (United States)

    Kegerise, Michael A.; King, Rudolph A.; Choudhari, Meelan; Li, Fei; Norris, Andrew

    2014-01-01

    Progress on an experimental study of laminar-to-turbulent transition induced by an isolated roughness element in a supersonic laminar boundary layer is reported in this paper. Here, the primary focus is on the effects of roughness planform shape on the instability and transition characteristics. Four different roughness planform shapes were considered (a diamond, a circle, a right triangle, and a 45 degree fence) and the height and width of each one was held fixed so that a consistent frontal area was presented to the oncoming boundary layer. The nominal roughness Reynolds number was 462 and the ratio of the roughness height to the boundary layer thickness was 0.48. Detailed flow- field surveys in the wake of each geometry were performed via hot-wire anemometry. High- and low-speed streaks were observed in the wake of each roughness geometry, and the modified mean flow associated with these streak structures was found to support a single dominant convective instability mode. For the symmetric planform shapes - the diamond and circular planforms - the instability characteristics (mode shapes, growth rates, and frequencies) were found to be similar. For the asymmetric planform shapes - the right-triangle and 45 degree fence planforms - the mode shapes were asymmetrically distributed about the roughness-wake centerline. The instability growth rates for the asymmetric planforms were lower than those for the symmetric planforms and therefore, transition onset was delayed relative to the symmetric planforms.

  3. Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

    Science.gov (United States)

    Bakris, George; Molitch, Mark; Zhou, Qian; Sarafidis, Pantelis; Champion, Annette; Bacher, Peter; Sowers, James R

    2008-01-01

    Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

  4. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

    Directory of Open Access Journals (Sweden)

    Balan Rajan

    2015-06-01

    Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

  5. Collagen V-induced nasal tolerance downregulates pulmonary collagen mRNA gene and TGF-beta expression in experimental systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Parra Edwin R

    2010-01-01

    Full Text Available Abstract Background The purpose of this study was to evaluate collagen deposition, mRNA collagen synthesis and TGF-beta expression in the lung tissue in an experimental model of scleroderma after collagen V-induced nasal tolerance. Methods Female New Zealand rabbits (N = 12 were immunized with 1 mg/ml of collagen V in Freund's adjuvant (IM. After 150 days, six immunized animals were tolerated by nasal administration of collagen V (25 μg/day (IM-TOL daily for 60 days. The collagen content was determined by morphometry, and mRNA expressions of types I, III and V collagen were determined by Real-time PCR. The TGF-beta expression was evaluated by immunostaining and quantified by point counting methods. To statistic analysis ANOVA with Bonferroni test were employed for multiple comparison when appropriate and the level of significance was determined to be p Results IM-TOL, when compared to IM, showed significant reduction in total collagen content around the vessels (0.371 ± 0.118 vs. 0.874 ± 0.282, p p p = 0.026. The lung tissue of IM-TOL, when compared to IM, showed decreased immunostaining of types I, III and V collagen, reduced mRNA expression of types I (0.10 ± 0.07 vs. 1.0 ± 0.528, p = 0.002 and V (1.12 ± 0.42 vs. 4.74 ± 2.25, p = 0.009 collagen, in addition to decreased TGF-beta expression (p Conclusions Collagen V-induced nasal tolerance in the experimental model of SSc regulated the pulmonary remodeling process, inhibiting collagen deposition and collagen I and V mRNA synthesis. Additionally, it decreased TGF-beta expression, suggesting a promising therapeutic option for scleroderma treatment.

  6. Experimental determination of the temperature range of AlO molecular emission in laser-induced aluminum plasma in air

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xueshi; Motto-Ros, Vincent [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon Villeurbanne (France); Lei, Wenqi [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon Villeurbanne (France); State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062 (China); Zheng, Lijuan [State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062 (China); Yu, Jin, E-mail: jin.yu@univ-lyon1.fr [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon Villeurbanne (France); Key Laboratory for Laser Plasmas (Ministry of Education), Department of Physics and Astrophysics, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2014-09-01

    Measurements with laser-induced breakdown spectroscopy (LIBS) usually take place in the atmospheric air. For quantitative analysis of metallic elements, oxidation may represent an important issue which can significantly modify the stoichiometry of the plasma. Molecule formation in plasma should be therefore studied and taken into account in the LIBS practice. In this work, we experimentally investigated the temporal evolution and transformation of the plasma induced on an aluminum target by a nanosecond infrared (1064 nm) laser in the atmospheric air, in terms of its temperatures over a large interval of time from hundreds of nanoseconds to tens of microseconds. Such evolution was then correlated to the temporal evolution of the emission intensity from AlO molecules in the ablation plume. In particular, for a given ablation laser pulse energy, the appearance of the molecular emission while the plume cools down allows determining a minimal delay, τ{sub min}, which corresponds to a maximal value of the temperature, T{sub max}, below which the molecular emission begins to be clearly observed and to grow as a function of the delay. Such delay or such temperature indicates the longest delay or the lowest temperature for laser-induced plasma to be suitable for a correct analysis of metallic elements without significant influence of the alternation of the stoichiometry by oxidation. In our experiment, the values of τ{sub min} and T{sub max} have been determined for a range of ablation laser pulse energies from 5 mJ to 50 mJ. These values lie respectively in the range of 3 to 15 μs for τ{sub min}, and 4500 K to 6600 K in terms of the molecule temperature for T{sub max}. Beyond the practical interest for LIBS, our results provide also insights to the kinetics of the AlO molecule formation in laser-induced plasma. - Highlights: • Determination of the temperatures in laser-induced plasma up to tens of microseconds • Determination of the molecule temperature by fitting

  7. Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

    Science.gov (United States)

    Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

    2017-01-01

    It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

  8. Immunization with Recombinantly Expressed LRP4 Induces Experimental Autoimmune Myasthenia Gravis in C57BL/6 Mice.

    Science.gov (United States)

    Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem

    2017-07-01

    Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.

  9. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Inertial waves in a spherical shell induced by librations of the inner sphere: experimental and numerical results

    Energy Technology Data Exchange (ETDEWEB)

    Koch, S; Harlander, U; Egbers, C [Department of Aerodynamics and Fluid Mechanics, Brandenburg University of Technology Cottbus, Siemens-Halske-Ring 14, D-03046 Cottbus (Germany); Hollerbach, R, E-mail: uwe.harlander@tu-cottbus.de [Institute of Geophysics, ETH Zuerich, Sonneggstrasse 5, CH-8092 Zurich (Switzerland)

    2013-06-15

    We begin with an experimental investigation of the flow induced in a rotating spherical shell. The shell globally rotates with angular velocity {Omega}. A further periodic oscillation with angular velocity 0 Less-Than-Or-Slanted-Equal-To {omega} Less-Than-Or-Slanted-Equal-To 2{Omega}, a so-called longitudinal libration, is added on the inner sphere's rotation. The primary response is inertial waves spawned at the critical latitudes on the inner sphere, and propagating throughout the shell along inclined characteristics. For sufficiently large libration amplitudes, the higher harmonics also become important. Those harmonics whose frequencies are still less than 2{Omega} behave as inertial waves themselves, propagating along their own characteristics. The steady component of the flow consists of a prograde zonal jet on the cylinder tangent to the inner sphere and parallel to the axis of rotation, and increases with decreasing Ekman number. The jet becomes unstable for larger forcing amplitudes as can be deduced from the preliminary particle image velocimetry observations. Finally, a wave attractor is experimentally detected in the spherical shell as the pattern of largest variance. These findings are reproduced in a two-dimensional numerical investigation of the flow, and certain aspects can be studied numerically in greater detail. One aspect is the scaling of the width of the inertial shear layers and the width of the steady jet. Another is the partitioning of the kinetic energy between the forced wave, its harmonics and the mean flow. Finally, the numerical simulations allow for an investigation of instabilities, too local to be found experimentally. For strong libration amplitudes, the boundary layer on the inner sphere becomes unstable, triggering localized Goertler vortices during the prograde phase of the forcing. This instability is important for the transition to turbulence of the spherical shell flow. (paper)

  11. An improved method to experimentally determine temperature and pressure behind laser-induced shock waves at low Mach numbers

    International Nuclear Information System (INIS)

    Hendijanifard, Mohammad; Willis, David A

    2011-01-01

    Laser-matter interactions are frequently studied by measuring the propagation of shock waves caused by the rapid laser-induced material removal. An improved method for calculating the thermo-fluid parameters behind shock waves is introduced in this work. Shock waves in ambient air, induced by pulsed Nd : YAG laser ablation of aluminium films, are measured using a shadowgraph apparatus. Normal shock solutions are applied to experimental data for shock wave positions and used to calculate pressure, temperature, and velocity behind the shock wave. Non-dimensionalizing the pressure and temperature with respect to the ambient values, the dimensionless pressure and temperature are estimated to be as high as 90 and 16, respectively, at a time of 10 ns after the ablation pulse for a laser fluence of F = 14.5 J cm -2 . The results of the normal shock solution and the Taylor-Sedov similarity solution are compared to show that the Taylor-Sedov solution under-predicts pressure when the Mach number of the shock wave is small. At a fluence of 3.1 J cm -2 , the shock wave Mach number is less than 3, and the Taylor-Sedov solution under-predicts the non-dimensional pressure by as much as 45%.

  12. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

    Directory of Open Access Journals (Sweden)

    Kamaldeen A Muili

    Full Text Available The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

  13. Hexagonal boron nitride and graphene in-plane heterostructures: An experimentally feasible approach to charge-induced switchable CO{sub 2} capture

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Xin; Tahini, Hassan A.; Smith, Sean C., E-mail: sean.smith@unsw.edu.au

    2016-10-20

    Hexagonal boron nitride (h-BN) has been proposed as a sorbent material for charge-induced switchable CO{sub 2} capture. However, h-BN is a wide-gap semiconductor, hindering injection of the requisite charge. Here, we employ first-principle calculations to support the proposal that in-plane h-BN/graphene (P-BN/G) heterostructures, consisting of alternating strips of h-BN and graphene, may provide an experimentally feasible material platform for voltage-induced charging of h-BN strips to realize switchable CO{sub 2} capture. Our results show that a significant amount of injected negative charges are distributed onto h-BN strips of P-BN/G, such that CO{sub 2} capture/release can be simply controlled by switching on/off the charge states of P-BN/G system. At saturation CO{sub 2} capture coverage, the negatively charged P-BN/G heterostructures achieve CO{sub 2} capture capacities up to 2.27 × 10{sup 14} cm{sup −2}, which is twice that which can be achieved on stacked h-BN/graphene (S-BN/G) nanosheets.

  14. Costs and benefits of experimentally induced changes in the allocation of growth versus immune function under differential exposure to ectoparasites.

    Directory of Open Access Journals (Sweden)

    Natalia Pitala

    2010-05-01

    Full Text Available Ecological immunology has focused on the costs of investment in immunocompetence. However, understanding optimal resource allocation to immune defence requires also identification of its benefits, which are likely to occur only when parasites are abundant.We manipulated the abundance of parasitic hen fleas in blue tit (Cyanistes caeruleus nests, and supplemented their hosts, the nestlings, with methionine (a sulphur amino acid enhancing cell-mediated immunity during day 3-6. We found a significant interaction between these two experimental factors on the development of immune defences and growth rates. Only in parasitized nests did methionine supplementation boost immune (PHA response, and did nestling with experimentally increased immunocompetence show a relatively faster growth rate than control nestlings between days 6-9. Hence, the allocation of resources into immune defence and its growth-benefits are apparent only in presence of parasites. The main cost of methionine-induced increased allocation to the immune system was an increase in mortality, independently of ectoparasites. Nestlings in all treatments compensated initial growth reduction and all reached equal body size at day 16 (just prior to fledging, indicating a lack of long-term benefits. In addition, methionine treatment tended (P = 0.09 to lower circulating plasma immunoglobulin levels, possibly indicating a trade-off between the cell-mediated and humoral components of the immune system.We found no strong benefits of an increased investment in immunocompetence in a parasite-rich environment. Any deviation from the growth trajectory (due to changes in allocation induced by methionine is largely detrimental for survival. Hence, while costs are apparent identifying the benefits of investment in immunocompetence during ontogeny is challenging.

  15. Anti-fibrotic effects of Cuscuta chinensis with in vitro hepatic stellate cells and a thioacetamide-induced experimental rat model.

    Science.gov (United States)

    Kim, Jin Seoub; Koppula, Sushruta; Yum, Mun Jeong; Shin, Gwang Mo; Chae, Yun Jin; Hong, Seok Min; Lee, Jae Dong; Song, MinDong

    2017-12-01

    Cuscuta chinensis Lam. (Convolvulaceae) has been used as a traditional herbal remedy for treating liver and kidney disorders. Anti-fibrotic effects of C. chinensis extract (CCE) in cellular and experimental animal models were investigated. HSC-T6 cell viability, cell cycle and apoptosis were analysed using MTT assay, flow cytometry and Annexin V-FITC/PI staining techniques. Thioacetamide (TAA)-induced fibrosis model was established using Sprague Dawley rats (n = 10). Control, TAA, CCE 10 (TAA with CCE 10 mg/kg), CCE 100 (TAA with CCE 100 mg/kg) and silymarin (TAA with silymarin 50 mg/kg). Fibrosis was induced by TAA (200 mg/kg, i.p.) twice per week for 13 weeks. CCE and silymarin were administered orally two times per week from the 7th to 13th week. Fibrotic related gene expression (α-SMA, Col1α1 and TGF-β1) was measured by RT-PCR. Serum biomarkers, glutathione (GSH) and hydroxyproline were estimated by spectrophotometer using commercial kits. CCE (0.05 and 0.1 mg/mL) and silymarin (0.05 mg/mL) treatment significantly (p < 0.01 and p < 0.001) induced apoptosis (11.56%, 17.52% for CCE; 16.50% for silymarin, respectively) in activated HSC-T6 cells, compared with control group (7.26%). Further, rat primary HSCs showed changes in morphology with CCE 0.1 mg/mL treatment. In in vivo studies, CCE (10 and 100 mg/kg) treatment ameliorated the TAA-induced altered levels of serum biomarkers, fibrotic related gene expression, GSH, hydroxyproline significantly (p < 0.05-0.001) and rescued the histopathological changes. CCE can be developed as a potential agent in the treatment of hepatofibrosis.

  16. SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2016-01-01

    Full Text Available Sirtuin3 (SIRT3 is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH, we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

  17. Intra-arterial vasodilators to prevent radial artery spasm: a systematic review and pooled analysis of clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, Chun Shing, E-mail: shingkwok@doctors.org.uk [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Rashid, Muhammad [St. Helens & Knowsley Teaching Hospital (NHS) Trust, Whiston Hospital, Prescot (United Kingdom); Fraser, Doug [Manchester Heart Centre, Manchester Royal Infirmary (United Kingdom); Nolan, James [University Hospital of North Midlands, Stoke-on-Trent (United Kingdom); Mamas, Mamas [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Farr Institute, Institute of Population Health, University of Manchester, Manchester (United Kingdom)

    2015-12-15

    Objectives: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS. Background: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization. Methods: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion. Results: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5 mg of verapamil 12% (3 studies, 768 participants) but greater than 5 mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 μg (4%) and 200 μg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies. Conclusions: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5 mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS. - Highlights: • Radial artery spasm (RAS) causes procedural failure in transradial catheterization. • RAS may complicate 10–15% procedures undertaken through the radial approach. • We reviewed the efficacy of vasodilators that have been used to minimize RAS. • The pooled RAS rate was lowest with 5 mg of verapamil (4%) compared to placebo (12%). • The best combination of drugs to minimize RAS is nitroglycerine and verapamil.

  18. Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. II. Findings in experimentally induced ureteric stenosis

    International Nuclear Information System (INIS)

    Rohrschneider, W.K.; Becker, K.; Hoffend, J.; Clorius, J.H.; Darge, K.; Kooijman, H.; Troeger, J.

    2000-01-01

    Purpose. To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction in the piglet. Materials and methods. In 20 piglets unilateral ureteric stenosis was created operatively. Post-surgery repeated comparative examinations were obtained with MRU, diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US). MRU was performed as a combination study with a static 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA with frusemide administration. Results. MRU allowed complete depiction of the prestenotic urinary tract and of the stenosis in all cases. In 43 comparative studies MRU was superior to EU in 36, EU to MRU in 2. When single kidney function was calculated with both MRU and DRS, results were highly correlated (r = 0.92). When urinary excretion was compared, significant agreement was achieved with concordant findings in 86 % and slightly discordant results in 12 %. Conclusions. Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out - it does not require radiation and it permits functional-morphological correlation. (orig.)

  19. Inducibility of error-prone DNA repair in yeast

    International Nuclear Information System (INIS)

    Siede, W.; Eckardt, F.

    1984-01-01

    Whereas some experimental evidence suggests that mutagenesis in yeast after treatment with DNA-damaging agents involves inducible functions, a general-acting error-prone repair activity analogous to the SOS system of Escherichia coli has not yet been demonstrated. The current literature on the problem of inducibility of mutagenic repair in yeast is reviewed with emphasis on the differences in the experimental procedures applied. (orig.)

  20. Aquaporin-1 and aquaporin-3 expressions in the temporo-mandibular joint condylar cartilage after an experimentally induced osteoarthritis.

    Science.gov (United States)

    Meng, Juan-hong; Ma, Xu-chen; Li, Zhi-min; Wu, Deng-cheng

    2007-12-20

    Over 70% of the total tissue weight in the cartilage matrix consists of water, and the early-stage osteoarthritic cartilage is characterized by swelling. Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage. The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis (OA) in rats. An experimental temporomandibular joint OA was induced by partial discectomy in rats. The pathological characteristics of the normal, early-stage, and late-stage osteoarthritic TMJ cartilages were verified by histological techniques. The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis. The cartilage sections were incubated in primary polyclonal antibodies to AQP3; immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level. The mRNA expression levels of AQP1 and AQP3, analyzed using quantitative PCR, revealed that AQP3 mRNA was highly up-regulated in the OA cartilage, which was considered significant. There was no notable difference in the expression of AQP1 mRNA between OA and normal controls. With the progressing of the OA, the localization of the AQP3 protein was quite different from that of the normal cartilage. Compared to the normal cartilage, the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA, and were observed to appear frequently throughout the mid- and deep zone during the late-stage of OA. The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis. Further study of AQP3 function may provide new insight into the understanding of the

  1. Experimental investigation of ultraviolet laser induced plasma density and temperature evolution in air

    International Nuclear Information System (INIS)

    Thiyagarajan, Magesh; Scharer, John

    2008-01-01

    We present measurements and analysis of laser induced plasma neutral densities and temperatures in dry air by focusing 200 mJ, 10 MW high power, 193 nm ultraviolet ArF (argon fluoride) laser radiation to a 30 μm radius spot size. We examine these properties that result from multiphoton and collisional cascade processes for pressures ranging from 40 Torr to 5 atm. A laser shadowgraphy diagnostic technique is used to obtain the plasma electron temperature just after the shock front and this is compared with optical emission spectroscopic measurements of nitrogen rotational and vibrational temperatures. Two-color laser interferometry is employed to measure time resolved spatial electron and neutral density decay in initial local thermodynamic equilibrium (LTE) and non-LTE conditions. The radiating species and thermodynamic characteristics of the plasma are analyzed by means of optical emission spectroscopy (OES) supported by SPECAIR, a special OES program for air constituent plasmas. Core plasma rotational and vibrational temperatures are obtained from the emission spectra from the N 2 C-B(2+) transitions by matching the experimental spectrum results with the SPECAIR simulation results and the results are compared with the electron temperature just behind the shock wave. The plasma density decay measurements are compared with a simplified electron density decay model that illustrates the dominant three-and two-body recombination terms with good correlation

  2. Spontaneous progression of ligature induced peri-implantitis at implants with different surface roughness: an experimental study in dogs

    DEFF Research Database (Denmark)

    Berglundh, T; Gotfredsen, K; Zitzmann, N U

    2007-01-01

    : The aim of the current experiment was to study the progression of peri-implantitis around implants with different surface roughness. MATERIAL AND METHODS: In five beagle dogs, three implants with either a sandblasted acid-etched surface (SLA) or a polished surface (P) were installed bilaterally......BACKGROUND: Peri-implantitis is associated with the presence of submarginal plaque, soft-tissue inflammation and advanced breakdown of the supporting bone. The progression of peri-implantitis following varying periods of continuing plaque accumulation has been studied in animal models. OBJECTIVE...... in the edentulous premolar regions. After 3 months on a plaque control regimen, experimental peri-implantitis was induced by ligature placement and plaque accumulation was allowed to progress until about 40% of the height of the supporting bone had been lost. After this 4-month period, ligatures were removed...

  3. Experimental demonstration of squeezed-state quantum averaging

    DEFF Research Database (Denmark)

    Lassen, Mikael Østergaard; Madsen, Lars Skovgaard; Sabuncu, Metin

    2010-01-01

    We propose and experimentally demonstrate a universal quantum averaging process implementing the harmonic mean of quadrature variances. The averaged variances are prepared probabilistically by means of linear optical interference and measurement-induced conditioning. We verify that the implemented...

  4. Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

    OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

  5. Experimental study of induced staggered magnetic fields in dysprosium gallium garnet (DGG)

    International Nuclear Information System (INIS)

    Steiner, M.; Corliss, L.M.; Hastings, J.M.; Blume, M.; Giordano, N.; Wolf, W.P.

    1979-01-01

    Neutron diffraction techniques have been used to study induced staggered magnetic field effects in DGG. The application of a uniform magnetic field at temperatures much greater than the Neel temperature induces a significant amount of antiferromagnetic order. The temperature and field dependences of this effect are in good agreement with recent theoretical predicions

  6. Experimental carcinogenesis induced by incorporated plutonium

    International Nuclear Information System (INIS)

    Oghiso, Yoichi

    1999-01-01

    The carcinogenic effects of an alpha-emitter, 239 Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

  7. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring.

    Science.gov (United States)

    Abbott, David H; Bruns, Cristin R; Barnett, Deborah K; Dunaif, Andrea; Goodfriend, Theodore L; Dumesic, Daniel A; Tarantal, Alice F

    2010-11-01

    Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155-175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in

  8. Experimental validation of the design method to prevent flow-induced vibration in high Reynolds-number

    International Nuclear Information System (INIS)

    Sakai, Takaaki; Yamaguchi, Akira; Morisita, Masaki; Iwata, Koji

    1998-08-01

    The incident of sodium leakage from a main pipe of the secondary heat transport system of Monju fast breeder reactor was caused by the failure of a thermometer well. 'Flow-induced vibration design guide for thermometer wells' (express as 'design guide') was proposed by PNC Working Group to prevent the same cause of the sodium leak incident in future. On this report, applicability of the 'design guide' was estimated to plant conditions in high Reynolds-number(approximately 3x10 5 ∼ 3x10 6 ) involving the supercritical region, by measured data on a vortex synchronized vibration and a turbulence induced vibration. Experiments were performed for cylindrical and taper shaped types of test pieces. As results, reduced velocity (Vr) at onsets of the inline synchronized vibration were evaluated to be grater than 1.0 in the range of experimental conditions. Fluctuating drag and lift coefficients, which were evaluated from power spectrum of turbulence for Vr < 1.0 condition, were 0.01 ∼ 0.05 for drag direction and 0.04 ∼ 0.13 for lift direction. The fluctuating drag and lift coefficients used in the 'design guide' were estimated to be conservative by comparison with these data. Correlation lengths for a cylinder and a taper shaped one in the high Reynolds-number region were estimated to be 1.6 times of the diameter(D) in the maximum case. The measured value of correlation length is enough smaller than the 'design guide' value of 3.0D. Displacement amplitudes of test pieces for Vr < 1.0 conditions were enough smaller (fives times) than calculated values based on the 'design guide'. Consequently, the applicability of the design guide' was confirmed in the range of experiments involving the super critical Reynolds-number region. (author)

  9. Nyctanthes arbor-tristis Ameliorated FCA-Induced Experimental Arthritis: A Comparative Study among Different Extracts

    Science.gov (United States)

    Uroos, Maliha; Sattar, Shumaila; Umer, Nigarish; Sharif, Ahsan

    2017-01-01

    Nyctanthes arbor-tristis (NAT) is commonly used traditionally for the treatment of rheumatism and inflammatory diseases. Current study evaluates the antiarthritic potential of NAT using Freund's adjuvant-induced arthritic rat model. Treatments with methanolic, ethyl acetate, and n-hexane extracts were continued for consecutive 20 days. Macroscopic arthritic scoring and water displacement plethysmometry were used to evaluate arthritic development. Hematological and biochemical parameters were investigated and ankle joints were processed for histopathological evaluation. Qualitative phytochemical analysis and GC-MS analysis were conducted for identification of constituents. NAT extracts suppressed arthritic scoring, paw edema, infiltration of inflammatory cells, pannus formation, and bone erosion. The plant extracts ameliorated total leukocytes and platelet counts and nearly normalized red blood cells (RBC) counts and hemoglobin (Hb) content. The extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels. Comparative analysis showed that ethyl acetate extract produced the highest inhibition of paw edema. The major constituents found in ethyl acetate extract can be classified into three major classes, that is, terpenes, terpenoids, fatty acids, and iridoid glycosides. Current study showed that Nyctanthes arbor-tristis ameliorated experimental rheumatoid arthritis and ethyl acetate extract possessed the highest inhibitory activity. PMID:28676830

  10. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis.

    Science.gov (United States)

    Rosmorduc, O; Wendum, D; Corpechot, C; Galy, B; Sebbagh, N; Raleigh, J; Housset, C; Poupon, R

    1999-10-01

    We tested the potential role of vascular endothelial growth factor (VEGF) and of fibroblast growth factor-2 (FGF-2) in the angiogenesis associated with experimental liver fibrogenesis induced by common bile duct ligation in Sprague-Dawley rats. In normal rats, VEGF and FGF-2 immunoreactivities were restricted to less than 3% of hepatocytes. One week after bile duct ligation, hypoxia was demonstrated by the immunodetection of pimonidazole adducts unevenly distributed throughout the lobule. After 2 weeks, hypoxia and VEGF expression were detected in >95% of hepatocytes and coexisted with an increase in periportal vascular endothelial cell proliferation, as ascertained by Ki67 immunolabeling. Subsequently, at 3 weeks the density of von Willebrand-labeled vascular section in fibrotic areas significantly increased. Semiquantitative reverse transcription polymerase chain reaction showed that VEGF(120) and VEGF(164) transcripts, that correspond to secreted isoforms, increased within 2 weeks, while VEGF(188) transcripts remained unchanged. FGF-2 mainly consisting of a 22-kd isoform, according to Western blot, was identified by immunohistochemistry in 49% and 100% of hepatocytes at 3 and 7 weeks, respectively. Our data provide evidence that in biliary-type liver fibrogenesis, angiogenesis is stimulated primarily by VEGF in response to hepatocellular hypoxia while FGF-2 likely contributes to the maintenance of angiogenesis at later stages.

  11. Pharmacological modification of multi-drug resistance (MDR) in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin A and verapamil on MDR leukemia T-cells.

    Science.gov (United States)

    Larsson, R; Nygren, P

    1990-07-15

    A novel fluorometric microculture cytotoxicity assay (FMCA), based on measurements of fluorescein diacetate (FDA) hydrolysis and DNA staining by Hoechst 33342, was used for drug sensitivity testing and detection of resistance reversal in acute lymphoblastic leukemia (ALL) cell lines. The 72-hr assay was found to be sensitive, reproducible and linearly related to the number of viable cells within a broad range of cell concentrations. At clinically achievable drug concentrations, the calcium channel blocker Verapamil (ver) and the immunosuppressant Cyclosporin A (csA) were found to partly reverse acquired Vincristine (vcr) resistance in multi-drug resistant (MDR) T-ALL L100 cells with little or no effect on the drug-sensitive parental L0 cell line. By combining the fluorometric indices, we found that low concentrations of csA were growth-inhibitory, whereas higher concentrations (greater than 10 micrograms/ml) were progressively cytotoxic for drug-sensitive L0 cells. In MDR L100 cells, on the other hand, csA produced significant cell kill even at low drug concentrations. Ver had no effects on sensitive L0 cells but showed considerable cytotoxic action towards MDR L100 cells. There was no apparent relationship between drug reversal of vcr resistance and the cytotoxic actions of the drug per se since the calcium channel blocker diltiazem (dil) significantly potentiated the actions of vcr on MDR L100 cells without being more toxic to these cells (compared to vcr-sensitive L0 cells).

  12. Pulmonary emphysema induced by methylphenidate: experimental study.

    Science.gov (United States)

    Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

    2015-01-01

    Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P pulmonary emphysema.

  13. Boron-implantation-induced crystalline-to-amorphous transition in nickel: An experimental assessment of the generalized Lindemann melting criterion

    International Nuclear Information System (INIS)

    Liu, P.C.; Okamoto, P.R.; Zaluzec, N.J.; Meshii, M.

    1999-01-01

    The generalized Lindemann melting hypothesis has recently been used to develop a unified thermodynamic criterion for melting applicable to both heat-induced melting and disorder-induced crystalline-to-amorphous (c-a) transformation. The hypothesis stipulates that the sum left-angle μ 2 right-angle Total of the static and dynamic root-mean-square (rms) atomic displacements is a constant fraction of the nearest-neighbor distance along the melting curve of a solid. To test this hypothesis, energy-filtered selected area electron-diffraction intensity measurements were used to determine the generalized Lindemann parameter δ=√ (left-angle μ 2 right-angle Total ) /d nn , in which d nn represents the nearest-neighbor distance, as a function of boron concentration during implantation of 50-keV ampersand hthinsp;B + into polycrystalline Ni at 77 K. The onset of amorphization was found to occur close to 10 at.ampersand hthinsp;% boron, which is in good agreement with the value predicted by T o curve calculated using the generalized Lindemann hypothesis. Moreover, the critical value of the generalized Lindemann parameter for amorphization, δ Critical =0.115±0.01, is within experimental error, identical to that for Ni just below its thermodynamic melting temperature of T=1728 ampersand hthinsp;K, hence providing a direct confirmation for the generalized Lindemann melting hypothesis. copyright 1999 The American Physical Society

  14. Experimental and theoretical studies of bombardment induced surface morphology changes

    International Nuclear Information System (INIS)

    Carter, G.; Nobes, M.J.; Williams, J.S.

    1980-01-01

    In this review results of experimental and theoretical studies of solid surface morphology changes due to ion bombardment are discussed. An attempt is undertaken to classify the observed specific features of a structure, generated by ion bombardment [ru

  15. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  16. Experimental evidence of infrared scintillation in crystals

    CERN Document Server

    Belogurov, S; Carugno, Giovanni; Conti, E; Iannuzzi, D; Meneguzzo, Anna Teresa

    2000-01-01

    We present experimental results on infrared emission induced by protons in some solid-state samples. Infrared scintillation occurs in many crystals, with different yield values and time-response behaviours. A rough measurement of the emission wavelength of CsI(Tl) is also reported.

  17. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    Directory of Open Access Journals (Sweden)

    Chloë R McDonald

    2015-09-01

    Full Text Available The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

  18. Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Jumnongprakhon, Pichaya; Sivasinprasasn, Sivanan; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2017-06-01

    Melatonin has been known as a neuroprotective agent for the central nervous system (CNS) and the blood-brain barrier (BBB), which is the primary structure that comes into contact with several neurotoxins including methamphetamine (METH). Previous studies have reported that the activation of melatonin receptors (MT1/2) by melatonin could protect against METH-induced toxicity in brain endothelial cells via several mechanisms. However, its effects on the P-glycoprotein (P-gp) transporter, the active efflux pump involved in cell homeostasis, are still unclear. Thus, this study investigated the role of melatonin and its receptors on the METH-impaired P-gp transporter in primary rat brain microvascular endothelial cells (BMVECs). The results showed that METH impaired the function of the P-gp transporter, significantly decreasing the efflux of Rho123 and P-gp expression, which caused a significant increase in the intracellular accumulation of Rho123, and these responses were reversed by the interaction of melatonin with its receptors. Blockade of the P-gp transporter by verapamil caused oxidative stress, apoptosis, and cell integrity impairment after METH treatment, and these effects could be reversed by melatonin. Our results, together with previous findings, suggest that the interaction of melatonin with its receptors protects against the effects of the METH-impaired P-gp transporter and that the protective role in METH-induced toxicity was at least partially mediated by the regulation of the P-gp transporter. Thus, melatonin and its receptors (MT1/2) are essential for protecting against BBB impairment caused by METH. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Experimental and numerical investigations on flashing-induced instabilities in a single channel

    Energy Technology Data Exchange (ETDEWEB)

    Marcel, Christian P.; Rohde, M.; Van Der Hagen, T.H.J.J. [Department of Physics of Nuclear Reactors, Delft University of Technology (TUDelft), Delft, 2629 JB (Netherlands)

    2009-11-15

    During the start-up phase, natural circulation BWRs (NC-BWRs) need to be operated at low pressure conditions. Such conditions favor flashing-induced instabilities due to the large hydrostatic pressure drop induced by the tall chimney. Moreover, in novel NC-BWR designs the steam separation is performed in the steam separators which create large pressure drops at the chimney outlet, which effect on stability has not been investigated yet. In this work, flashing-induced oscillations occurring in a tall, bottom heated channel are numerically investigated by using a simple linear model with three regions and an accurate implementation for estimating the water properties. The model is used to investigate flashing-induced instabilities in a channel for different values of the core inlet friction value. The results are compared with experiments obtained by using the CIRCUS facility at the same conditions, showing a good agreement. In addition, the experiments on flashing-induced instabilities are presented in a novel manner allowing visualizing new details of the phenomenon numerical stability investigations on the effect of the friction distribution are also done. It is found that by increasing the total restriction in the channel the system is destabilized. In addition, the chimney outlet restriction has a stronger destabilizing effect than the core inlet restriction. A stable two-phase region is observed prior to the instabilities in the experiments and the numerical simulations which may help to pressurize the vessel of NC-BWRs and thus reducing the effects of flashing instabilities during start-up. (author)

  20. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.

    Science.gov (United States)

    Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

    2017-10-01

    Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.

  1. Illusions and delusions: relating experimentally-induced false memories to anomalous experiences and ideas

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    Philip R Corlett

    2009-11-01

    Full Text Available The salience hypothesis of psychosis rests on a simple but profound observation that subtle alterations in the way that we perceive and experience stimuli have important consequences for how important these stimuli become for us, how much they draw our attention, how they embed themselves in our memory and, ultimately, how they shape our beliefs. We put forward the idea that a classical memory illusion – the Deese-Roediger-McDermott (DRM effect – offers a useful way of exploring processes related to such aberrant belief formation. The illusion occurs when, as a consequence of its relationship to previous stimuli, a stimulus is asserted to be remembered even when has not been previously presented. Such illusory familiarity is thought to be generated by the surprising fluency with which the stimulus is processed. In this respect, the illusion relates directly to the salience hypothesis and may share common cognitive underpinnings with aberrations of perception and attribution that are found in psychosis. In this paper, we explore the theoretical importance of this experimentally-induced illusion in relation to the salience model of psychosis. We present data showing that, in healthy volunteers, the illusion relates directly to self reported anomalies of experience and magical thinking. We discuss this finding in terms of the salience hypothesis and of a broader Bayesian framework of perception and cognition which emphasizes the salience both of predictable and unpredictable experiences..

  2. Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

    Science.gov (United States)

    Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

    2017-01-01

    Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

  3. The role of autophagy in cytotoxicity induced by new oncogenic B-Raf inhibitor UI-152 in v-Ha-ras transformed fibroblasts

    International Nuclear Information System (INIS)

    Ahn, Jun-Ho; Ahn, Soon Kil; Lee, Michael

    2012-01-01

    Highlights: ► We recently discovered a potent and selective B-Raf inhibitor, UI-152. ► UI-152 displayed a selective cytotoxicity toward v-Ha-ras transformed cells. ► UI-152-induced growth inhibition was largely meditated by autophagy. ► UI-152 induced paradoxical activation of Raf-1. -- Abstract: In human cancers, B-Raf is the most frequently mutated protein kinase in the MAPK signaling cascade, making it an important therapeutic target. We recently discovered a potent and selective B-Raf inhibitor, UI-152, by using a structure-based drug design strategy. In this study, we examined whether B-Raf inhibition by UI-152 may be an effective therapeutic strategy for eliminating cancer cells transformed with v-Ha-ras (Ras-NIH 3T3). UI-152 displayed selective cytotoxicity toward Ras-NIH 3T3 cells while having little to no effect on non-transformed NIH 3T3 cells. We found that treatment with UI-152 markedly increased autophagy and, to a lesser extent, apoptosis. However, inhibition of autophagy by addition of 3-MA failed to reverse the cytotoxic effects of UI-152 on Ras-NIH 3T3 cells, demonstrating that apoptosis and autophagy can act as cooperative partners to induce growth inhibition in Ras-NIH 3T3 cells treated with UI-152. Most interestingly, cell responses to UI-152 appear to be paradoxical. Here, we showed that although UI-152 inhibited ERK, it induced B-Raf binding to Raf-1 as well as Raf-1 activation. This paradoxical activation of Raf-1 by UI-152 is likely to be coupled with the inhibition of the mTOR pathway, an intracellular signaling pathway involved in autophagy. We also showed for the first time that, in multi-drug resistant cells, the combination of UI-152 with verapamil significantly decreased cell proliferation and increased autophagy. Thus, our findings suggest that the inhibition of autophagy, in combination with UI-152, offers a more effective therapeutic strategy for v-Ha-ras-transformed cells harboring wild-type B-Raf.

  4. Experimental Issues in Testing a Semiactive Technique to Control Earthquake Induced Vibration

    Directory of Open Access Journals (Sweden)

    Nicola Caterino

    2014-01-01

    Full Text Available This work focuses on the issues to deal with when approaching experimental testing of structures equipped with semiactive control (SA systems. It starts from practical experience authors gained in a recent wide campaign on a large scale steel frame structure provided with a control system based on magnetorheological dampers. The latter are special devices able to achieve a wide range of physical behaviours using low-power electrical currents. Experimental activities involving the use of controllable devices require special attention in solving specific aspects that characterize each of the three phases of the SA control loop: acquisition, processing, and command. Most of them are uncommon to any other type of structural testing. This paper emphasizes the importance of the experimental assessment of SA systems and shows how many problematic issues likely to happen in real applications are also present when testing these systems experimentally. This paper highlights several problematic aspects and illustrates how they can be addressed in order to achieve a more realistic evaluation of the effectiveness of SA control solutions. Undesired and unavoidable effects like delays and control malfunction are also remarked. A discussion on the way to reduce their incidence is also offered.

  5. vaccination using profilin and NetB proteins in Montanide IMS adjuvant increases protective immunity against experimentally-induced necrotic enteritis

    Directory of Open Access Journals (Sweden)

    Hyun Soon Lillehoj

    2017-10-01

    Full Text Available Objective The effects of vaccinating 18-day-old chicken embryos with the combination of recombinant Eimeria profilin plus Clostridium perfringens (C. perfringens NetB proteins mixed in the Montanide IMS adjuvant on the chicken immune response to necrotic enteritis (NE were investigated using an Eimeria maxima (E. maxima/C. perfringens co-infection NE disease model that we previously developed. Methods Eighteen-day-old broiler embryos were injected with 100 μL of phosphate-buffered saline, profilin, profilin plus necrotic enteritis B-like (NetB, profilin plus NetB/Montanide adjuvant (IMS 106, and profilin plus Net-B/Montanide adjuvant (IMS 101. After post-hatch birds were challenged with our NE experimental disease model, body weights, intestinal lesions, serum antibody levels to NetB, and proinflammatory cytokine and chemokine mRNA levels in intestinal intraepithelial lymphocytes were measured. Results Chickens in ovo vaccinated with recombinant profilin plus NetB proteins/IMS106 and recombinant profilin plus NetB proteins/IMS101 showed significantly increased body weight gains and reduced gut damages compared with the profilin-only group, respectively. Greater antibody response to NetB toxin were observed in the profilin plus NetB/IMS 106, and profilin plus NetB/IMS 101 groups compared with the other three vaccine/adjuvant groups. Finally, diminished levels of transcripts encoding for proinflammatory cytokines such as lipopolysaccharide-induced tumor necrosis factor-α factor, tumor necrosis factor superfamily 15, and interleukin-8 were observed in the intestinal lymphocytes of chickens in ovo injected with profilin plus NetB toxin in combination with IMS 106, and profilin plus NetB toxin in combination with IMS 101 compared with profilin protein alone bird. Conclusion These results suggest that the Montanide IMS adjuvants potentiate host immunity to experimentally-induced avian NE when administered in ovo in conjunction with the profilin and

  6. The mechanisms of the hadron-nucleus collision processes and of the hadron-nucleus collision induced nuclear reactions - in the light of experimental data

    International Nuclear Information System (INIS)

    Strugalski, Z.; Strugalska-Gola, E.

    1997-01-01

    The mechanisms of the hadron-nucleus collision processes and of the hadron-nucleus collision induced nuclear reactions are described - as experimentally based. The target nuclei are damaged definitely and locally in the collisions and the configurations of the nucleons in them became instable. The configuration must transit into stable stages of the nuclear transition reaction products. The difference between the initial internal energy of the unstable residual nucleus and the total final energy of the stable products of the nuclear transition reaction may be released in some cases

  7. Filament-induced remote surface ablation for long range laser-induced breakdown spectroscopy operation

    International Nuclear Information System (INIS)

    Rohwetter, Ph.; Stelmaszczyk, K.; Woeste, L.; Ackermann, R.; Mejean, G.; Salmon, E.; Kasparian, J.; Yu, J.; Wolf, J.-P.

    2005-01-01

    We demonstrate laser induced ablation and plasma line emission from a metallic target at distances up to 180 m from the laser, using filaments (self-guided propagation structures ∼ 100 μm in diameter and ∼ 5 x 10 13 W/cm 2 in intensity) appearing as femtosecond and terawatt laser pulses propagating in air. The remarkable property of filaments to propagate over a long distance independently of the diffraction limit opens the frontier to long range operation of the laser-induced breakdown spectroscopy technique. We call this special configuration of remote laser-induced breakdown spectroscopy 'remote filament-induced breakdown spectroscopy'. Our results show main features of filament-induced ablation on the surface of a metallic sample and associated plasma emission. Our experimental data allow us to estimate requirements for the detection system needed for kilometer-range remote filament-induced breakdown spectroscopy experiment

  8. Effects of subanesthetic doses of ketamine in cats with induced experimental endotoxemia

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    Felipe Hertzing Farias

    2015-12-01

    Full Text Available ABSTRACT. Farias F.H., Gehrcke M.I., Padilha V.S., Volpato J., Tochetto R., Comassetto F. & Oleskovicz N. [Effects of subanesthetic doses of ketamine in cats with induced experimental endotoxemia.] Efeitos da cetamina em doses subanestésicas em gatos submetidos à endotoxemia experimental. Revista Brasileira de Medicina Veterinária, 37(4:297-302, 2015. Programa de Pós-Graduação em Ciência Animal, Centro de Ciências Agroveterinárias, Universidade do Estado de Santa Catarina, Avenida Luís de Camões, 2090, Bairro Conta Dinheiro, Lages, SC 88520-000, Brasil. E-mail: noleskovicz@yahoo.com.br The clinical endotoxemia is difficult to diagnosis and treatment because of the involvement of multiple organs. This study aimed to evaluate the clinical effects of subanesthetic doses of ketamine, before or after the induction of endotoxemia in cats. Were used nine healthy cats, with 4.3±0.59 kg, autocontroles, placed into three groups: lipopolysaccharide (LPS, n=9 received a bolus of NaCl 0,9 % followed by a continuous infusion (CI of LPS for two hours and; bolus of NaCl 0,9 % followed by CI of LPS for two hours; ketamine/LPS (C/ LPS, n=9 received a bolus of ketamine followed by ketamine CI and LPS for two hours and, after, bolus of saline followed by CI of LPS for another two hours; LPS/ketamine (LPS/C, n=9 received bolus of saline followed by a CI LPS for two hours and then after bolus of ketamine followed by the same CI associated with LPS for two hours. The heart rate was higher for 5 to 120 minutes after initiation of the CI LPS in C/LPS and less than 150 to 240 minutes and from 600 to 720 minutes in LPS compared to the other groups. Five minutes after CI LPS initiation in C/LPS, 60 minutes in LPS/C and 90 minutes to 720 minutes in LPS, FC was higher than at baseline. The PAS was lower in all groups from 360 to 720 minutes compared to baseline. All treatments showed increased TR from 60 to 600 minutes compared to baseline. The levels of glucose

  9. Muon-induced fission

    International Nuclear Information System (INIS)

    Polikanov, S.

    1980-01-01

    A review of recent experimental results on negative-muon-induced fission, both of 238 U and 232 Th, is given. Some conclusions drawn by the author are concerned with muonic atoms of fission fragments and muonic atoms of the shape isomer of 238 U. (author)

  10. HIF-2α-induced chemokines stimulate motility of fibroblast-like synoviocytes and chondrocytes into the cartilage-pannus interface in experimental rheumatoid arthritis mouse models.

    Science.gov (United States)

    Huh, Yun Hyun; Lee, Gyuseok; Lee, Keun-Bae; Koh, Jeong-Tae; Chun, Jang-Soo; Ryu, Je-Hwang

    2015-10-29

    Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2α-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-α transgenic mice were used as experimental RA models. Expression patterns of HIF-2α and chemokines were determined via immunostaining, Western blotting and RT-PCR. FLS motility was evaluated using transwell migration and invasion assays. The specific role of HIF-2α was determined via local deletion of HIF-2α in joint tissues or using conditional knockout (KO) mice. Cartilage destruction, synovitis and pannus formation were assessed via histological analysis. HIF-2α and various chemokines were markedly upregulated in degenerating cartilage and pannus of RA joints. HIF-2α induced chemokine expression by chondrocytes in both primary culture and cartilage tissue. HIF-2α -induced chemokines by chondrocytes regulated the migration and invasion of FLS. Local deletion of HIF-2α in joint tissues inhibited pannus formation adjacent to cartilage tissue and cartilage destruction caused by K/BxN serum transfer. Furthermore, conditional knockout of HIF-2α in cartilage blocked pannus formation in adjacent cartilage but not bone tissue, along with inhibition of cartilage erosion caused by K/BxN serum transfer. Our findings suggest that chemokines induced by IL-1β or HIF-2α in chondrocytes regulate pannus expansion by stimulating FLS migration and invasion, leading to cartilage erosion during RA pathogenesis.

  11. Recent mouse and rat methods for the study of experimental oral candidiasis.

    Science.gov (United States)

    Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

    2013-07-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

  12. Recent mouse and rat methods for the study of experimental oral candidiasis

    Science.gov (United States)

    Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

    2013-01-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

  13. Electrophysiological, vasoactive, and gastromodulatory effects of stevia in healthy Wistar rats.

    Science.gov (United States)

    Yesmine, Saquiba; Connolly, Kylie; Hill, Nicholas; Coulson, Fiona R; Fenning, Andrew S

    2013-07-01

    Antihypertensive and antidiabetic effects of stevia, Stevia rebaudiana (Asteraceae), have been demonstrated in several human and animal models. The current study aims to define stevia's role in modifying the electrophysiological and mechanical properties of cardiomyocytes, blood vessels, and gastrointestinal smooth muscle. Tissues from thoracic aorta, mesenteric arteries, ileum, and left ventricular papillary muscles were excised from 8-week-old healthy Wistar rats. The effects of stevia (1 × 10-9 M to 1 × 10-4 M) were measured on these tissues. Stevia's effects in the presence of verapamil, 4-AP, and L-NAME were also assessed. In cardiomyocytes, stevia attenuated the force of contraction, decreased the average peak amplitude, and shortened the repolarisation phase of action potential - repolarisation phase of action potential20 by 25 %, repolarisation phase of action potential50 by 34 %, and repolarisation phase of action potential90 by 36 %. Stevia caused relaxation of aortic tissues which was significantly potentiated in the presence of verapamil. In mesenteric arteries, incubation with L-NAME failed to block stevia-induced relaxation indicating the mechanism of action may not be fully via nitric oxide-dependent pathways. Stevia concentration-dependently reduced electrical field stimulated and carbachol-induced contractions in the isolated ileum. This study is the first to show the effectiveness of stevia in reducing cardiac action potential duration at 20 %, 50 %, and 90 % of repolarisation. Stevia also showed beneficial modulatory effects on cardiovascular and gastrointestinal tissues via calcium channel antagonism, activation of the M2 muscarinic receptor function, and enhanced nitric oxide release. Georg Thieme Verlag KG Stuttgart · New York.

  14. Surgical manipulation compromises leukocyte mobilisation responses and inflammation after experimental cerebral ischaemia in mice

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    Adam eDenes

    2014-01-01

    Full Text Available Acute brain injury results in peripheral inflammatory changes, although the impact of these processes on neuronal death and neuroinflammation is currently unclear. To facilitate the translation of experimental studies to clinical benefit, it is vital to characterize the mechanisms by which acute brain injury induces peripheral inflammatory changes, and how these are affected by surgical manipulation in experimental models. Here we show that in mice, even mild surgical manipulation of extracranial tissues induced marked granulocyte mobilisation (300% and systemic induction of cytokines. However, intracranial changes induced by craniotomy, or subsequent induction of focal cerebral ischaemia were required to induce egress of CXCR2-positive granulocytes from the bone marrow. CXCR2 blockade resulted in reduced mobilisation of granulocytes from the bone marrow, caused an unexpected increase in circulating granulocytes, but failed to effect brain injury induced by cerebral ischaemia. We also demonstrate that isoflurane anaesthesia interferes with circulating leukocyte responses, which could contribute to the reported vascular and neuroprotective effects of isoflurane. In addition, no immunosuppression develops in the bone marrow after experimental stroke. Thus, experimental models of cerebral ischaemia are compromised by surgery and anaesthesia in proportion to the severity of surgical stress and overall tissue injury. Understanding the inherent confounding effects of surgical manipulation and development of new models of cerebral ischaemia with minimal surgical intervention could facilitate better understanding of interactions between inflammation and brain injury.

  15. Friction-induced Vibrations in an Experimental Drill-string System for Various Friction Situations

    NARCIS (Netherlands)

    Mihajlovic, N.; Wouw, van de N.; Hendriks, M.P.M.; Nijmeijer, H.

    2005-01-01

    Friction-induced limit cycling deteriorates system performance in a wide variety of mechanical systems. In this paper, we study the way in which essential friction characteristics affect the occurrence and nature of friction-induced limit cycling in flexible rotor systems. This study is performed on

  16. MRP-1 and BCRP Promote the Externalization of Phosphatidylserine in Oxalate-treated Renal Epithelial Cells: Implications for Calcium Oxalate Urolithiasis.

    Science.gov (United States)

    Li, YiFu; Yu, ShiLiang; Gan, XiuGuo; Zhang, Ze; Wang, Yan; Wang, YingWei; An, RuiHua

    2017-09-01

    To investigate the possible involvement of multidrug resistance-associated protein 1 (MRP-1) and breast cancer resistance protein (BCRP) in the oxalate-induced redistribution of phosphatidylserine (PS) in renal epithelial cell membranes. A western blot analysis was used to examine the MRP-1 and BCRP expression levels. Surface-expressed PS was detected by the annexin V-binding assay. The cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate was used to measure the intracellular reactive oxygen species (ROS) level. A rat model of hyperoxaluria was obtained using 0.5% ethylene glycol and 1.0% ammonium chloride. In addition, certain animals received verapamil (50 mg/kg body weight), which is a common inhibitor of MRP-1 and BCRP. The degree of nephrolithiasis was assessed histomorphometrically using sections stained by Pizzolato method and by measuring the calcium oxalate crystal content in the renal tissue. Oxalate produced a concentration-dependent increase in the synthesis of MRP-1 and BCRP. Treatment with MK571 and Ko143 (MRP-1- and BCRP-specific inhibitors, respectively) significantly attenuated the oxalate-induced PS externalization. Adding the antioxidant N-acetyl-l-cysteine significantly reduced MRP-1 and BCRP expression. In vivo, markedly decreased nephrocalcinosis was observed compared with that in the rat model of hyperoxaluria without verapamil treatment. Oxalate induces the upregulation of MRP-1 and BCRP, which act as phospholipid floppases causing PS externalization in the renal epithelial cell membrane. The process is mediated by intracellular ROS production. The ROS-mediated increase in the synthesis of MRP-1 and BCRP can play an important role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A mechanistic evaluation of the traditional uses of Nepeta ruderalis in gastrointestinal and airway disorders.

    Science.gov (United States)

    Mahmood, Hassan; Chaudhry, Mueen Ahmad; Masood, Zeeshan; Saeed, Muhammad Asad; Adnan, Sherjeel

    2017-12-01

    Nepeta ruderalis Buch.-Ham. (Lamiaceae), locally known as Badranj Boya, is an aromatic herb used traditionally as an antispasmodic, antidiarrhoeal, and anti-asthamatic remedy. Aqueous methanolic extract of N. ruderalis was studied to investigate its traditional uses. Study was conducted from September 2015 to February 2016. In vitro spasmolytic and broncho-relaxant activity of crude extract of N. ruderalis (whole plant) was evaluated at 0.01-10 mg/mL final bath concentration in isolated rabbit jejunum and tracheal tissues, using PowerLab data acquisition system (Transonic Systems Inc., Ithaca, NY). In vivo antidiarrhoeal activity was evaluated in castor oil-induced diarrhoeal mice at the dose of 300 and 500 mg of crude extract orally. Crude extract of N. ruderalis completely relaxed spontaneously contracting, high K + (80 mM) and carbachol (1 μM) induced contracted jejunum with an EC 50 value of 5.85 (5.45-6.27), 4.0 (3.80-4.23) and 2.86 (2.48-3.29), similar to verapamil. Nr.Cr relaxed high K + and carbachol induced contractions, at 5 and 10 mg/mL with an EC 50 value of 2.37 (2.11-2.67) and 3.26 (2.9-3.67), respectively, and also displaced calcium concentration-response curves toward right at 0.1 and 0.3 mg/mL. Nr.Cr exhibited antidiarrhoeal protection at a dose of 300 and 500 mg/kg, similar to verapamil, whereas no acute toxicity signs were seen up to 5 g/kg in healthy mice. Results suggest the presence of spasmolytic and broncho-relaxant effects in the crude extract of N. ruderalis, possibly mediated through calcium channel-blocking activity, providing the pharmacological basis for its traditional uses in gastrointestinal and airway disorders.

  18. Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-03-01

    The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. Extension of the energy range of the experimental activation cross-sections data of longer-lived products of proton induced nuclear reactions on dysprosium up to 65MeV.

    Science.gov (United States)

    Tárkányi, F; Ditrói, F; Takács, S; Hermanne, A; Ignatyuk, A V

    2015-04-01

    Activation cross-sections data of longer-lived products of proton induced nuclear reactions on dysprosium were extended up to 65MeV by using stacked foil irradiation and gamma spectrometry experimental methods. Experimental cross-sections data for the formation of the radionuclides (159)Dy, (157)Dy, (155)Dy, (161)Tb, (160)Tb, (156)Tb, (155)Tb, (154m2)Tb, (154m1)Tb, (154g)Tb, (153)Tb, (152)Tb and (151)Tb are reported in the 36-65MeV energy range, and compared with an old dataset from 1964. The experimental data were also compared with the results of cross section calculations of the ALICE and EMPIRE nuclear model codes and of the TALYS nuclear reaction model code as listed in the latest on-line libraries TENDL 2013. Copyright © 2015. Published by Elsevier Ltd.

  20. Experimental demonstration of a parasite-induced immune response in wild birds: Darwin's finches and introduced nest flies.

    Science.gov (United States)

    Koop, Jennifer A H; Owen, Jeb P; Knutie, Sarah A; Aguilar, Maria A; Clayton, Dale H

    2013-08-01

    Ecological immunology aims to explain variation among hosts in the strength and efficacy of immunological defenses. However, a shortcoming has been the failure to link host immune responses to actual parasites under natural conditions. Here, we present one of the first experimental demonstrations of a parasite-induced immune response in a wild bird population. The recently introduced ectoparasitic nest fly Philornis downsi severely impacts the fitness of Darwin's finches and other land birds in the Galápagos Islands. An earlier study showed that female medium ground finches (Geospiza fortis) had P. downsi-binding antibodies correlating with presumed variation in fly exposure over time. In the current study, we experimentally manipulated fly abundance to test whether the fly does, in fact, cause changes in antibody levels. We manipulated P. downsi abundance in nests and quantified P. downsi-binding antibody levels of medium ground finch mothers, fathers, and nestlings. We also quantified host behaviors, such as preening, which can integrate with antibody-mediated defenses against ectoparasites. Philornis downsi-binding antibody levels were significantly higher among mothers at parasitized nests, compared to mothers at (fumigated) nonparasitized nests. Mothers with higher antibody levels tended to have fewer parasites in their nests, suggesting that antibodies play a role in defense against parasites. Mothers showed no behavioral changes that would enhance the effectiveness of the immune response. Neither adult males, nor nestlings, had P. downsi-induced immunological or behavioral responses that would enhance defense against flies. None of the parasitized nests fledged any offspring, despite the immune response by mothers. Thus, this study shows that, while the immune response of mothers appeared to be defensive, it was not sufficient to rescue current reproductive fitness. This study further shows the importance of testing the fitness consequences of immune