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Sample records for experimental verapamil induced

  1. Verapamil induced ventricular hypertrophy in conscious dogs.

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    French, W J; Garner, D; Adomian, G E; Averill, W; Laks, M M

    1989-08-01

    Verapamil is used clinically in the treatment of various cardiac diseases including hypertrophic cardiomyopathy. Its long term effects on ventricular mass are not well known. In 11 conscious dogs heart rate, aortic and left ventricular pressures, cardiac output, a methoxamine induced stress ventricular function test and left ventriculography were performed. These variables were measured prior to and following a mean 7.2 month infusion of verapamil at 0.005 or 0.01 mg.kg-1.min-1 using a subcutaneously implanted pump. Resting haemodynamic variables and left ventricular ejection fraction [60(SD 6) v 55(6)%] were unchanged between baseline and chronic verapamil studies, but the slope of the methoxamine induced stress ventricular function test decreased from 3.9(0.8) to 2.1 (1.3). After verapamil was discontinued the mean slope of the stress ventricular function test returned to the baseline 4.0(1.7). Total ventricular weight increased 22% from 176.1(17.5) g.m-2 in controls to 215.6(29.5) g.m-2 (p less than 0.01) in the verapamil animals. The right ventricular weight increased 25% from 46(5.9) to 57.6(9.1) g.m-2 (p less than 0.01); the septum weight increased 26% from 42.5(4.1) to 53.7(7.2) g.m-2 (p less than 0.001); and the left ventricular free wall weight increased 19% from 87.4(9.8) to 103.9(15.7) g.m-2 (p less than 0.01). The increase in ventricular weights was not due to fibrosis or oedema since hydroxyproline contents and wet/dry ratios were not increased. In conclusion, a chronic infusion of verapamil in conscious dogs caused no change in resting haemodynamic variables but produced reversible depression of stress ventricular function and biventricular and septal hypertrophy.

  2. Neuroprotective effect of chronic verapamil treatment on cognitive and noncognitive deficits in an experimental Alzheimer's disease in rats.

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    Popović, M; Caballero-Bleda, M; Popović, N; Bokonjić, D; Dobrić, S

    1997-11-01

    It is well known that disturbance of calcium homeostasis has a significant role in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). Our recent data suggest that acute treatment with the calcium antagonist verapamil can improve some behavioral deficits in an experimental model of AD. Therefore, the present study was done to establish the effect of chronically administered verapamil on cognitive and noncognitive behavior of rats with bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an animal model of AD. The NBM lesions produce a deficit in performance of diverse behavior tests: active avoidance (AA), low level of fear (the open field test) as well as aggressive (the test of foot-shock induced aggression) and depressive (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of NBM and then repeatedly administered during the next 8 days (twice a day). Performance of the two-way active avoidance test, the open field test, the foot shock-induced aggression test and the learned helplessness test were done on day 4 after the last verapamil or saline treatment (day 13 after the lesion). Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in the performance of AA, the open field behavior, and the depression, but not the aggressive behavior. The obtained beneficial effect of chronic administered verapamil suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a reasonable way to prevent the behavioral deficits in an experimental model of AD.

  3. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain.

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    Tamaddonfard, Esmaeal; Erfanparast, Amir; Taati, Mina; Dabbaghi, Milad

    2014-01-01

    Calcium, through its various channels involves in local, spinal and supra-spinal transmission of pain. In the present study, we investigated the separate and combined treatment effects of verapamil (a calcium channel blocker), morphine (an opioid agonist) and naloxone (an opioid antagonist) on pain in the orofacial region of rats. Orofacial pain was induced by subcutaneous (SC) injection of formalin (50 µL, 1.5%) into the left upper lip side, and the time durations spent face rubbing with epsilateral forepaw were recorded in three min blocks for a period of 45 min. Formalin induced a biphasic pattern (first phase: 0-3 min; second phase: 15-33 min) of pain. Intraperitoneal (IP) injections of verapamil (2 and 8 mg kg(-1)) and morphine (2 and 4 mg kg(-1)) suppressed orofacial pain. Co-administration of sub-analgesic doses of verapamil (0.5 mg kg(-1)) and morphine (1 mg kg(-1)) produced second phase analgesia. Both phases of formalin-induced pain were suppressed when an analgesic dose (2 mg kg(-1)) of verapamil co-administered with a sub-analgesic dose (1 mg kg(-1)) of morphine. The SC injection of naloxone (2 mg kg(-1)) alone with no effect on pain intensity, prevented the antinociceptive effects induced by morphine (2 mg kg(-1)), but not verapamil (2 mg kg(-1)). The obtained results showed antinociceptive effects for verapamli and morphine on orofacial pain. Co-administrations of verapamil and morphine produced antinociceptive effects. It seems that opioid analgesic system may not have a role in the verapamil-induced antinociception.

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

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    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

  5. The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig.

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    Grant, A O; Katzung, B G

    1976-02-01

    The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.

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

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

    1988-12-01

    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 /sup 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 /sup 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.

  7. Effect of Verapamil on the formation of adhesions in aseptic peritonitis

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    Sergey V. Skalskiy

    2017-01-01

    Full Text Available Objective. An experimental study of verapamil new properties, such as the regulation of the connective tissue formation.Materials and мethods. The study was conducted in an aseptic inflammation of the peritoneum both on the body and cell culture in simulating haemoperitoneum in rats. The optimal dose (0,1 mg/kg body weight for intraperitoneal verapamil administration was fixed, which did not provoke significant and reliable changes in cardio- and hemodynamics.Results. It was revealed that verapamil injected intraperitoneally at a dose of 0,1 mg/kg demonstrates a pronounced pharmacological effect against excessive production of the connective tissue in hemoperitoneum. Conclusion. It was proved (in vivo and in vitro the possibility of drug-induced modulating of the proliferative drug and collagen-producing fibroblast functions by regulating the calcium metabolism in these cells with verapamil.

  8. A randomised controlled trial evaluating renal protective effects of selenium with vitamins A, C, E, verapamil, and losartan against extracorporeal shockwave lithotripsy-induced renal injury.

    Science.gov (United States)

    El-Nahas, Ahmed R; Elsaadany, Mohamed M; Taha, Diaa-Eldin; Elshal, Ahmed M; El-Ghar, Mohamed Abo; Ismail, Amani M; Elsawy, Essam A; Saleh, Hazem H; Wafa, Ehab W; Awadalla, Amira; Barakat, Tamer S; Sheir, Khaled Z

    2017-01-01

    To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)-induced renal injury. A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week (P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL (P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post-ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post-ESWL renal obstruction. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  9. Effects of verapamil, carbenoxolone and N-acetylcysteine on gastric wall mucus and ulceration in stressed rats.

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    Koo, M W; Ogle, C W; Cho, C H

    1986-01-01

    The effects of verapamil on gastric wall mucus and ulceration were studied in rats which were restrained and exposed to 4 degrees C (stress). Stress for 2 h significantly depleted stomach wall mucus and produced marked gastric glandular ulcers. Verapamil pretreatment (2, 4, 8 or 16 mg/kg), injected intraperitoneally 30 min before experimentation, significantly prevented stress-induced mucus depletion and gastric ulceration; however, it did not itself influence stomach wall mucus levels in nonstressed animals. Intragastric administration of carbenoxolone (100 or 200 mg/kg), also given 30 min before stress, exhibited similar actions as verapamil. A 15% solution of N-acetylcysteine (10 ml/kg), given orally, strongly decreased the mucus content in both nonstress and stress conditions; it induced ulcers in nonstressed rats, and worsened stress ulceration. These effects were not reversed by verapamil pretreatment. The influence of multiple-dose pretreatment with verapamil or carbenoxolone on mucus content and ulceration in the gastric glandular mucosa during stress is also discussed. It is concluded that gastric wall mucus depletion is likely to play an important role in stress ulcer formation; the antiulcer action of verapamil could partly be due to the preservation of mucus.

  10. Verapamil inhibits the glucose transport activity of GLUT1.

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    Louters, Larry L; Stehouwer, Nathan; Rekman, Janelle; Tidball, Andrew; Cok, Alexandra; Holstege, Christopher P

    2010-06-01

    Calcium channel blocker toxicity has been associated with marked hyperglycemia responsive only to high-dose insulin therapy. The exact mechanism(s) of this induced hyperglycemia has not been clearly delineated. The glucose transporter GLUT1 is expressed in a wide variety of cell types and is largely responsible for a basal level of glucose transport. GLUT1 also is activated by cell stress. The specific purpose of this study was to investigate the effects of the calcium channel blocker verapamil on the glucose uptake activity of GLUT1 in L929 fibroblasts cells. Dose-dependent effects of verapamil on glucose uptake were studied using L929 fibroblast cells with 2-deoxyglucose. Verapamil had a dose-dependent inhibitory effect on both basal and stress-activated transport activity of GLUT1. Basal activity was inhibited 50% by 300 μM verapamil, while 150 μM verapamil completely inhibited the activation induced by the stress of glucose deprivation. These effects were reversible and required verapamil to be present during the stress. Alteration of calcium concentrations by addition of 5 mM CaCl₂ or 4 mM EDTA had no effect on verapamil action. This study reveals the unique finding that verapamil has inhibitory effects on the transport activity of GLUT1 independent of its effects on calcium concentrations. The inhibition of GLUT1 may be one of the contributing factors to the hyperglycemia observed in CCB poisoning.

  11. 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.

  12. (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

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    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.

  13. Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.

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    Chauffert, B.; Rey, D.; Coudert, B.; Dumas, M.; Martin, F.

    1987-01-01

    We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as efficient as its precursor. Optimal concentrations of amiodarone are obtained without side effects in the sera of patients treated by oral administration followed by a loading infusion of amiodarone. On the other hand, maximal tolerated levels of verapamil reported in clinical trials are less efficient than amiodarone maximal levels in the reversal of resistance to anthracyclines in our experimental model in vitro. We suggest that amiodarone, which is more efficient and less toxic than verapamil, could be substituted for verapamil in future clinical trials. PMID:3663463

  14. Hemicrania continua responsive to verapamil.

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    Rajabally, Yusuf A; Jacob, Saiju

    2005-09-01

    Hemicrania continua (HC) is a rare headache syndrome, typically responsive to indomethacin, although patients resistant to this drug have been described. Few treatment alternatives have been proposed in the literature. We here report a patient with HC whose initial excellent response to indomethacin faded but then responded remarkably to verapamil.

  15. Influence of nimodipine, verapamil and lanthanum on histamine release from human basophils

    DEFF Research Database (Denmark)

    Jensen, C B; Thastrup, Ole; Norn, S

    1987-01-01

    and the calcium channels, using the calcium antagonists nimodipine, verapamil and lanthanum. Anti-IgE-induced histamine release was inhibited by verapamil, nimodipine and lanthanum. When cells were pretreated with sialidase in order to remove sialic acid from the cell membrane, the inhibitory action of nimodipine...... was abolished, whereas the inhibition by verapamil or lanthanum was unaffected. This difference may be explained by the different mode of action of the calcium channel antagonists, and the results suggest an association between membrane sialic acid and the calcium channel....

  16. Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.

    OpenAIRE

    Chauffert, B.; D. Rey; Coudert, B; Dumas, M.; F Martin

    1987-01-01

    We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as...

  17. Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats

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    Verónica Giménez De Béjar

    2017-08-01

    Full Text Available Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p. as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg. In conclusion, the present data suggest that (1 the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2 verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3 exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory.

  18. Verapamil

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    ... other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart ... Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat ...

  19. Circadian variation in the pharmacokinetics of verapamil

    DEFF Research Database (Denmark)

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

    1989-01-01

    Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h. No major difference in exercise parameters was found. During the evening dosage schedule a significantly...... 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...

  20. Methoxyflurane anesthesia augments the chronotropic and dromotropic effects of verapamil.

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    Jamali, F; Mayo, P R

    1999-01-01

    Inhalation anesthetics have been shown to have electrical suppressant effects on excitable membranes such as the cardiac conduction system. Therefore, the anesthetized patient or laboratory animal may respond differently to cardiac drugs when compared with their conscious counterparts. The purpose of this study was to assess the effects of anesthesia with methoxyflurane (MF) on the dromotropic and chronotropic effects of verapamil (VER) in the rat. A lead I ECG was measured using subcutaneous electrodes placed both axilli and over the xyphoid process in male Sprague-Dawley rats. Dromotropic effect was measured using the PR-interval which indicated the electrical spread across the atria to the AV-node and chronotropic effects were determined using RR-interval. A total of six animals were randomized to receive 10 mg/kg s.c. of verapamil in the presence or absence of general anesthesia containing methoxyflurane. In addition, PR-interval and RR-intervals were determined in the presence of only methoxyflurane and at rest without any drug exposure. The time for the ECG to normalize after exposure to methoxyflurane and/or verapamil was also determined. Exposure to verapamil alone resulted in a 5% prolongation in PR-interval and 6% prolongation in RR-interval. Methoxyflurane alone had a larger effect than verapamil demonstrating a 14.5% prolongation in PR-interval and a 12.3% in RR-interval which was statistically significant. The combination of MF + VER resulted in a synergistic prolongation in PR-interval to 28. 7% while the effect on RR-interval was additive with an increase to 17.6%. The time for the ECG to normalize after exposure to VER, MF and VER + MF was 37.5 15.1 min, 69.8 5.3 min, and 148.5 +/- 6.6 min respectively. General anesthesia with MF enhances the dromotropic and chronotropic effect of VER. This should be considered when MF-anesthesia is used in experimental procedure.

  1. Study of rat hepatocytes in primary culture submitted to hypoxia and reoxygenation: action of the cytoprotectors prostaglandin E1, superoxide dismutase, allopurinol and verapamil.

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    Andrade Jr, Dahir Ramos de; Andrade, Dahir Ramos de; Santos, Sânia Alves Dos

    2009-01-01

    Exposure of hepatocytes to pathological conditions in a microenvironment of hypoxia and reoxygenation is very frequent in hepatic diseases. Several substances present perspectives for cytoprotective action on hepatocyte submitted to reoxygenation after hypoxia and simple hypoxia. We research therapeutic options for hepatocytes submitted to hypoxia and hypoxia + reoxygenation injury. Primary culture of rat hepatocytes was submitted to hypoxia (2 hours) plus reoxygenation (2 hours) and simple hypoxia (4 hours) in the presence or the absence of cytoprotectors. The hepatocyte lesion was evaluated by functional criteria through percentage of lactate dehydrogenase released and cell viability. The effects of the cytoprotectors prostaglandin E1 3 etag/mL, superoxide dismutase 80 microg/mL, allopurinol 20 microM and verapamil 10-4 M were studied in this model of injury. Reoxygenation after hypoxia induced more significant lesion in cultured hepatocytes compared to simple hypoxia, detected by analysis of functional criteria. There was a significant reduction of percentage of lactate dehydrogenase released and a significant increase of percentage of cell viability in the hypoxia + reoxygenation + cytoprotectors groups compared to hypoxia + reoxygenation groups. Prostaglandin E1, superoxide dismutase and verapamil also protected the group submitted to simple hypoxia, when evaluated by functional criteria. We conclude that reoxygenation after hypoxia significantly increased the lesion of cultured rat hepatocytes when compared to simple hypoxia. Prostaglandin E1, superoxide dismutase, allopurinol and verapamil acted as cytoprotectors to the rat cultured hepatocytes submitted to hypoxia + reoxygenation in vitro. The substances prostaglandin E1, superoxide dismutase and verapamil protected hepatocytes submitted to simple hypoxia on the basis of all the criteria studied in this experimental model.

  2. Synergy between verapamil and other multidrug -resistance ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    dose combinations at equally effective levels, but for assessing synergy or antagonism both the expected effects and the actual effects need to be determined with high precision. Modulators such as verapamil, quinine and others, which reverse the multidrug resistance of cancer cells (Sharom. 1997), bind to membranes in ...

  3. 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.

  4. Calcium and P-glycoprotein independent synergism between schweinfurthins and verapamil.

    Science.gov (United States)

    Sheehy, Ryan M; Kuder, Craig H; Bachman, Zoe; Hohl, Raymond J

    2015-01-01

    Schweinfurthins are intriguing natural products with anti-cancer activities and as yet incompletely understood mechanisms of action. We investigated whether inhibitors of P-glycoprotein (Pgp), in a manner analogous to other natural products, might enhance schweinfurthins' growth inhibitory actions by increasing intracellular schweinfurthin levels. Both the schweinfurthin-sensitive glioblastoma multiforme cell line SF-295 and relatively insensitive lung carcinoma cell line A549 were treated with 2 schweinfurthin analogs: 3-deoxyschweinfurthin B-p-nitro bis-stilbene (3dSB-PNBS) and 5'-methylschweinfurthin G (methyl-G). There was a synergistic enhancement of growth inhibition with the combination of the Pgp inhibitor verapamil and both analogs in SF-295 cells. Methyl-G, verapamil, and the combination did not result in alterations to intracellular calcium concentration. Verapamil increased the intracellular concentration of 3dSB-PNBS in both SF-295 and A549 cells in a Pgp-independent manner. Methyl-G, verapamil, and the combination do not result in increased ER stress. Methyl-G increased the intracellular concentration of a known Pgp substrate, Rhodamine 123 in SF-295 cells. Reduction of cellular cholesterol leads to the accumulation of Pgp substrates, as Pgp requires cholesterol for proper function. Since 3dSB enhances lovastatin-induced upregulation of the cholesterol efflux pump ABCA1, it is intriguing that co-treatment with cholesterol rescued the methyl-G-induced increase in Rhodamine 123 intracellular concentration. These studies support the hypothesis that verapamil potentiates the schweinfurthin growth inhibitory effect by increasing its intracellular concentration.

  5. The effect of verapamil on the cardiotoxic activity of Portuguese man-o'war (Physalia physalis) and sea nettle (Chrysaora quinquecirrha) venoms.

    Science.gov (United States)

    Burnett, J W; Gean, C J; Calton, G J; Warnick, J E

    1985-01-01

    Verapamil, a calcium antagonist, is effective in delaying death in mice after i.v. challenge with sea nettle (Chrysaora quinquecirrha) or Portuguese man-o'war (Physalia physalis) crude venom. Death caused by these venoms could also be delayed by prior medication of the animals. Continuous EKG monitoring of sea nettle venom-challenged rats demonstrated that a single rapid injection of verapamil might require 4 min to be effective and that up to four repeated injections may be necessary to counteract the venom-induced abnormalities. Verapamil reduced the sea nettle venom-induced positive inotropic effect on isolated guinea pig atrial strips. These data further indicate the effectiveness of verapamil as a therapeutic agent against jellyfish cardiotoxins.

  6. [Behaviour of serum CPK curves in acute myocardial infarction treated with digitalis, verapamil and combined verapamil-digitalis (author's transl)].

    Science.gov (United States)

    Vincenzi, M; Allegri, P; Cappelletti, F; Comacchio, G; De Lio, U; Morlino, T; Ometto, R; Zanchetta, M; Maiolino, P

    1981-01-01

    In order to compare the effectiveness of different therapeutic regimens in reducing infarct size serial determinations of CPK activity (at 4 hourly intervals in the first 48 hours from the admission to CCU, at the 72th and at 120th hours) were performed in 100 patients with transmural AMI (53 anterior and 47 inferior) with no obvious evidence of LV failure and basal CPK levels lower than 50 U/L. 20 patients (control group) have been treated with glucose-insulin-potassium (GIK). 20 patients have been treated with GIK plus Verapamil (GIK + V). Verapamil was administered at the dose of 50 mg in continuous drip. 20 patients received GIK plus digoxin at the dose of 0.25 mg b.i.d. (GIK + D). 40 patients received GIK, Verapamil and digoxin at the above doses (GIK + V + D). Different values of CKr and infarct size (IS.) show a statistically significant difference between the various regimens, which is more evident if we consider the whole series. Infarct size was greater in patients treated with digoxin with respect to controls, while it was smaller in patients treated with Verapamil. Combined Verapamil-digoxin therapy is associated to an enzymatic behaviour not different from controls. Authors emphasize that in uncomplicated AMI digoxin causes an increase in infarct size while Verapamil reduces significantly it. Association of Verapamil allows the use of digoxin, if clinically justified, without increase in infarct size.

  7. Experimentally induced Porcine Coccidiosis | Onawunmi | Nigerian ...

    African Journals Online (AJOL)

    Journal Home > Vol 4, No 2 (1977) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Experimentally induced Porcine Coccidiosis. OA Onawunmi. Abstract. No abstract.

  8. EFFECTS OF VERAPAMIL ON CHICKEN BIVENTER - CERVICIS MUSCLE

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. The effect of verapamil and diltiazem on cardiac stimulant effect of adrenaline and calcium chloride on isolated frog heart

    Directory of Open Access Journals (Sweden)

    Lakhavat Sudhakar, Naveen Kumar T, Tadvi NA, Venkata Rao Y

    2013-04-01

    Full Text Available Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus reduce the frequency of opening of these channels in response to depolarization. The result is a marked decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, is cardio selective, nifedipine is vascular smooth muscle selective, while diltiazem exhibits intermediate selectivity. Methods: In the present study, the effect of two Ca++ channel blocker, Verapamil and Diltiazem were compared on the isolated frog heart by using adrenaline & calcium chloride as standard on frog heart contractility. Results and conclusion: Adrenaline and calcium chloride increased the amplitude of contraction of isolated perfused frog heart. The L- type of Ca2+ channel blockers verapamil and diltiazem produced dose dependent (2mg, 4mg, 8mg, and 16mg reduction in the amplitude of contraction produced by calcium chloride in isolated perfused frog heart. There was no statistical significant difference (p > 0.05 between the inhibitory effect of diltiazem and verapamil on calcium chloride induced contraction of isolated frog heart.

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

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    considerably among subjects. The dose of verapamil used for cluster headache is approximately double the dose used in cardiovascular disease, most likely because verapamil is a substrate for the efflux transporter P-glycoprotein in the blood-brain barrier. The access of verapamil to the central nervous system......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...

  12. Bioconcentration of two basic pharmaceuticals, verapamil and clozapine, in fish.

    Science.gov (United States)

    Nallani, Gopinath C; Edziyie, Regina E; Paulos, Peter M; Venables, Barney J; Constantine, Lisa A; Huggett, Duane B

    2016-03-01

    The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 μg/L and 419 μg/L of verapamil (500 μg/L nominal) or 28.5 μg/L and 40 μg/L of clozapine (50 μg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients. © 2016 SETAC.

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

    Science.gov (United States)

    Wu, Gao; Wu, Hanbin

    2014-01-01

    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. PMID:25114705

  14. 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.

  15. Experimental hypocalcemia induced by hemodialysis in goats.

    Science.gov (United States)

    Yamagishi, N; Oishi, A; Sato, J; Sato, R; Naito, Y

    1999-12-01

    To evaluate whether hemodialysis with a dialysate containing no calcium (Ca-free HD) can induce hypocalcemia and restore the clinical signs and blood biochemical changes in naturally occurred hypocalcemic disorder in ruminants, the clinical signs and the changes in plasma electrolytes and minerals concentrations were observed in goats during 6-hr hemodialysis. The four goats received hemodialysis with the dialysate containing calcium (Ca HD), and 10 days later they had Ca-free HD. The plasma ionized Ca (Ca++) and total Ca (TCa) concentrations were not affected by Ca HD, whereas the levels significantly decreased during whole period of Ca-free HD. The Ca++ and TCa concentrations were 0.69+/-0.06 mmol/l and 5.9+/-0.3 mg/dl at 6 hr of Ca-free HD, respectively. The clinical signs observed during Ca-free HD seemed to resemble to those in naturally occurred hypocalcemic cases that were reported previously. Therefore, Ca-free HD was suggested to be one of the possible methods to induce experimental hypocalcemia in ruminants.

  16. Effect of verapamil on ischemia and ventricular arrhythmias after an acute myocardial infarction: prognostic implications. The Danish Verapamil Infarction Trial II Study Group

    DEFF Research Database (Denmark)

    Vaage-Nilsen, M; Rasmussen, Verner; Hansen, J F

    1991-01-01

    This article is a review of presented subsets of the Danish Verapamil Infarction Trial II (DAVIT II) regarding the effect of verapamil on postinfarction ischemia, ventricular arrhythmias, and heart rate (HR), and the prognostic implications of these findings. Patients underwent Holter monitoring......: In the placebo group the prevalence and incidence of many ventricular ectopic beats (VEBs), i.e., more than 10 VEBs/h, increased significantly during the first years after infarction; this was not the case in the verapamil patients group. The mean HR was significantly reduced by verapamil treatment after 1 month...

  17. Effect of verapamil on arrhythmias and heart rate during 16 months following an acute myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction

    DEFF Research Database (Denmark)

    Vaage-Nilsen, M; Rasmussen, Verner; Hansen, J F

    1994-01-01

    The present study was a prospectively planned subset of the postinfarction, double blind, randomized, multicenter, placebo controlled trial of verapamil, DAVIT II. Patients had 24 hours of Holter monitoring before randomization, i.e., second week after infarction (placebo, n = 122; verapamil, n...

  18. Experimental model to induce obesity in rats

    National Research Council Canada - National Science Library

    Vinicius Von Diemen; Eduardo Neubarth Trindade; Manoel Roberto Maciel Trindade

    2006-01-01

    .... Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH...

  19. Diltiazem and verapamil preferentially block inactivated cardiac calcium channels.

    Science.gov (United States)

    Kanaya, S; Arlock, P; Katzung, B G; Hondeghem, L M

    1983-02-01

    Diltiazem has been proposed to act by blocking calcium channels of cardiac and smooth muscle since it has pharmacological [12-14] and clinical [10] effects that resemble those of verapamil, an agent that has been shown to block these channels [3]. However, block of the slow inward current by diltiazem has not been directly demonstrated. In fact, it has been suggested that diltiazem has an entirely different mechanism of action [7]. We therefore studied the blocking effects of diltiazem and verapamil on cardiac calcium channels by measuring the slow inward current in voltage-clamped ferret myocardium. Both drugs blocked the slow inward current in a use-dependent fashion, i.e. the block was enhanced by increased frequency of activating clamps and by more positive holding potentials. However, we found that short single activating clamps resulted in minimal block, whereas prolonging the clamp step progressively enhanced the blockade. Thus, a single long clamp caused as much blockade as a train of shorter pulses. These results demonstrate that diltiazem and verapamil block the slow inward current by binding to calcium channels in a state-dependent fashion, i.e. inactivated channels have a high affinity for the drugs, while rested and open channels have a lower affinity.

  20. Individualizing treatment with verapamil for cluster headache patients.

    Science.gov (United States)

    Blau, Joseph N; Engel, Hans O

    2004-01-01

    Verapamil is currently the best available prophylactic drug for patients experiencing cluster headaches (CHs). Published papers usually state 240 to 480 mg taken in three divided doses give good results, ranging from 50% to 80%; others mention higher doses--720, even 1200 mg per day. In clinical practice we found we needed to adapt dosage to individual's time of attacks, in particular giving higher doses before going to bed to suppress severe nocturnal episodes. A few only required 120 mg daily. We therefore evolved a scheme for steady and progressive drug increase until satisfactory control had been achieved. To find the minimum dose of verapamil required to prevent episodic and chronic cluster headaches by supervising each individual and adjusting the dosage accordingly. Consecutive patients with episodic or chronic CH (satisfying International Headache Society (IHS) criteria) were started on verapamil 40 mg in the morning, 80 mg early afternoon, and 80 mg before going to bed. Patients kept a diary of all attacks, recording times of onset, duration, and severity. They were advised, verbally and in writing, to add 40 mg verapamil on alternate days, depending on their attack timing: with nocturnal episodes the first increase was the evening dose and next the afternoon one; when attacks occurred on or soon after waking, we advised setting an alarm clock 2 hours before the usual waking time and then taking the medication. Patients were followed-up at weekly intervals until attacks were controlled. They were also reviewed when a cluster period had ended, and advised to continue on the same dose for a further 2 weeks before starting systematic reduction. Chronic cluster patients were reviewed as often as necessary. Seventy consecutive patients, 52 with episodic CH during cluster periods and 18 with chronic CH, were all treated with verapamil as above. Complete relief from headaches was obtained in 49 (94%) of 52 with episodic, and 10 (55%) of 18 with chronic CH; the

  1. Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

    National Research Council Canada - National Science Library

    Gonçalves-Araújo, Tamara; Rajabi-Siahboomi, Ali R; Caraballo, Isidoro

    2010-01-01

    ...) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice...

  2. 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.

  3. Experimentally induced secondary cryptorchidism: Effects on growth ...

    African Journals Online (AJOL)

    Cryptorchidism may interfere with spermatogenesis but not the functions of the Leydig cells. This study investigated the effects of induced Secondary cryptorchidism growth performance of Djallonké lambs. A total of eighteen Djallonké lambs were assigned randomly to one of six treatments in a 2 × 3 factorial arrangement of ...

  4. Comparison of verapamil versus propranolol therapy in syndrome X.

    Science.gov (United States)

    Bugiardini, R; Borghi, A; Biagetti, L; Puddu, P

    1989-02-01

    The effects of oral verapamil, 320 mg daily, propranolol, 120 to 160 mg daily, and placebo were compared in 16 patients presenting with transient myocardial ischemia without evidence of coronary atherosclerosis or vasospasm on angiography (syndrome X). Testing was done according to a randomized double-blind crossover placebo-controlled trial consisting of 3 consecutive 7-day treatment periods with verapamil or propranolol or placebo. Patients underwent continuous 48-hour electrocardiographic monitoring before therapy (run-in phase) and during the last 2 days of each treatment period. A total of 391 episodes of diagnostic (greater than or equal to 0.15 mV) ST depression was recorded during the trial. Of these, 23 were symptomatic. None of the episodes occurred while the patients were asleep, 25% during exercise, 35% during minimal physical activity and 40% at rest. Rest included activities demanding mental arousal (conversation, reading or watching television). Heart rate at the onset of ST depression was higher (greater than or equal to 10 beats/min) than that observed in the 5 minutes preceding ischemia in 95% of the episodes. In the group as a whole, the average number of ischemic episodes per 24 hours was significantly reduced during propranolol therapy compared with placebo (0.7 +/- 0.6 vs 3.9 +/- 1.8; p less than 0.0005). No significant differences were seen during verapamil treatment (3.4 +/- 1.7 vs 3.9 +/- 1.8). It is concluded that transient myocardial ischemia in syndrome X is mostly precipitated by an increase in oxygen consumption, presumably due to a heightened sympathetic activity. Accordingly, beta blockers may represent the first line of treatment.

  5. 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....

  6. 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

    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...

  7. In Vitro Chemosensitization of Plasmodium falciparum to Antimalarials by Verapamil and Probenecid▿

    OpenAIRE

    Masseno, Victor; Muriithi, Steven; Nzila, Alexis

    2009-01-01

    We tested the effect of probenecid and verapamil in chemosensitizing Plasmodium falciparum to 14 antimalarials using the multidrug-resistant strain V1S and the drug-sensitive 3D7. Verapamil chemosensitizes V1S to quinine and chloroquine. Interestingly, probenecid profoundly chemosensitizes V1S to piperaquine. Thus, probenecid could be used to increase piperaquine efficacy in vivo.

  8. In vitro chemosensitization of Plasmodium falciparum to antimalarials by verapamil and probenecid.

    Science.gov (United States)

    Masseno, Victor; Muriithi, Steven; Nzila, Alexis

    2009-07-01

    We tested the effect of probenecid and verapamil in chemosensitizing Plasmodium falciparum to 14 antimalarials using the multidrug-resistant strain V1S and the drug-sensitive 3D7. Verapamil chemosensitizes V1S to quinine and chloroquine. Interestingly, probenecid profoundly chemosensitizes V1S to piperaquine. Thus, probenecid could be used to increase piperaquine efficacy in vivo.

  9. 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,

  10. 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.

  11. 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....

  12. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil

    Energy Technology Data Exchange (ETDEWEB)

    Safa, A.R. (Univ. of Chicago Medical Centers, IL (USA))

    1988-10-01

    Verapamil, a phenylalkylamine calcium channel blocker, has been shown to reverse multidrug resistance in tumor cells, possibly by increasing drug retention through interaction with an outward drug transporter of the resistant cells. In this study two photoactive radioactive analogs of verapamil, N-(p-azido(3,5-{sup 3}H)benzoyl)aminomethyl verapamil and N-(p-azido(3-{sup 125}I)salicyl)aminomethyl verapamil, were synthesized and used to identify the possible biochemical target(s) for verapamil in multidrug-resistance DC-3F/VCRd-5L Chinese hamster lung cells selected for resistance to vincristine. The results show that a specifically labeled 150- to 180-kDa membrane protein in resistant cells was immunoprecipitated with a monoclonal antibody specific for P-glycoprotein. Phenylalkylamine binding specificity was established by competitive blocking of specific photolabeling with the nonradioactive photoactive analogs as well as with verapamil. Photoaffinity labeling was also inhibited by 50 {mu}M concentrations of the calcium channel blockers nimodipine, nifedipine, nicardipine, azidopine, bepridil, and diltiazem and partially by prenylamine. Moreover, P-glycoprotein labeling was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at 0.2 {mu}M compared to that by verapamil at 8 {mu}M. These data provide direct evidence that P-glycoprotein has broad drug recognition capacity and that it serves as a molecular target for calcium channel blocker action in reversing multidrug resistance.

  13. Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids

    Directory of Open Access Journals (Sweden)

    Margaret Shanthi F

    2008-01-01

    Full Text Available Background : The calcium channel blocker, verapamil stimulates procollagenase synthesis in keloids and hypertrophic scars. Aim : To study the effect of verapamil in the treatment of hypertrophic scars and keloids and to evaluate the effect of verapamil on the rate of reduction of hypertrophic scars and keloids in comparison with triamcinolone. Methods : The study was a randomized, single blind, parallel group study in which 54 patients were allocated to to receive either verapamil or triamcinolone. Drugs were administered intralesionally in both groups. Improvement of the scar was measured using modified Vancouver scale and by using a centimeter scale serially till the scar flattened. Results : There was a reduction in vascularity, pliability, height and width of the scar with both the drugs after 3 weeks of treatment. These changes were present at one year of follow-up after stopping treatment. Scar pigmentation was not changed desirably by either drug. Length of the scars was also not altered significantly by either drug. The rate of reduction in vascularity, pliability, height and width of the scar with triamcinolone was faster than with verapamil. Adverse drug reactions were more with triamcinolone than with verapamil. Conclusion : Intralesional verapamil may be a suitable alternative to triamcinolone in the treatment of hypertrophic scars and keloids.

  14. Experimental synchronization of circuit oscillations induced by common telegraph noise.

    Science.gov (United States)

    Nagai, Ken; Nakao, Hiroya

    2009-03-01

    Experimental realization and quantitative investigation of common-noise-induced synchronization of limit-cycle oscillations subject to random telegraph signals are performed using an electronic oscillator circuit. Based on our previous formulation [K. Nagai, Phys. Rev. E 71, 036217 (2005)], dynamics of the circuit is described as random-phase mappings between two limit cycles. Lyapunov exponents characterizing the degree of synchronization are estimated from experimentally determined phase maps and compared with linear damping rates of phase differences measured directly. Noisy on-off intermittency of the phase difference as predicted by the theory is also confirmed experimentally.

  15. 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

  16. Ultrasound v. sham ultrasound for experimentally induced delayed ...

    African Journals Online (AJOL)

    In a double-blind controlled trial, delayed-onset muscle soreness (DOMS) was experimentally induced in both bicep muscles of 15 females. Sham US was applied to one bicep (n=15 biceps) and pulsed active US to the other bicep (n=15 biceps) of each participant, 48 and 72 h after induction of DOMS. Primary and ...

  17. Experimental observation of direct current voltage-induced phase ...

    Indian Academy of Sciences (India)

    September 2006 physics pp. 441–447. Experimental observation of direct current voltage-induced phase synchronization. HAIHONG LI1, WEIQING LIU1,2, QIONGLING DAI1 and JINGHUA XIAO1. 1School of Science, Beijing University of Posts and Telecommunications, Beijing 100876,. China. 2School of Science, Jiangxi ...

  18. 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)

  19. The effects of antivenom and verapamil on the haemodynamic actions of Chironex fleckeri (box jellyfish) venom.

    Science.gov (United States)

    Tibballs, J; Williams, D; Sutherland, S K

    1998-02-01

    The efficacy of antivenom and verapamil against Chironex fleckeri (box jellyfish) venom was investigated in monitored mechanically ventilated piglets. Chironex fleckeri tentacle extract alone, a mixture of tentacle extract with antivenom, and verapamil before tentacle extract were administered intravenously to groups of animals. Tentacle extract caused severe systemic hypotension, cardiac dysrrhythmias, pulmonary hypertension, haemolysis and hyperkalaemia. These effects were prevented by pre-incubation of tentacle extract with antivenom. Verapamil did not prevent any effect of venom, exacerbated cardiovascular collapse and increased mortality. We conclude that antivenom neutralizes the cardiovascular, haemolytic and hyperkalaemic effects of box jellyfish venom. Verapamil does not prevent any of these effects and is contra-indicated for treatment of envenomation.

  20. Managing hypertension in diabetic patients – focus on trandolapril/verapamil combination

    Directory of Open Access Journals (Sweden)

    Sanjib Kumar Sharma

    2007-09-01

    Full Text Available Sanjib Kumar Sharma1,3, Piero Ruggenenti1,2, Giuseppe Remuzzi1,2, 1Clinical Research Centre for Rare Diseases “Aldo e Cele Daccò”, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Italy; 2Unit of Nephrology, Azienda Ospedaliera, Ospedali Riuniti, Bergamo, Italy; 3Department of Medicine, BP Koirala Institute of Health Sciences, Dharan, NepalAbstract: Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressurereducing effect. Thus

  1. PAINLESS RADIAL ACCESS PROCEDURES WITH NICORANDIL: A COMPARATIVE ASSESSMENT WITH CONVENTIONAL VERAPAMIL - NITROGLYCERINE COCKTAIL

    OpenAIRE

    Jain T Kallarakkal; Rajesh T

    2012-01-01

    Background: Radial artery spasm is a major limitation of the transradial approach. This study was designed to compare the spasmolytic effect between nicorandil and the conventional cocktail of nitroglycerine and verapamil during transradial coronary procedures. Materials and methods: 200 patients were randomized into two groups to compare 8 mg of nicorandil and cocktail (mixture of normal saline, 5 mg of verapamil and 200 μg of nitroglycerin). Radial artery spasm and patient comfort in both t...

  2. 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.

  3. Gastritis induced by Helicobacter pylori infection in experimental rats.

    Science.gov (United States)

    Elseweidy, Mohamed M; Taha, Mona M; Younis, Nahla N; Ibrahim, Khadiga S; Hamouda, Hamdi A; Eldosouky, Mohamed A; Soliman, Hala

    2010-10-01

    Gastritis, an inflammation of gastric mucosa, may be due to many pathological factors and infection, such as with Helicobacter pylori. The use of experimental models of gastritis is important to evaluate the biochemical changes and study chemotherapeutic intervention. In a previous study we demonstrated an acute gastritis model induced by iodoacetamide. Our objective in this study was to evaluate a new gastritis model induced by H. pylori infection in experimental rats in terms of certain biomarkers in serum and mucosal tissues in addition to histopathological examination. Gastritis was induced in 20 albino Wistar rats by H. pylori isolated from antral biopsy taken from a 49-year-old male patient endoscopically diagnosed as having H. pylori infection. Another ten rats were used as controls. Serum gastrin, pepsinogen I activity, interleukin-6 (IL-6) and gastric mucosal myeloperoxidase (MPO) activity and prostaglandin E(2) (PGE(2)) were measured. Immunostaining for inducible nitric oxide synthase (iNOS), nitrotyrosine and DNA fragmentation were used to further evaluate H. pylori-induced gastritis. Serum gastrin, IL-6, mucosal MPO activity, and PGE(2) demonstrated significant increases joined with a decreased serum pepsinogen I activity (P gastritis models demonstrated massive oxidative stress and pronounced injury in mucosal tissue. Since our model in rats reflected the clinical picture of H. pylori infection, it can be considered as a consistent model to study chemotherapeutic intervention for this type of gastritis.

  4. 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...... allergic encephalitis. Furthermore, aAb-IL-6 carrying mice displayed increased plasma TNFalpha concentrations upon challenge with LPS. Taken together, induction of IL-6 autoantibodies was possible in different mouse strains. The autoantibodies influenced experimental inflammation. This immunotherapeutic...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  6. COMPARATIVE STUDY OF ORAL AND INTRALESIONAL VERAPAMIL IN PEYRONIE’S DISEASE

    Directory of Open Access Journals (Sweden)

    Saju P. R

    2017-05-01

    Full Text Available BACKGROUND Treatment of Peyronie's disease is a dilemma for the treating urologist. Part of this problem is due to an incomplete understanding of the aetiopathophysiology of the disease. Multiple nonsurgical treatment are available for Peyronie’s Disease (PD including calcium channel blocker verapamil, both oral and intraplaque injectable. The use of verapamil is based on its capacity to alter fibroblast function and promote collagen degradation. As a result, calcium channel antagonists may have the capacity to slow, prevent or even reverse plaque formation. There are many studies suggesting benefits of intraplaque verapamil injection. In our study, we aim to compare the outcomes of oral versus intraplaque verapamil injection in terms of pain reduction, decrease in curvature and improved sexual function. MATERIALS AND METHODS In this randomised study, 20 patients were randomly divided into 2 groups of 10 patients each (Group I patients were treated with oral verapamil and group II patients were treated with intraplaque verapamil injection. Results from both the groups were compared and interpreted in terms of change in plaque size, curvature, erectile function and pain. Size of plaque was assessed with the help of color Doppler in pre and post-treatment period. All the 20 patients were followed for 3 years after completion of treatment. None of the 20 patients lost to follow up. RESULTS 30% of group I patients (oral verapamil showed decreased plaque volume. Softening of plaque was noted in only 60% of the patients. Subjective erectile dysfunction improved in only 40% of the patients. In group, II patients who received intraplaque verapamil injection, 70% showed decreased plaque volume with improvement in penile curvature. There was softening of the plaque in all the patients in group II. Subjective erectile dysfunction improved in 60% of the patients. No local or systemic toxicity was noted except mild ecchymosis in 2 patients of group II

  7. Bioavailability enhancement of verapamil HCl via intranasal chitosan microspheres.

    Science.gov (United States)

    Abdel Mouez, Mamdouh; Zaki, Noha M; Mansour, Samar; Geneidi, Ahmed S

    2014-01-23

    Chitosan microspheres are potential drug carriers for maximizing nasal residence time, circumventing rapid mucociliary clearance and enhancing nasal absorption. The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres of verapamil hydrochloride (VRP) for intranasal delivery as an alternative to oral VRP which suffers low bioavailability (20%) due to extensive first pass effect. The microspheres were produced using a spray-drying and precipitation techniques and characterized for morphology (scanning electron microscopy), particle size (laser diffraction method), drug entrapment efficiency, thermal behavior (differential scanning calorimetry) and crystallinity (X-ray diffractometric studies) as well as in vitro drug release. Bioavailability of nasal VRP microspheres was studied in rabbits and the results were compared to those obtained after nasal, oral and intravenous administration of VRP solution. Results demonstrated that the microspheres were spherical with size 21-53 μm suitable for nasal deposition. The spray-drying technique was superior over precipitation technique in providing higher VRP entrapment efficiency and smaller burst release followed by a more sustained one over 6h. The bioavailability study demonstrated that the nasal microspheres exhibited a significantly higher bioavailability (58.6%) than nasal solution of VRP (47.8%) and oral VRP solution (13%). In conclusion, the chitosan-based nasal VRP microspheres are promising for enhancing VRP bioavailability by increasing the nasal residence time and avoiding the first-pass metabolism of the drug substance. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Verapamil toxicity dysregulates the phosphatidylinositol 3-kinase pathway.

    Science.gov (United States)

    Bechtel, Laura K; Haverstick, Doris M; Holstege, Christopher P

    2008-04-01

    Recent animal research and clinical case reports suggest benefit from high-dose insulin therapy (HDIT) for the treatment of calcium channel blocker (CCB) toxicity. One molecular signaling pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, that contributes to CCB toxicity and the efficacy of HDIT, was examined for a role in this phenomenon. A differentiated 3T3-L1 adipocyte model system was utilized to characterize metabolic and molecular signaling events dysregulated in response to acute CCB toxicity. Glucose uptake assays were performed in the presence of representatives of three classes of CCB drugs, and the ability of HDIT to reverse observed inhibition was assessed. Western blot analyses were utilized to probe which insulin-dependent signaling pathway was inhibited by CCB toxicity. Representative compounds from the dihydropyridine and phenylalkylamine classes of CCBs were more effective at inhibiting glucose uptake in differentiated 3T3-L1 adipocytes than a representative from the benzothiazepine class. Phosphorylation at serine 473 of the Akt protein (P-Akt), a protein representing a common pathway for insulin receptors (IR), insulinlike growth factor receptors (IGFR), and hybrid receptors formed by IR and IGFR subunits, was abolished in the presence of toxic doses of the phenylalkylamine CCB verapamil. Phosphorylation at serine 473 of Akt was rescued in the presence high concentrations of insulin. These data suggest that dysregulation of the insulin-dependent PI3K pathway is partially responsible for insulin resistance and the hyperglycemic state observed in response to acute CCB toxicity.

  9. Effects of Caffeine and Lycopene in Experimentally Induced Diabetes Mellitus.

    Science.gov (United States)

    Ozmen, Ozlem; Topsakal, Senay; Haligur, Mehmet; Aydogan, Ahmet; Dincoglu, Dilnur

    2016-04-01

    Diabetes mellitus (DM) is a global epidemic with increasing prevalence. The disease is chronic in nature, and patients must use antidiabetic drugs or insulin during their lifespan. Because of the difficulty of using injectable insulin preparations, patients and practitioners prefer to use oral antidiabetic drugs for prophylaxis and treatment. There are, however, numerous adverse effects of antidiabetic drugs and rapidly increasing attention is being paid to new nutraceutical drugs with fewer adverse effects. The purpose of this study was to evaluate the effects of caffeine and lycopene on streptozotocin (STZ)-induced DM in rats. Caffeine and lycopene were administered to the study groups by oral gavages for 1 month whereafter experimental diabetes was induced in 90 rats in 6 groups. There were no pathological effects of lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were observed in STZ-treated groups. Caffeine and lycopene decreased the pathological findings and lowered the blood and urine glucose levels in the rats with STZ-induced DM, whereas these compounds increased serum insulin levels. This study showed that caffeine and lycopene provided protective effects against experimentally induced DM. The protective effects of lycopene were observed to be much greater than those of caffeine.

  10. Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II)

    DEFF Research Database (Denmark)

    1990-01-01

    The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled multicenter trial. Eight hundred seventy-eight patients started treatment with verapamil, 360 mg/day, and 897 patients.......79, hazard ratio, 1.05; 95% confidence limits, 0.72 to 1.54), and major event rates 24.9 and 24.9% (p = 1.0, hazard ratio 0.98; 95% confidence limits 0.72 to 1.39). Long-term treatment with verapamil after an acute myocardial infarction caused a significant reduction in major events, and the positive effect...... with placebo. Treatment started in the second week after admission and continued for up to 18 months (mean 16 months). Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group. The 18-month mortality rates were 11.1 and 13.8% (p = 0...

  11. 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

  12. 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

    Background Keloids and hypertrophic scar/span>s 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 scar/span>s. 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 scar/span>s 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 hypertrophic scar/span>s treatment. Verapamil could act as an effective alternative modality in the prevention and treatment of keloid and

  13. 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.

  14. 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.

  15. The effect of experimentally-induced subacromial pain on proprioception.

    Science.gov (United States)

    Sole, Gisela; Osborne, Hamish; Wassinger, Craig

    2015-02-01

    Shoulder injuries may be associated with proprioceptive deficits, however, it is unknown whether these changes are due to the experience of pain, tissue damage, or a combination of these. The aim of this study was to investigate the effect of experimentally-induced sub-acromial pain on proprioceptive variables. Sub-acromial pain was induced via hypertonic saline injection in 20 healthy participants. Passive joint replication (PJR) and threshold to detection of movement direction (TTDMD) were assessed with a Biodex System 3 Pro isokinetic dynamometer for baseline control, experimental pain and recovery control conditions with a starting position of 60° shoulder abduction. The target angle for PJR was 60° external rotation, starting from 40°. TTDMD was tested from a position of 20° external rotation. Repeated measures ANOVAs were used to determine differences between PJR absolute and variable errors and TTDMD for the control and experimental conditions. Pain was elicited with a median 7 on the Numeric Pain Rating Scale. TTDMD was significantly decreased for the experimental pain condition compared to baseline and recovery conditions (≈30%, P = 0.003). No significant differences were found for absolute (P = 0.152) and variable (P = 0.514) error for PJR. Movement sense was enhanced for the experimental sub-acromial pain condition, which may reflect protective effects of the central nervous system in response to the pain. Where decreased passive proprioception is observed in shoulders with injuries, these may be due to a combination of peripheral tissue injury and neural adaptations that differ from those due to acute pain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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...

  17. Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses

    Science.gov (United States)

    Matre, Dagfinn; Hu, Li; Viken, Leif A.; Hjelle, Ingri B.; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

    2015-01-01

    Study Objectives: Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. Design: A paired crossover study. Intervention: Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Setting: Laboratory experiment at research center. Participants: Self-reported healthy volunteers (n = 21, age range: 18–31 y). Measurements and Results: Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Conclusion: Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. Citation: Matre D, Hu L, Viken LA, Hjelle IB, Wigemyr M, Knardahl S, Sand T, Nilsen KB. Experimental sleep restriction facilitates pain and electrically induced cortical responses. SLEEP 2015;38(10):1607–1617. PMID:26194577

  18. 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

  19. The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate.

    Science.gov (United States)

    Ramasamy, Sharmaine; Isbister, Geoffrey K; Seymour, Jamie E; Hodgson, Wayne C

    2004-05-01

    Using a new technique to extract venom from the nematocysts, the efficacy of CSL box jellyfish antivenom (AV) and adjunct therapies, verapamil and magnesium sulfate (MgSO(4)), were investigated against the in vivo cardiovascular effects of Chironex fleckeri venom in anaesthetised rats. C. fleckeri venom (30 microg/kg; i.v.) produced a transient hypertensive response followed by hypotension and cardiovascular collapse within 4 min of administration. Prophylactic treatment of anaesthetised rats with CSL box jellyfish AV (3000 U/kg; i.v.) did not have any effect on the venom-induced pressor response, but prevented cardiovascular collapse in four out of 10 animals. Administration of verapamil (20mM@0.25 ml/min; i.v.) either alone or in combination with AV, did not have any effect on the C. fleckeri venom-induced pressor response nor the consequent hypotension or cardiovascular collapse of animals. However, the administration of verapamil negated the partially protective effects of AV. Concurrent artificial respiration of animals with the above treatments did not attenuate the C. fleckeri venom-induced cardiovascular effects. MgSO(4) (0.05-0.07M@0.25 ml/min; i.v.) alone did not have any effect on the venom-induced pressor response nor the consequent cardiovascular collapse of animals. However, although combined AV and MgSO(4) administration could not inhibit the transient pressor effect following the administration of C. fleckeri venom, it prevented cardiovascular collapse in all animals. We show for the first time, the cardiovascular effects of a C. fleckeri venom sample free of tentacular contamination and the potential of MgSO(4) as an adjunct therapy for the treatment of potentially fatal C. fleckeri envenomings.

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

    DEFF Research Database (Denmark)

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul

    2009-01-01

    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...... 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 (0 degrees...... -105 degrees) at a speed of approximately 120 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 muscles...

  1. 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

    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...... 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......-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...

  2. 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.

  3. 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...... with the acceleration of the treadmill depends on the frequency of the movement, such that pedestrians (on average) add to the overall modal mass for low frequency motion and subtract from the overall modal mass at higher frequencies....

  4. 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

    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 (PVRP at each of the concentrations tested, but MM 36, CTS 27 and CTS 41 demonstrated...... 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...

  5. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia.

    Science.gov (United States)

    Terkelsen, Astrid J; Bach, Flemming W; Jensen, Troels S

    2008-08-01

    Complex regional pain syndrome is a painful condition of unknown etiology. Clinical and experimental observations suggest that limb immobilization may induce symptoms and signs characteristic of complex regional pain syndrome. This study examined the effect of forearm immobilization on regional sensory and autonomic functions in healthy subjects. Thermal and mechanical sensitivity, skin temperature, and vasoconstrictor responses were measured in 30 healthy subjects before and 0, 3, and 28 days after scaphoid cast immobilization. Fifteen subjects served as nonimmobilized controls. At cast removal, 27 subjects experienced pain at joint movement. Cast immobilization induced cold hyperalgesia in glabrous and hairy skin on the immobilized hand and induced significant skin temperature differences between the control and the immobilized hand at cast removal and after 3 days. Immobilization also reduced pain threshold at skin fold testing at all time points after cast removal. All measures except pain threshold at skin fold testing were normalized after 28 days. Immobilization did not affect thermal detection, heat pain, and pressure pain thresholds; resting skin perfusion; or vasoconstrictor responses induced by mental stress or deep inspirations. Four weeks of forearm immobilization caused transient changes in skin temperature, mechanosensitivity, and thermosensitivity, without alteration in the sympathetically mediated vascular tone.

  6. 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.

  7. Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

    Science.gov (United States)

    Rivera, Antonio; Yáñez, Antonio; León-Tello, Gloria; Gil, Constantino; Giono, Silvia; Barba, Eduardo; Cedillo, Lilia

    2002-01-01

    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. PMID:12057023

  8. 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.

  9. Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis

    Directory of Open Access Journals (Sweden)

    Hidelberto Matos Silva

    Full Text Available ABSTRACT Neurocysticercosis (NCC is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4 on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT and BALB/c (IL-4-KO mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

  10. Hypolipidemic effect of arborium plus in experimentally induced hypercholestermic rabbits.

    Science.gov (United States)

    Murty, Devarakonda; Rajesh, Enjamoori; Raghava, Doonaboina; Raghavan, Tangaraj Vijaya; Surulivel, Mukanthan Karupiah Munirajan

    2010-06-01

    Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of the ayurvedic herbal formulation Arborium Plus [Hyppophae ramnoides L. fruit juice (S) and Rhododendron arboreum Sm. Linn flower juice (R) in a 1:4 ratio] on triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), atherogenic index (AI), high-density lipoprotein (HDL), and high-sensitivity c-reactive protein (hs CRP) in experimentally induced hypercholesterolemic rabbits. Four groups of rabbits were subjected to different treatments for 8 weeks: control group, CHOL group (1% w/w cholesterol for 8 weeks), S+R group (1% w/w cholesterol and Arborium Plus for 8 weeks), and A group (1% w/w cholesterol and atorvastatin for 8 weeks). The results showed significant increases in TG, TC, LDL, AI, and hs CRP in hypercholesterolemic rabbits which was significantly reduced in Arborium Plus-treated hypercholesterolemic rabbits. The data demonstrated that the Arborium Plus formulation was associated with hypolipidemic effects in experimentally induced hypercholesterolemic rabbits.

  11. Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical Responses.

    Science.gov (United States)

    Matre, Dagfinn; Hu, Li; Viken, Leif A; Hjelle, Ingri B; Wigemyr, Monica; Knardahl, Stein; Sand, Trond; Nilsen, Kristian Bernhard

    2015-10-01

    Sleep restriction (SR) has been hypothesized to sensitize the pain system. The current study determined whether experimental sleep restriction had an effect on experimentally induced pain and pain-elicited electroencephalographic (EEG) responses. A paired crossover study. Pain testing was performed after 2 nights of 50% SR and after 2 nights with habitual sleep (HS). Laboratory experiment at research center. Self-reported healthy volunteers (n = 21, age range: 18-31 y). Brief high-density electrical stimuli to the forearm skin produced pinprick-like pain. Subjective pain ratings increased after SR, but only in response to the highest stimulus intensity (P = 0.018). SR increased the magnitude of the pain-elicited EEG response analyzed in the time-frequency domain (P = 0.021). Habituation across blocks did not differ between HS and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039). Pressure pain threshold of the trapezius muscle region also decreased after SR (P = 0.017). Sleep restriction (SR) increased the sensitivity to pressure pain and to electrically induced pain of moderate, but not low, intensity. The increased electrical pain could not be explained by a difference in habituation. Increased response magnitude is possibly related to reduced processing within the somatosensory cortex after partial SR. © 2015 Associated Professional Sleep Societies, LLC.

  12. Experimental and analytical studies on pedestrian induced footbridge vibrations

    DEFF Research Database (Denmark)

    Gudmundsson, Gudmundur Valur; Ingólfsson, Einar Thór; Einarsson, Baldvin

    2007-01-01

    This paper presents results from experimental study on human-induced vibrations of three lively footbridges in Reykjavik. The project was funded by the Icelandic Public Roads Administration with two main focus areas; validating the FE-models used at the design stage in terms of dynamic characteri......This paper presents results from experimental study on human-induced vibrations of three lively footbridges in Reykjavik. The project was funded by the Icelandic Public Roads Administration with two main focus areas; validating the FE-models used at the design stage in terms of dynamic...... with two equal spans crossing the same highway and was built in 2000. A commercially available finite element program (SAP2000) was used in the design phase to model the bridges. The FE-models were updated after the initial tests in order to have the frequencies and damping of the fundamental vibration...... 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...

  13. Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by PAMPA.

    Science.gov (United States)

    Alvarez-Figueroa, M J; Contreras-Garrido, B C; Soto-Arriaza, M A

    2015-04-01

    Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA) permeability was studied using lipids not yet reported for this model in order to facilitate the quantification of drug permeability. These lipids are 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using the lipids mentioned above was compared with lecithin-PC. The results show that verapamil permeability depends on the kind of lipid used, in the order DMPC > DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times larger than those obtained in lecithin-PC for all the concentrations of the drug used. Naproxen shows similar permeability than verapamil; however, the permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC were used. This behavior could be explained by a difference between the drug net charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil permeability increases in all lipid systems; however, the relative verapamil permeability respect to lecithin-PC did not show any significant increase. This result is likely due to the promoting effect of cholesterol, which is not able to compensate for the large increase in verapamil permeability observed in lecithin-PC. With respect to naproxen, its permeability value and relative permeability respect lecithin-PC not always increased in the presence of cholesterol. This result is probably attributed to the negative charge of naproxen rather than its molecular weight. The lipid systems studied have an advantage in drug permeability quantification, which is mainly related to the charge of the molecule and not to its molecular weight or to cholesterol used as an absorption promoter.

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

    Science.gov (United States)

    Diederichsen, Louise Pyndt; Winther, Annika; Dyhre-Poulsen, Poul; Krogsgaard, Michael R; Nørregaard, Jesper

    2009-04-01

    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 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 (0 degrees -105 degrees) at a speed of approximately 120 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 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 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 that acute pain both subacromially and in the supraspinatus muscle modulates coordination of the shoulder muscles during voluntary movements. During painful conditions, an increased activity was detected in the antagonist (latissimus), which support the idea that localized pain affects muscle activation in a way that protects the painful structure. Further, the changes in muscle activity following subacromial pain induction tend to expand the subacromial space and thereby decrease the load

  15. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    Science.gov (United States)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  16. Method for inducing experimental pneumococcal meningitis in outbred mice

    Directory of Open Access Journals (Sweden)

    Cintorino Marcella

    2004-09-01

    Full Text Available Abstract Background Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines. Results In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4, and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 102 colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans. Conclusions The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.

  17. 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.

  18. Mechanisms of blast induced brain injuries, experimental studies in rats.

    Science.gov (United States)

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. The protective effect of bee venom against verapamil embryotoxicity during prenatal liver and kidney development of mice Mus musculus

    Directory of Open Access Journals (Sweden)

    Amin A. Seleem

    2016-05-01

    Full Text Available Verapamil is a calcium channel blocker that has been widely used in the treatment of cardiovascular abnormalities, hypertension and angina pectoris. The present study investigates the effect of bee venom against verapamil embryotoxicity, bee venom (BV is characterized with anticancer, anti-inflammatory, anti-rheumatoid, pain-relieving and neuroprotective agents. The current study was carried out on 70 pregnant female mice which were divided into two main groups, the first main group divided into three subgroups, control, treated with single and twice dose daily of verapamil (40 mg/kg that was treated from zero day of gestation to scarification of females at E10. The second main group that was treated from the seventh day of gestation was divided into four subgroups, control, treated with single dose daily of verapamil (40 mg/kg, injected with bee venom (150 μg/kg/BW and treated with verapamil combined with bee venom, the females were sacrificed at E14 and E17. The results of this study showed that verapamil treated groups once or twice daily in the first main experiment showed abortion and resorption of uteri embryos. In the second main experiment, developing liver and kidney at E14 and E17 in verapamil treated group showed abnormal architecture of histological picture and alterations of immunohistochemical expression of heat shock protein and BAK that were associated with ultrastructure abnormalities at E17. Bee venom treated group showed the similar structure as control, verapamil combined with bee venom treated group exhibited amelioration against verapamil embryotoxicity. In conclusion, bee venom could be considered as a therapeutic agent and it has a curative effect against the toxicity of verapamil during development of liver and kidney.

  20. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    Science.gov (United States)

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy. © The Author(s) 2014.

  1. 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.

  2. Acute pulmonary injury induced by experimental muscle trauma.

    Science.gov (United States)

    Sombra, Márcia Andréa da Silva Carvalho; Vasconcelos, Marcelo Pinho Pessoa de; Guimarães, Sergio Botelho; Escalante, Rodrigo Dornfeld; Garcia, José Huygens Parente; Vasconcelos, Paulo Roberto Leitão de

    2011-01-01

    To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. 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 2,0 ml 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. 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. Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.

  3. Antioxidant Effects of Probiotics in Experimentally Induced Peritonitis.

    Science.gov (United States)

    Erginel, Basak; Aydin, Fatih A; Erginel, Turgay; Tanik, Canan; Abbasoglu, Semra D; Soysal, Feryal G; Keskin, Erbug; Celik, Alaaddin; Salman, Tansu

    2016-02-01

    An experimental study was performed to evaluate the protective effects of probiotics on gut mucosa in peritonitis through antioxidant mechanisms. Thirty-two male Wistar albino rats were divided equally into four groups. The rats in Group 1 (control group) underwent laparotomy only. In group 2 (peritonitis group), peritonitis was induced in the rats by the cecal ligation and puncture (CLP) model. In group 3, the rats were treated with probiotics for five days after CLP-induced peritonitis. The last group of rats (group 4) were fed probiotics for five days before the CLP procedure and five days after the surgery. On the fifth day after surgery, all rats were killed, and tissue samples from the terminal ileum were obtained to evaluate the activities of myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH). Histopathologic examinations were also performed to evaluate the grade of intestinal injury. Myeloperoxidase and MDA activities were increased, GSH concentrations were decreased in group 2, compared with group 1. Intestinal MPO activities in group 4 were decreased compared with group 1 and group 2, indicating a reduction in oxidant activity. Malondialdehyde decreased in group 3 and decreased even more in group 4, compared with the peritonitis group (group 2). Glutathione concentrations were increased in group 4 compared with group 2 and group 3 (p peritonitis, which may be related to antioxidant mechanisms. This antioxidant effect of probiotics might occur when pre-conditioning with probiotics before peritonitis because there is sufficient time to prepare the tissues for oxidative damage.

  4. [Verapamil in conjunction with pressure therapy in the treatment of pathologic scar due burn injury].

    Science.gov (United States)

    Ramos-Gallardo, Guillermo; Miranda-Altamirano, Ariel; Valdes-López, Rebeca; Figueroa-Jiménez, Sandra; García-Benavides, Leonel

    2016-01-01

    Keloids and hypertrophic scars are dermal fibro-proliferative disorders unique to humans. Their treatment is a true challenge with multiple options, but not all the time with good results. Unfortunately this problem is not uncommon in patients with history of burn injury. The aim of this article is to evaluate the use of verapamil and pressure garments in patients with hypertrophic or keloid scar caused by burn injury. We included patients with a hypertrophic or keloid scar caused by burn injury candidate to treatment with pressure garment. The pathologic scars were evaluated by serial photographic records, Vancouver and Posas scales. The scales of Vancouver and Posas were compared with t Student. We included 13 scars in 11 patients. Four scars were located in the legs, 4 in the arms, 4 in the face-neck and 1 in the abdomen. The dose of verapamil was calculated .03mg per kg. Injections were scheduled every 7 to 10 days until complete 6 sessions. Taking in count Posas scale, patients referred improvement in pigmentation (.01), thickness (.005), pliability (.01) and surface area (.004). In the Vancouver scale the observers mentioned improvement in elevation (.008), pigmentation (.014), vascularity (.022), flexibility (.014) and pruritus (.003). No adverse effects were found in verapamil injection. Verapamil was useful in conjunction with pressure garment to improve the condition of the keloid and hypertrophic scar caused by burn.

  5. Regression of outflow tract obstruction subsequent to treatment with verapamil in hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Frandsen, F; Mickley, H

    1990-01-01

    A 29-year-old man suffering from hypertrophic obstructive cardiomyopathy was treated with verapamil 240 mg daily for 4.5 years. During this period the symptoms were reduced, and an intraventricular gradient diminished from 80 to 20 mm Hg, possibly due to a decrease in left ventricular ejection fr...

  6. Ivabradin and Verapamil Sr efficacy in treatment of coronary heart disease accompanied by bronchial obstructive diseases

    Directory of Open Access Journals (Sweden)

    Petrov V.I.

    2011-06-01

    Full Text Available The aim of the research is a comparative investigation of Ivabradin vs Verapamil SR of antianginal/antiischemic activity, physical exertion tolerance and life quality of patients with coronary heart disease (CHD accompanied by bronchial obstructive diseases. Parallel groups of patients have been examined for a 16-week period. Ivabradin (average dose — 14mg/day or Verapamil SR (average dose — 443mg/day were administered to ischemic patients (n=84 with postinfarction cardiosclerosis, stable angina (class l-ll and painless myocardial ischemia. Concomitant bronchial obstructive deseases included controlled/partly controlled bronchial asthma or chronic obstructive pulmonary disease (stage II-III. Both medications have demonstrated the same antianginal/antiischemic activity and have improved physical exertion tolerance. Ivabradin was more effective for heart rate (HR aim level and 24-hour HR control. Ivabradin advantages were more expressed by changing of NYHA class (from class II to class I and increase of 6MWD. In conclusion Ivabradin has demonstrated its effectiveness in life quality improvement. Ivabradin and Verapamil SR did not cause complications in concomitant asthma/COPD and were good tolerated. It was determined that Ivabradin is a good Verapamil SR alternative for CHD treatment in case of bronchial obstructive concomitant diseases

  7. 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

  8. An experimental model of vitreous motion induced by eye rotations.

    Science.gov (United States)

    Bonfiglio, Andrea; Lagazzo, Alberto; Repetto, Rodolfo; Stocchino, Alessandro

    2015-01-01

    During eye rotations the vitreous humour moves with respect to the eye globe. This relative motion has been suggested to possibly have an important role in inducing degradation of the gel structure, which might lead to vitreous liquefaction and/or posterior vitreous detachment. Aim of the present work is to study the characteristics of vitreous motion induced by eye rotations. We use an experimental setup, consisting of a Perspex model of the vitreous chamber that, for simplicity, is taken to have a spherical shape. The model is filled with an artificial vitreous humour, prepared as a solution of agar powder and hyaluronic acid sodium salt in deionised water, which has viscoelastic mechanical properties similar to those of the real vitreous. The model rotates about an axis passing through the centre of the sphere and velocity measurements are taken on the equatorial plane orthogonal to the axis of rotation, using an optical technique. The results show that fluid viscoelasticity has a strong influence on flow characteristics. In particular, at certain frequencies of oscillation of the eye model, fluid motion can be resonantly excited. This means that fluid velocity within the domain can be significantly larger than that of the wall. The frequencies for which resonant excitation occurs are within the range of possible eye rotations frequencies. Therefore, the present results suggest that resonant excitation of vitreous motion is likely to occur in practice. This, in turn, implies that eye rotations produce large stresses on the retina and within the vitreous that may contribute to the disruption of the vitreous gel structure. The present results also have implications for the choice of the ideal properties for vitreous substitute fluids.

  9. Pathogenesis of rhinitis in rats with experimentally induced hypothyroidism.

    Science.gov (United States)

    Eyigor, Hulya; Basak, Sema; Kozaci, Didem; Culhaci, Nil; Dost, Turhan; Ulutas, Pinar

    2012-01-01

    Hypothyroidism is accepted as one of the hormonal factors leading to non-allergic rhinitis. Nasal obstruction and runny nose due to an increase in submucosal connective tissue and mucous gland hypertrophy are the prominent symptoms in hypothyroidism-induced rhinitis at humans. The aim of this study was to analyze the biochemical and histopathological changes in the nasal mucosa of the rats with thyroidectomy-induced hypothyroidism and to compare them with those of a control group. A total of 60 adult male Wistar Albino rats were included in the study. The rats constituting the test and the control groups were randomly divided into 3 subgroups (T1-3 and C 1-3). While the rats in the test group underwent thyroidectomy, in the control group the incision was sutured without any interventions after exposure of thyroid tissues of the rats. The nasal and paranasal sinus regions of all the rats were carefully dissected and tissue samples were obtained for pathological examinations. In the rats in T1, T2, and T3, the decrease in serum glucuronic acid levels before and after thyroidectomy was statistically significant (p = 0.001, p = 0.003, and p = 0.002, respectively). The difference between the test and the control groups was statistically significant in terms of inflammation at the end of 12 weeks (p = 0.002). An increase in acid mucopolysaccharidase production due to TSH has been suggested to cause congestion in tissues. Although our study supports the data in the literature up to date, we consider that further clinical and experimental studies are necessary for this verification.

  10. 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

    A double-blind randomized controlled trial with a paired split-scar design compared verapamil, an L-type Ca2+ channel antagonist, and triamcinolone for prevention of keloid recurrence after excision. Ca2+ channel blocking activity of verapamil in keloid cells was explored. One keloid was excised...... 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...

  11. The Cell Nucleus in Physiological and Experimentally Induced Hypometabolism

    Science.gov (United States)

    Malatesta, M.

    The main problem for manned space mission is, at present, represented by the mass penalty associated to the human presence. An efficient approach could be the induction of a hypometabolic stasis in the astronauts, thus drastically reducing the physical and psychological requirements of the crew. On the other hand, in the wild, a reduction in resource consumptions physiologi- cally occurs in certain animals which periodically enter hibernation, a hypometabolic state in which both the energy need and energy offer are kept at a minimum. During the last twelve years, we have been studying different tissues of hibernating dormice, with the aim of analyzing their features during the euthermia -hibernation-arousal cycle as well as getting insight into the mechanisms allowing adaptation to hypometabolism. We paid particular attention to the cell nucleus, as it is the site of chief metabolic functions, such as DNA replication and RNA transcription. Our observations revealed no significant modification in the basic features of cell nuclei during hibernation; however, the cell nuclei of hibernating dormice showed unusual nuclear bodies containing molecules involved in RNA pathways. Therefore, we supposed that they could represent storage/assembly sites of several factors for processing some RNA which could be slowly synthesised during hibernation and rapidly and abundantly released in early arousal in order to meet the increased metabolic needs of the cell. The nucleolus also underwent structural and molecular modifications during hibernation, maybe to continue important nucleolar functions, or, alternatively, permit a most efficient reactivation upon arousal. On the basis of the observations made in vivo , we recently tried to experimentally induce a reversible hypometabolic state in in vitro models, using cell lines derived from hibernating and non-hibernating species. By administering the synthetic opioid DADLE, we could significantly reduce both RNA transcrip- tion and

  12. 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

  13. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats

    Directory of Open Access Journals (Sweden)

    Bernhard Kraemer

    2014-01-01

    Full Text Available Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1, brushing of parietal peritoneum only (group 2, sharp excision of parietal peritoneum closed with interrupted sutures (group 3, ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4, bipolar electrocoagulation of the peritoneum (group 5, and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6. Upon second look, there were significant differences in the adhesion incidence between the groups (P<0.01. Analysis of the fraction of adhesions showed that groups 2 (0% and 5 (4% were significantly less than the other groups (P<0.01. Furthermore, group 6 (69% was significantly higher than group 1 (48% (P<0.05 and group 4 (47% (P<0.05. There was no difference between group 3 (60% and group 6 (P=0.2. From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models.

  14. Chronic toxicity of verapamil on juvenile rainbow trout (Oncorhynchus mykiss): effects on morphological indices, hematological parameters and antioxidant responses.

    Science.gov (United States)

    Li, Zhi-Hua; Velisek, Josef; Zlabek, Vladimir; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2011-01-30

    In this study, the toxic effects of verapamil (VRP) were studied on juvenile rainbow trout, Oncorhynchus mykiss, by chronic semi-static bioassay. Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg/L) for 0, 21 and 42 d. Multiple biomarkers were measured, including morphological indices, hematological parameters and antioxidant responses of different tissues (brain, gill, liver, muscle and intestine). Based on the results, there was no significant change in all parameters measured in fish exposed to VRP at environmental related concentration, but VRP-induced stress in fish exposed to higher concentrations reflected the significant changes of physiological and biochemical responses. Through principal component analysis and integrated biomarker response assessment, effects induced by VRP-stress in each test group were distinguished. Additionally, all parameters measured in this study displayed various dependent patterns to VRP concentrations and exposure time using two-way ANOVA statistic analysis. In short, the multiple responses in fish indicated that VRP induced physiological stress and could be used as potential biomarkers for monitoring residual VRP in aquatic environment; but molecular and genetic mechanisms of these physiological responses in fish are not clear and need to be further studied. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. 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

  16. Experimental glomerulonephritis induced by hydrocarbon exposure: a systematic review.

    Science.gov (United States)

    Ravnskov, Uffe

    2005-12-14

    Much epidemiological evidence suggests that hydrocarbon exposure may induce glomerulonephritis and worsen its course in many patients. The mechanisms are unknown, however, no specific microscopic pattern has been identified, and it has also been argued that hydrocarbon exposure causes tubular damage mainly. Studying experimental animals may best answer these questions, and as no systematic review of glomerulonephritis produced experimentally by hydrocarbon exposure has been performed previously, I found it relevant to search for and analyse such studies. Animal experiments having mimicked human glomerulonephritis by hydrocarbon exposure were sought on Medline and Toxnet Twenty-six experiments using thirteen different hydrocarbons were identified. Several human subtypes were observed including IgA nephritis, mesangial, proliferative and extracapillary glomerulonephritis, focal and focal-segmental sclerosis, minimal change nephropathy, anti-GBM and anti-TBM nephritis, and glomerulonephritis associated with peiarteritis nodosa. Glomerular proteinuria was seen in 10/12 experiments that included urine analyses, and renal failure in 5/8 experiments that included measurements of glomerular function. All experiments resulted in various degrees of tubular damage as well. In most studies, where the animals were examined at different times during or after the exposure, the renal microscopic and functional changes were seen immediately, whereas deposits of complement and immunoglobulins appeared late in the course, if at all. These experiments are in accord with epidemiological evidence that hydrocarbon exposure may cause glomerulonephritis and worsen renal function. Probable mechanisms include an induction of autologous antibodies and a disturbance of normal immunological functions. Also, tubular damage may increase postglomerular resistance, resulting in a glomerular deposition of macromolecules. In most models a causal role of glomerular immune complex formation was

  17. Experimental glomerulonephritis induced by hydrocarbon exposure: A systematic review

    Directory of Open Access Journals (Sweden)

    Ravnskov Uffe

    2005-12-01

    Full Text Available Abstract Background Much epidemiological evidence suggests that hydrocarbon exposure may induce glomerulonephritis and worsen its course in many patients. The mechanisms are unknown, however, no specific microscopic pattern has been identified, and it has also been argued that hydrocarbon exposure causes tubular damage mainly. Studying experimental animals may best answer these questions, and as no systematic review of glomerulonephritis produced experimentally by hydrocarbon exposure has been performed previously, I found it relevant to search for and analyse such studies. Methods Animal experiments having mimicked human glomerulonephritis by hydrocarbon exposure were sought on Medline and Toxnet Results Twenty-six experiments using thirteen different hydrocarbons were identified. Several human subtypes were observed including IgA nephritis, mesangial, proliferative and extracapillary glomerulonephritis, focal and focal-segmental sclerosis, minimal change nephropathy, anti-GBM and anti-TBM nephritis, and glomerulonephritis associated with peiarteritis nodosa. Glomerular proteinuria was seen in 10/12 experiments that included urine analyses, and renal failure in 5/8 experiments that included measurements of glomerular function. All experiments resulted in various degrees of tubular damage as well. In most studies, where the animals were examined at different times during or after the exposure, the renal microscopic and functional changes were seen immediately, whereas deposits of complement and immunoglobulins appeared late in the course, if at all. Conclusion These experiments are in accord with epidemiological evidence that hydrocarbon exposure may cause glomerulonephritis and worsen renal function. Probable mechanisms include an induction of autologous antibodies and a disturbance of normal immunological functions. Also, tubular damage may increase postglomerular resistance, resulting in a glomerular deposition of macromolecules. In most

  18. Verapamil versus digoxin and acute versus routine serial cardioversion for the improvement of rhythm control for persistent atrial fibrillation

    NARCIS (Netherlands)

    Hemels, Martin E. W.; Van Noord, Trudeke; Crijns, Harry J. G. M.; Van Veldhuisen, Dirk J.; Veeger, Nic J. G. M.; Bosker, Hans A.; Wiesfeld, Ans C. P.; Van den Berg, Maarten P.; Ranchor, Adelita V.; Van Gelder, Isabelle C.

    2006-01-01

    OBJECTIVES The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular

  19. Effects of training and of verapamil on exercise capacity in patients recovering from myocardial infarction. A double-blind study.

    Science.gov (United States)

    Rossi, P; Giordano, A; Tamiz, A; Schiavo, B; Minuco, G

    1979-01-01

    Physical training causes an increase of aerobic capacity in normal and cardiac patients. The influences of training plus placebo and training plus verapamil have been studied in a double-blind randomized trial on 40 patients recovering from actue myocardial infarction. The two groups were comparable as to clinical characteristics, initial work capacity, and amount of stress tolerated during the training sessions. The training produced a significant increase of total work capacity and maximum VO2, in both groups; the difference between the means of the two groups was not significant. The variation of heart rate, rate pressure product at different work loads and cardiac volume after training were significantly lower in the verapamil group. The anginal threshold did not change in the placebo group and showed a trend to increase in patients treated with verapamil. These results suggest that carefully observed rehabilitation markedly improves the physical capacity of the patients after acute myocardial infarction. Such improvement is enhanced by treatment with verapamil.

  20. Anticoccidial effect of mananoligosacharide against experimentally induced coccidiosis in broiler.

    Science.gov (United States)

    Chand, Naila; Faheem, Hassan; Khan, Rifat Ullah; Qureshi, Muhammad Subhan; Alhidary, Ibrahim A; Abudabos, Alaeldein M

    2016-07-01

    The aim of this study was to find the effect of mananoligosacharide (MOS) in comparison with amprolium hydrochloride on performance and integrity of gut in experimentally induced coccidiosis in broiler. A total of 300, day-old male broiler chickens (Ross 308) was randomly allocated to four treatments. Each group was further divided into five replicates of 15 birds each. Group A was kept as control; group B was contaminated with Eimeria tenella, while groups C and D were infected with E. tenella and treated with MOS (0.8 g/kg feed) and anticoccidial drug, amprolium hydrochloride (12 g/100 l water), respectively. The results showed that weight gain, feed intake, and feed conversion ratio (FCR) were significantly higher (P coccidiosis during 5th, 7th, 10th, and 12th day post infection (dpi). Furthermore, the OPG was significantly lower (P < 0.05) in infected groups treated with MOS and amprolium at the studied periods (5, 7, and 10 dpi). At 12 dpi, the infected group treated with MOS showed significantly lower OPG compared to the other groups suggesting the effectiveness of MOS in comparison to amprolium. The result of pinpoint hemorrhages, thickness of cecal wall, bloody fecal contents, and mucoid contents in the cecum were significant highly (P < 0.05) in birds fed with infected oocytes. It was also noted that the differences were not significant in these parameters between amprolium and MOS-treated birds showing the effectiveness of the prebiotic agent. It was concluded from the results of the present study that MOS improved growth performance and reversed the lesions of E. tenella.

  1. 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...

  2. Effect of verapamil and lidocaine on TRPM and NaV1.9 gene expressions in renal ischemia-reperfusion.

    Science.gov (United States)

    Dusmez, D; Cengiz, B; Yumrutas, O; Demir, T; Oztuzcu, S; Demiryurek, S; Tutar, E; Bayraktar, R; Bulut, A; Simsek, H; Daglı, S Nur; Kılıc, T; Bagcı, C

    2014-01-01

    To determine effects on calcium and sodium channels of Ca(2+) and Na(+) channel blockers in the present study, expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, and NaV1.9 genes were evaluated in kidney tissues after induced ischemia-reperfusion. Forty albino Wistar male rats were equally divided into 4 groups as follows: group I: control group (n = 10), group II: ischemia group (60 minutes of ischemia + 48 hours of reperfusion; n = 10), group III: ischemia (60 minutes of ischemia + 48 hours of reperfusion) + calcium channel blocker (n = 8), group IV: ischemia (60 minutes of ischemia + 48 hours of reperfusion) + sodium channel blocker (n = 8). When compared to ischemia group expression levels of TRPM2, TRPM4, TRPM6, and NaV1.9 in Ca(2+) and Na(+) channel blocker groups were increased, whereas that of TRPM7 was decreased. However, expression levels of TRPM1, TRPM3, TRPM5, and TRPM8 were not determined in kidney tissue. Histologically, the Ca(2+) channel blocker verapamil and the Na(+) channel blocker lidocaine inhibited the cell death in kidney tissue compared to control. Our study suggested that verapamil and lidocaine significantly reduce the degree of ischemia-reperfusion injury due to effects to TRPM and Nav1.9 genes. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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

    Serum verapamil and metabolite concentrations were determined by HPLC in 29 patients in routine treatment with verapamil, and 23 were in steady state. Dosage levels and corresponding mean trough levels (+/- S.D.) were as follows: 120 mg daily: 79.1 (+/- 77) nmol/l, 240 mg daily: 173.3 (+/- 200.......1) nmol/l, 360 mg daily: 204 (+/- 110.2) nmol/l and 480 mg daily: 361.0 (+/- 231.4) nmol/l. The variation coefficients were 97.3, 115.4, 54.0, and 62.1, respectively, thus showing considerable interpatient variation. Repeated determination of trough levels showed, in contrast, only small intrapatient...

  5. [Successful treatment by 4--aminopyridine of three cases of severe verapamil poisoning].

    Science.gov (United States)

    Magdalan, Jan; Kochman, Krystyna; Antończyk, Andrzej; Przewłocki, Michal; Smolarek, Małgorzata

    2003-01-01

    Three cases of verapamil intoxication were presented. In all cases shock and circulatory insufficiency were observed. In case no. 1 respiratory insufficiency and confusion were observed, in case no. 3 second-degree atrioventricular block was noted. The protracted hypotension (shock), circulatory insufficiency and atrioventricular block did not respond to calcium therapy, high dose of vasopressor amines and atropine. The addition of 4-aminopyridine (4-AP) infusion resulted in fast receding of poisoning symptoms; receding of atrioventricular block, cardiogenic shock and circulatory insufficiency. These cases suggest the usefulness of 4-AP in the treatment of verapamil poisoning. However, confirmation of the effectiveness of this substance for pharmacotherapy of calcium antagonists poisoning requires further clinical research. The influence of 4-AP on calcium channels is indirect. It blocks potassium channels K1 in cytoplasm side which makes potassium to stay inside the cell leading to depolarisation and opening of voltage-dependent calcium channels.

  6. 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.

  7. Effect of Verapamil as an Adjuvant to Levobupivacaine in Supraclavicular Brachial Plexus Block.

    Science.gov (United States)

    Routray, Sidharth Sraban; Mishra, Debasis; Routray, Daityari; Nanda, Kasturi

    2017-01-01

    Many adjuvants have been used with local anesthetics to reduce the time of onset and prolong the duration of analgesia in brachial plexus blocks. However, few studies are there using verapamil as an adjuvant with levobupivacaine. This study aims to study the effects of verapamil as adjuvant to levobupivacaine in supraclavicular block for upper extremity surgery. In this double-blinded clinical trial, 60 American Society of Anesthesiologist Class I and II patients posted to undergo upper extremity surgery were divided into 2 different groups randomly. In Group A, the patients received 30 ml levobupivacaine 0.5% plus 2 ml normal saline and Group B patients received 30 ml levobupivacaine 0.5% plus 5 mg verapamil diluted to 2 ml normal saline for supraclavicular block. Time of request for rescue analgesia, onset and duration of sensory motor blocks and changes in hemodynamic parameters were studied and analyzed. P < 0.001 was considered statistically significant. Time for a request for rescue analgesia was 425.80 ± 90.46 min in Group B and 366.13 ± 70.42 min in Group A which was clinically significant. The mean of sensory and motor block onset time in Group B was less than in Group A, the difference between the two groups being statistically significant (P < 0.001). In Group A, mean duration of sensory block was 316.13 ± 91.08 min and in Group B was 375.83 ± 114.48 min, which was statistically significant (P < 0.001). The addition of verapamil as an adjuvant to levobupivacaine in brachial plexus blockade delayed the requirement of rescue analgesia with decreased onset time and prolonged duration of sensory and motor block characteristics.

  8. PAINLESS RADIAL ACCESS PROCEDURES WITH NICORANDIL: A COMPARATIVE ASSESSMENT WITH CONVENTIONAL VERAPAMIL - NITROGLYCERINE COCKTAIL

    Directory of Open Access Journals (Sweden)

    Jain T Kallarakkal

    2012-11-01

    Full Text Available Background: Radial artery spasm is a major limitation of the transradial approach. This study was designed to compare the spasmolytic effect between nicorandil and the conventional cocktail of nitroglycerine and verapamil during transradial coronary procedures. Materials and methods: 200 patients were randomized into two groups to compare 8 mg of nicorandil and cocktail (mixture of normal saline, 5 mg of verapamil and 200 μg of nitroglycerin. Radial artery spasm and patient comfort in both the groups were assessed. Results: Radial artery spasm and conversion rate to femoral access were statistically insignificant comparing both groups. None of the patients in the Nicorandil group had pain or burning sensation during its administration whereas all patients who received cocktail had pain and burning sensation in spite of aspirating blood and mixing cocktail thoroughly with blood. Conclusions: Nicorandil is a superior vasodilator and can be considered as a better alternative to the conventional cocktail of nitroglycerine and verapamil without any adverse effects as it gives more comfort to the patient by avoiding pain and burning sensation during its administration

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

    Science.gov (United States)

    Kunte, S.; Tandale, P.

    2010-01-01

    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 PMID:21180465

  10. Experimentally induced helper dispersal in colonially breeding cooperative cichlids

    NARCIS (Netherlands)

    Heg, D.; Heg-Bachar, Z.; Brouwer, L.; Taborsky, M.

    2008-01-01

    The 'benefits of philopatry' hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the

  11. carpal arthrodesis for the management of experimentally induced ...

    African Journals Online (AJOL)

    INDUCED RADIAL NERVE PARALYSIS IN DOGS. HASSAN', A.Z. ... desensitization. Three weeks post surgery, three animals in the control group showed ... voluntary motor and reflex abnormalities are often ... paralysis following injury due to.

  12. Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy: a pilot study.

    Science.gov (United States)

    Nicita, Francesco; Spalice, Alberto; Papetti, Laura; Nikanorova, Marina; Iannetti, Paola; Parisi, Pasquale

    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. Seven children with drug-resistant structural-metabolic, unknown or genetic (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of 1mg/kg/day and titrated up to 1.5mg/kg/day. After completing the titration period, patients entered a 14-month maintenance period and were followed up at 3, 8, and 14 months. Heart monitoring was performed at baseline and at each follow-up. The primary outcome measure was the response of seizures to verapamil. Three subjects with genetically determined DS showed a partial (reduction of 50-99%) response for all types of seizures. A patient with DS without known mutation showed a partial control of all types of seizures in the first 13 months; then seizures worsened and verapamil was suspended. Two patients with structural epilepsy and one with Lennox-Gastaut syndrome showed no improvement. Any side effects were recorded. Add-on treatment with verapamil seems to have some effect in controlling seizures in patients with genetically determined DS. Our observations justify further research on the relationship between calcium channels, calcium channel blockers, and channelopathies. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

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

    2007-01-01

    regimen with saline only. All rats were killed 7 days after MCAO. Infarct volume was quantified stereologically. The mean body temperature (35.6 + 1.0 degrees C) during 24 hours after bolus injection of Talipexole was significantly lower than in control rats (37.3 +/- 0.5 degrees C), P ... 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...... 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...

  14. Summer mastitis experimentally induced by Hydrotaea irritans exposed to bacteria

    NARCIS (Netherlands)

    Chirico, J.; Jonsson, P.; Kjellberg, S.; Thomas, G.

    1997-01-01

    Summer mastitis is an acute suppurative bacterial infection of the udder in heifers and dry cows. To ascertain the possible role of flies in the transmission of the disease, experimental exposures of recipient heifers to Hydrotaea irritans previously exposed to bacteria were carried out. Flies were

  15. Experimental observation of direct current voltage-induced phase ...

    Indian Academy of Sciences (India)

    The dynamics of two uncoupled distinct Chua circuits driven by a common direct current voltage is explored experimentally. It was found that, with increasing current intensity, the dominant frequencies of these two Chua circuits will first vary at different speeds, approach an identical value for a certain current intensity and ...

  16. Reversal of experimental varicocele-induced testicular toxicity by L ...

    African Journals Online (AJOL)

    testicular volumes, caudal epididymal sperm characteristics, testicular histology and serum hormone levels were evaluated. Results showed that the testes of the rats that were given vitamin C post experimental varicocele had better physiological, biochemical and histological profiles than those of the untreated animals.

  17. Pharmacokinetic changes of halofantrine in experimentally-induced ...

    African Journals Online (AJOL)

    It was hypothesized in this study that alterations in plasma lipoprotein profile and disturbed gastrointestinal motility as observed in diabetes mellitus may influence the disposition of halofantrine (HF), a highly lipophilic antimalarial drug. Therefore, using a rat model of diabetes mellitus induced by administration of alloxan ...

  18. Influence of physical restraint on the onset of experimentally induced ...

    African Journals Online (AJOL)

    The role of intermittent repeated physical restraint on the onset of diabetes mellitus (DM) was in-vestigated in this study. The study compared the onset of DM in mice dosed with streptozotocin (STZ), a DM-inducing drug, with immediate subsequent exposure to either physical restraint stress or non- exposure to the stress.

  19. Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy; Evaluation by exercise [sup 201]Tl SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yoko; Sugihara, Hiroki; Ootsuki, Katsuichi (Kyoto Prefectural Univ. of Medicine (Japan)) (and others)

    1993-01-01

    Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial [sup 201]Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient [sup 201]Tl perfusion defects under control conditions. [sup 201]Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient dilation index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p<0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of these revealed improvements of TDI and 7 of the 10 disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p<0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM. (author).

  20. Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury

    Science.gov (United States)

    Wang, Zheng; Guo, Qiong-Ya; Zhang, Xiao-Ju; Li, Xiao; Li, Wen-Ting; Ma, Xi-Tao; Ma, Li-Jun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1β, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-β1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-β1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis. PMID:24886817

  1. 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.

  2. 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.

  3. A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis.

    Science.gov (United States)

    Rombeau, J L

    1990-01-01

    Studies in animal models of enterocolitis have failed to confirm the purported metabolic and functional benefits of bowel rest induced by use of an elemental diet. Recent reports have demonstrated that glutamine-supplemented diets ameliorate or reverse many of the adverse effects of experimentally induced enterocolitis. Human studies are needed to confirm these findings.

  4. Requirement for Tumor Necrosis Factor Receptor 2 Expression on Vascular Cells To Induce Experimental Cerebral Malaria

    OpenAIRE

    Stoelcker, Benjamin; Hehlgans, Thomas; Weigl, Karin; Bluethmann, Horst; Grau, Georges E.; Männel, Daniela N.

    2002-01-01

    Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria.

  5. [Fetal experimentation, transplantations, cosmetics and their connection with induced abortion].

    Science.gov (United States)

    Redondo Calderón, José Luis

    2012-01-01

    The increase in induced abortion produces large numbers of cells, tissues and organs, which are used in several fields of Medicine, either in research or in treatment. The main uses are in Cardiology, Hematology, Metabolism, Embryology, Neurology, Immunology, Ophthalmology, Dermatology and Transplantations. Flavor enhancers and cosmetics also benefit. Utilitarianism has led to an increase in abortion-originated cell and tissue banks. Abortion is justified through the manipulation of language. Vested interests give rise to complicity in researchers and society as a whole. Abortion and tissue 'donation' cannot be split; since fresh tissues are involved there is a symbiotic relationship between them. Valid consent is not possible. A contradiction emerges, the nasciturus is not desired or valued but fetal organs are. When someone is deprived of his rights it is because another wants to enslave them. Research must have a moral base. Knowledge should not be increased at any price. Something that is legal and well intentioned is not always morally acceptable. The duty of omission is applicable. Means to achieve a goal must be ethical means. Educational efforts to restore respect for the human embryo and fetus must be promoted. Technical advances are not always in accordance with human nature and dignity. Research and treatment that do not resort to cells, tissues and organs obtained from induced abortions should be promoted.

  6. Effect of menthol in experimentally induced ulcers: pathways of gastroprotection.

    Science.gov (United States)

    Rozza, A L; Hiruma-Lima, C A; Takahira, R K; Padovani, C R; Pellizzon, C H

    2013-11-25

    Based on ethnopharmacological indications that Mentha species may be used in the treatment of gastrointestinal diseases, this study aimed to characterize the gastroprotective mechanisms of menthol (ME), the major compound of the essential oil from species of the genus Mentha. The gastroprotective action of ME was analyzed in gastric ulcers that were induced by ethanol or indomethacin in Wistar male rats. The mechanisms responsible for the gastroprotective effect were assessed by analyzing the amount of mucus secreted, involvement of non-protein sulfhydryl (NP-SH) compounds, involvement of calcium ion channels and NO/cGMP/K(+)ATP pathway, gastric antisecretory activity and the prostaglandin E2 (PGE2) production. The anti-diarrheal activity and acute toxicity of ME were also evaluated. Oral treatment with ME (50mg/kg) offered 88.62% and 72.62% of gastroprotection against ethanol and indomethacin, respectively. There was an increased amount of mucus and PGE2 production. The gastroprotective activity of ME involved NP-SH compounds and the stimulation of K(+)ATP channels, but not the activation of calcium ion channels or the production of NO. The oral administration of ME induced an antisecretory effect as it decreased the H(+) concentration in gastric juice. ME displayed anti-diarrheal and antiperistaltic activity. There were no signs of toxicity in the biochemical analyses performed in the rats' serum. These results demonstrated that ME provides gastroprotective and anti-diarrheal activities with no toxicity in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Ecotoxocological effects of short-term exposure to a human pharmaceutical Verapamil in juvenile rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Randak, Tomas

    2010-09-01

    Verapamil (VRP) is a calcium channel blocker that is a highly prescribed compound and commonly present in aquatic environment, but the ecotoxicological effects of this pharmaceutical in fish have not been fully documented. In this study, the toxic effects of VRP were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute static bioassay. In the acute test, the median lethal concentration (LC50, 2.72 mg/L) was evaluated and the behavioral changes were obviously intensified with increasing VRP concentrations. Compared to the control, oxidative stress was observed in fish tissues with different levels after short-term exposure to sublethal concentrations (0.27 and 1.35 mg/L) of VRP. Activities of SOD and GPx in fish brain were induced at 0.27 mg/L VRP, but all the antioxidant enzymes (SOD, GPx and GR) in fish brain were decreased at 1.35 mg/L VRP. When compared to the control, all the antioxidant enzymes in gill were decreased in both treated groups, but there was no significant change in muscle. Additional, muscle DNA/RNA ratio in fish exposed at 1.35 mg/L VRP was significantly lower than that in the control. Furthermore, through chemometrics of all parameters measured in fish exposed to sublethal VRP concentrations using principal component analysis, two groups with 89.8% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in of fish indicated that VRP-induced environmental stress; but according to VRP residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  8. Effect of duration of exposure to verapamil on vincristine activity against multidrug-resistant human leukemic cell lines.

    Science.gov (United States)

    Cass, C E; Janowska-Wieczorek, A; Lynch, M A; Sheinin, H; Hindenburg, A A; Beck, W T

    1989-11-01

    Verapamil sensitizes multidrug-resistant cell lines to various heterocyclic anticancer drugs by inhibition of energy-dependent release of drug, presumably by interaction with membrane glycoproteins involved in drug efflux. This work assessed verapamil sensitization of human multidrug-resistant lymphocytic and myeloid leukemic cell lines (CEM/VLB100, HL-60/AR) to vincristine during exposures of short duration (4 h). When cells were transferred to drug-free medium immediately after simultaneous 4-h exposures to vincristine and verapamil, the antiproliferative activity of vincristine was not altered in CEM/VLB100 cells and was only moderately increased in HL-60/AR cells. In contrast, when cells were transferred to verapamil-containing medium, vincristine activity was greatly increased against both CEM/VLB100 and HL-60/AR cells. Verapamil enhanced accumulation and inhibited release of [3H]vincristine by CEM/VLB100 and HL-60/AR cells, indicating that the sensitization was due to an increase in cell-associated vincristine after transfer of cells to vincristine-free medium. Slot blot analysis of cellular RNA with the pMDR1 probe revealed high levels of expression of the mdr1 gene in CEM/VLB100 cells but no detectable expression in HL-60/AR cells. Consistent with this finding, polypeptides (Mr 170,000 to 180,000) that were recognized by a monoclonal antibody (C219) against P-glycoprotein were greatly overexpressed in CEM/VLB100 cells, but were expressed at low levels, if at all, in HL-60/AR cells. These results demonstrate the importance of duration of exposure to verapamil in reversing multidrug resistance, not only in cells that overexpress P-glycoprotein but also in cells, such as HL-60/AR, that express little, if any, P-glycoprotein.

  9. Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study.

    Science.gov (United States)

    Mehta, Rashmi; Kelleher, Dennis; Preece, Andrew; Hughes, Stephen; Crater, Glenn

    2013-01-01

    The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting β₂ agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4) inhibitor frequently used by patients with COPD and cardiovascular comorbidities. Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 μg or UMEC 500 μg/VI 25 μg. All subjects received a single tablet containing 240 mg verapamil on each of days 9-13. Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated. There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone. UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold) was observed with verapamil. Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination. Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug. The UMEC/VI combination is unlikely to have a clinically meaningful drug-drug interaction with moderate P-glycoprotein transporter and CYP3A4 inhibitor drugs.

  10. Experimental Evidence of Boundary Induced Coupling Currents in LHC Prototypes

    CERN Document Server

    Bottura, L; Ang, Z

    1996-01-01

    The field quality of 10 m long LHC dipole models has been measured with short rotating coils to explore its dependence on time and position. Multipoles exhibit a longitudinal periodic variation, with period equal to the twist pitch length. This periodicity is shown here to have at least two components with very different time constants. The amplitude of the component with the shorter time constant, in the range of 100 to 300 s, depends on position and time. Larger amplitudes are measured at early times after a ramp and close to regions with incomplete cable transposition with respect to the non-uniform external field change. As the multipoles periodicity is due to current imbalance in the cables, we attribute the short time scale variations to the presence of space and time decaying boundary induced coupling currents (BICC's) in the cable. An estimate of their value is given

  11. Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

    Science.gov (United States)

    Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

    2013-11-01

    Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.

  12. Alleviating effects of morin against experimentally-induced diabetic osteopenia

    Directory of Open Access Journals (Sweden)

    Abuohashish Hatem M

    2013-02-01

    Full Text Available Abstract Background Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone, a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats. Methods Streptozotocin (STZ-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD, osteocalcin (OC, bone specific alkaline phosphatase (BALP, telopeptides of collagen type I (CTX, interleukin 1 beta (IL-1β, interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD and other morphometric parameters. Results Significant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment. Conclusion These findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti

  13. Compartment syndrome–induced microvascular dysfunction: an experimental rodent model

    Science.gov (United States)

    Lawendy, Abdel-Rahman; Sanders, David W.; Bihari, Aurelia; Parry, Neil; Gray, Daryl; Badhwar, Amit

    2011-01-01

    Background Acute compartment syndrome (CS) is a limb-threatening disease that results from increased intracompartmental pressure. The pathophysiologic mechanisms by which this occurs are poorly understood. This study was designed to measure the effects of increased intracompartmental pressure on skeletal muscle microcirculation, inflammation and cellular injury using intravital videomicroscopy (IVVM) in a clinically relevant small animal model. Methods We induced CS in 10 male Wistar rats (175–250 g), using a saline infusion technique. Intracompartmental pressure was controlled between 30 and 40 mm Hg and maintained for 45 minutes. After fasciotomy, the extensor digitorum longus muscle was visualized using IVVM, and perfusion was quantified. We quantified leukocyte recruitment to measure the inflammatory response. We measured muscle cellular injury using a differential fluorescent staining technique. Results The number of nonperfused capillaries increased from 12.7 (standard error of the mean [SEM] 1.4 ) per mm in the control group to 30.0 (SEM 6.7) per mm following 45 minutes of elevated intracompartmental pressure (CS group; p = 0.031). The mean number of continuously perfused capillaries (and SEM) decreased from 78.4 (3.2) per mm in the control group to 41.4 (6.9) per mm in the CS group (p = 0.001). The proportion of injured cells increased from 5.0% (SEM 2.1%) in the control group to 16.3% (SEM 6.8%) in the CS group (p = 0.006). The mean number of activated leukocytes increased from 3.6 (SEM 0.7) per 100 μm2 in the control group to 8.6 (SEM 1.8) per 100 μm2 in the CS group (p = 0.033). Conclusion Early CS-induced microvascular dysfunction resulted in a decrease in nutritive capillary perfusion and an increase in cellular injury and was associated with a severe acute inflammatory component. PMID:21443836

  14. Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

    Science.gov (United States)

    Mohiti-Asli, M; Ghanaatparast-Rashti, M

    2015-06-15

    An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

    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...

  16. 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.

  17. Experimental Investigation of Cavitation Induced Feedline Instability from an Orifice

    Science.gov (United States)

    Hitt, Matthew A.; Lineberry, David M.; Ahuja, Vineet; Frederick, Robert A,

    2012-01-01

    This paper details the results of an experimental investigation into the cavitation instabilities created by a circular orifice conducted at the University of Alabama in Huntsville Propulsion Research Center. This experiment was conducted in concert with a computational simulation to serve as a reference point for the simulation. Testing was conducted using liquid nitrogen as a cryogenic propellant simulant. A 1.06 cm diameter thin orifice with a rounded inlet was tested in an approximately 1.25 kg/s flow with inlet pressures ranging from 504.1 kPa to 829.3 kPa. Pressure fluctuations generated by the orifice were measured using a high frequency pressure sensor located 0.64 tube diameters downstream of the orifice. Fast Fourier Transforms were performed on the high frequency data to determine the instability frequency. Shedding resulted in a primary frequency with a cavitation related subharmonic frequency. For this experiment, the cavitation instability ranged from 153 Hz to 275 Hz. Additionally, the strength of the cavitation occur red as a function of cavitation number. At lower cavitation numbers, the strength of the cavitation instability ranged from 2.4 % to 7 % of the inlet pressure. However, at higher cavitation numbers, the strength of the cavitation instability ranged from 0.6 % to 1 % of the inlet pressure.

  18. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    Science.gov (United States)

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-09-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  19. Toxin-Induced Experimental Models of Learning and Memory Impairment

    Directory of Open Access Journals (Sweden)

    Sandeep Vasant More

    2016-09-01

    Full Text Available Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson’s disease dementia and Alzheimer’s disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  20. Health status, mood, and cognition in experimentally induced subclinical thyrotoxicosis.

    Science.gov (United States)

    Samuels, M H; Schuff, K G; Carlson, N E; Carello, P; Janowsky, J S

    2008-05-01

    Our objective was to determine whether subclinical thyrotoxicosis alters health status, mood, and/or cognitive function. This was a double-blinded, randomized, cross-over study of usual dose l-T(4) (euthyroid arm) vs. higher dose l-T(4) (subclinical thyrotoxicosis arm) in hypothyroid subjects. A total of 33 hypothyroid subjects receiving l-T(4) were included in the study. Subjects underwent measurements of health status, mood, and cognition: Short Form 36 (SF-36); Profile of Mood States (POMS); and tests of declarative memory (Paragraph Recall, Complex Figure), working memory (N-Back, Subject Ordered Pointing, and Digit Span Backwards), and motor learning (Pursuit Rotor). These were repeated after 12 wk on each of the study arms. Mean TSH levels decreased from 2.15 to 0.17 mU/liter on the subclinical thyrotoxicosis arm (P learning was better during the subclinical thyrotoxicosis arm, whereas declarative and working memory measures did not change. This improvement was related to changes in the SF-36 physical component summary and POMS tension subscales and free T(3) levels. We found slightly impaired physical health status but improvements in measures of mental health and mood in l-T(4) treated hypothyroid subjects when subclinical thyrotoxicosis was induced in a blinded, randomized fashion. Motor learning was also improved. These findings suggest that thyroid hormone directly affects brain areas responsible for affect and motor function.

  1. Serum protein concentrations in calves with experimentally induced pneumonic pasteurellosis

    Directory of Open Access Journals (Sweden)

    Fagliari J.J.

    2003-01-01

    Full Text Available Ten healthy 2 to 4-week-old Holstein calves were randomly allotted into control and infected groups. Control calves (n=5 were inoculated intrabronchially with 5ml of Dulbecco's phosphate-buffered saline solution (DPBSS. Infected calves (n=5 were inoculated intrabronchially with 5x10(9 log-phase Mannheimia haemolytica organisms suspended in 5ml of DPBSS. Blood samples were obtained 15 minutes before and one, two, four and six hours after inoculation. Serum protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Serum concentrations of proteins with molecular weights of 125,000 D (ceruloplasmin, 60,000 D (a 1-antitrypsin, 45,000 D (haptoglobin, and 40,000 D (acid glycoprotein were significantly increased in calves with pneumonic pasteurellosis, compared with concentrations in control calves. Results indicate that acute phase proteins increase more rapidly after the onset of inflammation than previously thought. Measurement of serum protein concentrations may be useful in monitoring the progression of the induced pneumonic pasteurellosis in calves.

  2. Experimental Optic Neuritis Induced by a Demyelinating Strain of Mouse Hepatitis Virus▿

    Science.gov (United States)

    Shindler, Kenneth S.; Kenyon, Lawrence C.; Dutt, Mahasweta; Hingley, Susan T.; Sarma, Jayasri Das

    2008-01-01

    Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting mixed inflammatory cell infiltration. In contrast, MHV-2, a nondemyelinating MHV strain, does not induce ON. Results reveal a reproducible virus-induced ON model important for the evaluation of novel therapies. PMID:18579591

  3. Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2014-12-01

    Full Text Available Objective: To evaluate the influence of environmental enrichment (EE on memory, cytokines, and brain-derived neurotrophic factor (BDNF in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood. EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

  4. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    Science.gov (United States)

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. © International & American

  5. Experimental particle acceleration by water evaporation induced by shock waves

    Science.gov (United States)

    Scolamacchia, T.; Alatorre Ibarguengoitia, M.; Scheu, B.; Dingwell, D. B.; Cimarelli, C.

    2010-12-01

    Shock waves are commonly generated during volcanic eruptions. They induce sudden changes in pressure and temperature causing phase changes. Nevertheless, their effects on flowfield properties are not well understood. Here we investigate the role of gas expansion generated by shock wave propagation in the acceleration of ash particles. We used a shock tube facility consisting of a high-pressure (HP) steel autoclave (450 mm long, 28 mm in internal diameter), pressurized with Ar gas, and a low-pressure tank at atmospheric conditions (LP). A copper diaphragm separated the HP autoclave from a 180 mm tube (PVC or acrylic glass) at ambient P, with the same internal diameter of the HP reservoir. Around the tube, a 30 cm-high acrylic glass cylinder, with the same section of the LP tank (40 cm), allowed the observation of the processes occurring downstream from the nozzle throat, and was large enough to act as an unconfined volume in which the initial diffracting shock and gas jet expand. All experiments were performed at Pres/Pamb ratios of 150:1. Two ambient conditions were used: dry air and air saturated with steam. Carbon fibers and glass spheres in a size range between 150 and 210 μm, were placed on a metal wire at the exit of the PVC tube. The sudden decompression of the Ar gas, due to the failure of the diaphragm, generated an initial air shock wave. A high-speed camera recorded the processes between the first 100 μsec and several ms after the diaphragm failure at frame rates ranging between 30,000 and 50,000 fps. In the experiments with ambient air saturated with steam, the high-speed camera allowed to visualize the condensation front associated with the initial air shock; a maximum velocity of 788 m/s was recorded, which decreases to 524 m/s at distance of 0.5 ±0.2 cm, 1.1 ms after the diaphragm rupture. The condensation front preceded the Ar jet front exhausting from the reservoir, by 0.2-0.5 ms. In all experiments particles velocities following the initial

  6. An experimental study on renal damage induced by melamine cyanurate

    Directory of Open Access Journals (Sweden)

    Guan-tian YU

    2011-10-01

    Full Text Available Objective To explore the nephrotoxicity of melamine cyanurate in SD rats.Methods Ninety SPF SD rats were randomly assigned into 3 groups(30 each according to the doses of melamine cyanurate they received(0,200,400mg/kg,which were repectively given daily by gavage for 60 consecutive days.Six rats in each group were confined in metabolism cages for the first week,and urine samples were collected over a 24h period.Before drug administration,the blood samples and kidney pathology were evaluated in 6 rats of each group on day 4,14,31,45 and 60 to determine serum creatinine,blood urea nitrogen(BUN,serum uric acid and serum cystatin C.Results The urine volume of rats was significantly higher in 200mg/kg group than in normal controls(P < 0.05,while no statistical difference was found between 400mg/kg and control group.After administration of melamine cyanurate,the levels that of serum cystatin C increased significantly,while that of serum uric acid decreased markedly,as compared with the control group(P < 0.05.Significantly higher levels of BUN,serum cystatin C and creatinine were found in 200 mg/kg group(30-60 days and 400mg/kg group(4th day compared with that of control group(P < 0.01.On the 2nd day,specific crystals were found in the urinary sediment smears of melamine cyanurate group.The pathological changes in kidney included yellow discoloration and edema of the organ in 200mg/kg group(since 31st day and 400mg/kg group(since 4th day.Examination of pathological sections showed that there was deposition of a number of yellow,semi-transparent and concentric round crystals in renal tubules.Conclusions Administration of melamine cyanurate by gavage may induce crystal formation and cause renal dysfunction.Meanwhile,melamine cyanurate may have some diuretic function,thereby influence the metabolism and decrease the concentration of uric acid in blood.

  7. Mortality of patients excluded from the Danish Verapamil Infarction Trail II. The DAVIT-II Study Group

    DEFF Research Database (Denmark)

    Madsen, J K; Hansen, J F

    1993-01-01

    The 18 month mortality rate in 2180 patients excluded from the Danish Verapamil Infarction Trail II (DAVIT II) was 25.6%. In non-consenters (n = 368) this was 15.0% compared with 13.85 in 897 placebo-treated patients (hazard ratio 1.09 [P = 0.60] when adjusting for sex and age). The increased...

  8. Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study

    Directory of Open Access Journals (Sweden)

    Mehta R

    2013-03-01

    Full Text Available Rashmi Mehta,1 Dennis Kelleher,1 Andrew Preece,2 Stephen Hughes,3 Glenn Crater4 1Respiratory Medicines Development Center, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Respiratory Medicines Development Center, GlaxoSmithKline, Stockley Park West, UK; 3GlaxoSmithKline R&D, Bioanalytical Sciences and Toxicokinetics, Drug Metabolism and Pharmacokinetics, Ware, UK; 4Respiratory Medicine Development Center, GlaxoSmithKline, Mississauga, ON, Canada Background: The combination of umeclidinium (UMEC, a long-acting muscarinic receptor antagonist, and vilanterol (VI, a selective long-acting ß2 agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4 inhibitor frequently used by patients with COPD and cardiovascular comorbidities. Methods: Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 µg or UMEC 500 µg/VI 25 µg. All subjects received a single tablet containing 240 mg verapamil on each of days 9–13. Results: Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated. There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone. UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold was observed with verapamil. Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination. Conclusion: Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug. The UMEC/VI combination is unlikely to have a clinically meaningful drug

  9. Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine.

    Science.gov (United States)

    Pearigen, P D; Benowitz, N L

    1991-01-01

    The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients

  10. Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

    Science.gov (United States)

    Zabrodin, O. N.

    1980-01-01

    The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration.

  11. 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.

  12. Spectrophotometric determination of verapamil hydrochloride in drug formulations with chloramine-T as oxidant.

    Science.gov (United States)

    Rahman, Nafisur; Hoda, Md Nasrul

    2002-10-01

    A new spectrophotometric method is described for the determination of verapamil hydrochloride, based on its oxidation with chloramine-T in hydrochloric acid medium. It produces a yellow colored compound with maximum absorbance at 425 nm. Beer's law was obeyed in the concentration range 0-340 micro g mL(-1) with molar absorptivity 2 x 10(3) L mol(-1) cm(-1) and RSD 0.3-0.82%. All variables were studied to optimize the reaction conditions. No interferences were observed from the common excipients present in the formulations. The method has been applied successfully to the determination of the drug in pharmaceutical preparations. Statistical comparison of the results with those from the reference method reveals excellent agreement and confirms that accuracy and precision are not significantly different.

  13. Histometric assessment of the effect of diabetes mellitus on experimentally induced periodontitis in rats.

    Science.gov (United States)

    Pepelassi, Eudoxie; Xynogala, Ioanna; Perrea, Despina; Agrogiannis, George; Pantopoulou, Alkistis; Patsouris, Efstratios; Vrotsos, Ioannis

    2012-04-01

    The aim of this interventional animal study was to assess histologically the effect of experimental diabetes in rats with experimental periodontitis in terms of alveolar bone loss and the effect of experimental periodontitis on glucose levels in diabetes. Forty-seven Wistar rats were studied: 12 healthy controls (C), 10 with experimental diabetes (D), 12 with experimental diabetes and experimental periodontitis (DP) and 13 with experimental periodontitis (P). Diabetes was induced by streptozotocin injection and periodontitis was induced at the right second maxillary molar by ligation. Serum glucose levels were measured at specific time points. Sixty-one days after ligation, the rats were sacrificed. Histometric analysis assessed alveolar crest level. For ligated groups, alveolar bone loss was expressed as the difference in alveolar crest level between right and left maxillary molars. Diabetes alone did not statistically significantly affect alveolar crest level. The combination of diabetes and periodontitis caused greater alveolar bone loss (946.1 +/- 719.9 microm) than periodontitis alone (639.7 +/- 294.2 microm); however, the difference did not reach statistical significance. Periodontitis did not significantly increase glucose levels in diabetic rats. The average glucose levels were 545.4 (499 - 563) and 504.5 (445 - 560) mg/dL for diabetic and diabetic ligated rats, respectively. Within its limits, this study demonstrated that the severity of alveolar bone loss in periodontitis was not significantly aggravated by diabetes and the serum glucose levels in diabetes were not affected by periodontitis.

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

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    Alexandru D P Papoiu

    Full Text Available BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  15. Experimentally induced stress in rheumatoid arthritis of recent onset: effects on peripheral blood lymphocytes

    NARCIS (Netherlands)

    Geenen, R.; Godaert, G. L.; Heijnen, C. J.; Vianen, M. E.; Wenting, M. J.; Nederhoff, M. G.; Bijlsma, J. W.

    1998-01-01

    To examine the effects of experimentally-induced stress on the mobilization of peripheral blood lymphocytes (PBL) in patients with rheumatoid arthritis (RA) of recent onset. Twenty-two (16 F, 6 M) patients (mean age 57.6 yrs.) and 23 (15 F, 8 M) healthy subjects (mean age 54.7 yrs.) were subjected

  16. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Tran, E H; Hardin-Pouzet, H; Verge, G

    1997-01-01

    Nitric oxide (NO), produced by inducible NO synthase (iNOS), may play a role in inflammatory demyelinating diseases of the central nervous system (CNS). We show upregulation of iNOS mRNA in CNS of SJL/J mice with experimental allergic encephalomyelitis (EAE). Using antibodies against mouse i...

  17. Diet shifts and population dynamics of estuarine foraminifera during ecosystem recovery after experimentally induced hypoxia crises

    NARCIS (Netherlands)

    Brouwer, G.M.; Duijnstee, Ivo; Hazeleger, J.H.; Rossi, F.; Lourens, L.J.; Middelburg, J.J.; Wolthers, M.

    2016-01-01

    This study shows foraminiferal dynamics after experimentally induced hypoxia within the wider context of ecosystem recovery. 13C-labeled bicarbonate and glucose were added to the sediments to examine foraminiferal diet shifts during ecosystem recovery and test-size measurements were used to deduce

  18. An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

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    Mallia Patrick

    2006-09-01

    Full Text Available Abstract Background Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. Methods We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II. Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. Results All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events. Conclusion Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.

  19. 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)

  20. Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Zehntner, Simone P; Bourbonniere, Lyne; Hassan-Zahraee, Mina

    2004-01-01

    The role of nitric oxide (NO) in central nervous system (CNS) inflammation is uncertain. Whereas experimental autoimmune encephalomyelitis (EAE) is exacerbated in mice deficient in inducible nitric oxide synthase (iNOS), inhibitor studies have suggested a pro-inflammatory role for NO. These discr...

  1. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    Science.gov (United States)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  2. 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.

  3. 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.

  4. Change in QRS morphology as a marker of spontaneous elimination in verapamil-sensitive idiopathic left ventricular tachycardia.

    Science.gov (United States)

    Kawakami, Hiroshi; Aiba, Takeshi; Ishibashi, Kohei; Nakajima, Ikutaro; Wada, Mitsuru; Kamakura, Tsukasa; Inoue, Yuko; Miyamoto, Koji; Okamura, Hideo; Nagase, Satoshi; Noda, Takashi; Kokubo, Yoshihiro; Miyamoto, Yoshihiro; Yasuda, Satoshi; Kamakura, Shiro; Kusano, Kengo

    2017-12-11

    Verapamil-sensitive idiopathic left ventricular tachycardia (verapamil-ILVT) is thought to be due to a reentry within the LV fascicular system. Radiofrequency catheter ablation (RFCA) is effective for elimination of the VT; however, a long-term prognosis of patients with verapamil-ILVT is still unclear. Eighty consecutive verapamil-ILVT patients (62 men, 31 ± 12 years of age, LVEF: 65 ± 4%) were enrolled. Seventy-six (95%) cases of VT involved right bundle branch block and left axis deviation. We retrospectively analyzed changes in the QRS duration (ΔQRS-d) and QRS axis (ΔQRS-axis) during follow-up and compared them with recurrence of VT. During a mean follow-up period of 10 years (2-32 years), no sudden death or heart failure occurred. Fifty-one (64%) patients underwent RFCA, and 46 (90%) of them had no VT without any medication after RFCA. The ΔQRS-d (16 ± 2 vs. 8 ± 1 ms, P = 0.24) and ΔQRS-axis (20 ± 4 vs. 4 ± 3 degrees, P = 0.23) were not different in patients with no VT (VT[-]) and those with recurrence of VT (VT[+]). However, in the remaining 29 patients without RFCA, VT was spontaneously eliminated in 16 patients. The ΔQRS-d (30 ± 6 vs. 6 ± 1 ms, P = 0.002) and ΔQRS-axis (23 ± 4 vs. 5 ± 2 degrees, P = 0.001) were significantly larger in VT(-) patients compared to VT(+) patients during follow-up. Some verapamil-ILVT patients who show QRS morphology changes over the follow-up period may become free from VT without any invasive or pharmacological treatments, suggesting that further altered LV fascicular conduction might eliminate the reentry of verapamil-ILVT. © 2017 Wiley Periodicals, Inc.

  5. DIGOXINA E VERAPAMIL INDUZEM HIPERTROFIA EM CARDIOMIÓCITOS DE RATOS SEDENTÁRIOS E/OU TREINADOS

    Directory of Open Access Journals (Sweden)

    Claodete Hasselstrom Neves

    Full Text Available RESUMO Introdução: Cardiotônicos e bloqueadores de canais de cálcio são fármacos que alteram o Ca2+ intracelular e afetam o coração. Objetivo: Avaliar os efeitos da administração de verapamil e digoxina sobre a morfologia cardíaca de ratos submetidos ao treinamento intervalado (TAI. Métodos: Ratos Wistar machos divididos em seis grupos (N = 8: Controle, Digoxina (30,0 µg.kg-1/dia, Verapamil (5,0 mg.kg-1/dia, Treinado, Treinado+digoxina e Treinado+verapamil. O TAI foi realizado em esteira rolante (60 min/dia/60 dias concomitantemente com a administração dos fármacos. Fragmentos do ventrículo esquerdo (VE foram coletados para análise histológica. Resultados: A digoxina e o verapamil aumentaram a área total do VE (p < 0,002, capilares/área VE (p < 0,01 e área de cardiomiócitos (p < 2,8e-10, sendo que, nesta última variável, o verapamil promoveu efeito ainda maior que a digoxina. O TAI aumentou VE/PC (p < 4e-05, o diâmetro interno do VE (p < 2,7e-6, a área de cardiomiócitos (p < 1,8e-6 e reduziu o [Lac] (p < 2,6e-5. Houve interação entre TAI e fármacos na área total (p < 9,8e-5, capilares (p < 0,04, células/área (p < 0,004 e área de cardiomiócitos (p < 2e-16. Conclusão: A digoxina promoveu hipertrofia de cardiomiócitos e, quando associada ao TAI, potencializou a hipertrofia. O verapamil foi mais eficiente em aumentar a área de cardiomiócitos em comparação com a digoxina, porém somente de forma isolada.

  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 cows with induced metritis compared with control cows (P cows with induced metritis, we found an increase in β-glucuronidase activity compared with control cows (P 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. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Directory of Open Access Journals (Sweden)

    Diego C Fernandez

    Full Text Available Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  8. Ischemic conditioning protects from axoglial alterations of the optic pathway induced by experimental diabetes in rats.

    Science.gov (United States)

    Fernandez, Diego C; Pasquini, Laura A; Dorfman, Damián; Aldana Marcos, Hernán J; Rosenstein, Ruth E

    2012-01-01

    Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.

  9. Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

    Science.gov (United States)

    Lavezzo, A; Melillo, G; Clavenna, G; Omini, C

    1992-06-01

    The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough.

  10. 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.

  11. 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.

  12. 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.

  13. Experimental Study of the Laser-Induced Oxyhemoglobin Photodissociation in Cutaneous Blood Vessels

    Directory of Open Access Journals (Sweden)

    Gisbrecht Alexander

    2015-11-01

    Full Text Available A new optical method for reduction of local tissue hypoxia is proposed. It is shown that this method of phototherapy allows the control of a local oxygen concentration in tissue. Different aspects of biomedical application of this phenomenon are discussed. The results of in vivo experimental investigation of the laser-induced photodissociation of oxyhemoglobin in cutaneous blood vessels and its role in tissue oxygenation are presented. The rates of oxygen saturation SpO2 in blood and their dependence on the wavelength of the transcutaneous laser irradiation have been experimentally measured.

  14. Laser induced deflection technique for absolute thin film absorption measurement: optimized concepts and experimental results.

    Science.gov (United States)

    Mühlig, Christian; Kufert, Siegfried; Bublitz, Simon; Speck, Uwe

    2011-03-20

    Using experimental results and numerical simulations, two measuring concepts of the laser induced deflection (LID) technique are introduced and optimized for absolute thin film absorption measurements from deep ultraviolet to IR wavelengths. For transparent optical coatings, a particular probe beam deflection direction allows the absorption measurement with virtually no influence of the substrate absorption, yielding improved accuracy compared to the common techniques of separating bulk and coating absorption. For high-reflection coatings, where substrate absorption contributions are negligible, a different probe beam deflection is chosen to achieve a better signal-to-noise ratio. Various experimental results for the two different measurement concepts are presented.

  15. The effect of verapamil and diltiazem on cardiac stimulant effect of adrenaline and calcium chloride on isolated frog heart

    OpenAIRE

    Lakhavat Sudhakar, Naveen Kumar T, Tadvi NA, Venkata Rao Y

    2013-01-01

    Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus reduce the frequency of opening of these channels in response to depolarization. The result is a marked decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, ...

  16. 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

  17. Clinical and experimental studies on effects of chemotherapeutic agents on radiation-induced pulmonary damage

    Energy Technology Data Exchange (ETDEWEB)

    Wadasaki, Kouichi

    1988-12-01

    Clinical and experimental studies were undertaken to evaluate the effects of chemotherapeutic agents on radiation-induced pulmonary damage. In a clinical study, one hundred patients with lung cancer were retrospectively reviewed in terms of the development of radiation pneumonitis. In the patients treated with radiation and chemotherapy except for cisplatinum, radiation pneumonitis occurred more frequently and severely than patients with radiation alone. In an experimental study, male SD rats received 15 Gy radiation to the right lungs with or without injection of chemotherapeutic agents including cisplatinum, adriamycin or peplomycin. Histological changes and hydroxyproline contents of the lungs were evaluated at 2 or 5 months after treatment. Pulmonary damage was severer in rats with radiation and drugs than those with radiation alone. However, rats with cisplatinum had less damage than those with other drugs. In conclusion, radiation-induced pulmonary damage was enhanced by administration of several chemotherapeutic agents. However, cisplatinum seemed to enhance pulmonary damage less than other drugs. (author) 77 refs.

  18. Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Shahnaz Atabak

    2013-01-01

    Full Text Available Peritoneal dialysis offers several advantages such as better clearance of intermediate/large molecules and better preservation of renal residual function when compared with hemodialysis. However, dialysis adequacy is one of the subjects of concern of this modality. There are some drugs that are capable of influencing solute transport in the peritoneum, such as acetyle co-enzyme inhibitors (ACE-I medications and calcium channel blockers. Captopril and Verapamil are often mentioned, but their use has shown varying conclusions and initial studies were performed with the intra-peritoneal administration of these drugs and there are only a few studies on the effect of the oral administration of these drugs. This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET test. However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti-hypertensive medication of choice in CAPD patients, which can also result in better dialysis adequacy. However, further studies with larger sample sizes are needed in the future.

  19. Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods

    OpenAIRE

    Tan Zi Ning; Wong Weng Kin; Shaymoli Mustafa; Arefuddin Ahmed; Rahmah Noordin; Tan Gim Cheong; Olivos-Garcia Alfonso; Lim Boon Huat

    2012-01-01

    Objective: To compare the efficacy of three different tissue stains, namely haematoxylin and eosin (H&E), periodic-acid Schiff (PAS) and immunohistochemical (IHC) stains for detection of Entamoeba histolytica (E. histolytica) trophozoites in abscessed liver tissues of hamster. Methods: Amoebic liver abscess was experimentally induced in a hamster by injecting 1 × 106 of axenically cultured virulent E. histolytica trophozoites (HM1-IMSS strain) into the portal vein. After a week post-inocul...

  20. 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....

  1. The effect of various drugs on experimentally induced ulcers in immobilized rats

    Science.gov (United States)

    Schramm, H.

    1978-01-01

    Experiments related to the importance of functional disorders in the central nervous system in connection with stomach diseases were performed on Wistar rats. Assuming that severe mental strains may be triggering factors for such disorders, testing of the effects of different drugs on experimentally induced ulcers in these rats was done. The immobilization method described by Bonfils was used. Particular importance was placed on the sex related difference which appeared.

  2. Neuropsychological consequences of experimentally-induced anxiety on working memory performance

    OpenAIRE

    Dunger, Warren

    2016-01-01

    Many theories addressing the complex anxiety-cognition interaction are built upon the notion that working memory is vulnerable to the effects of anxiety. However, most research has utilised studies of trait anxiety which does not allow direct inferences to be made between affect and cognitive performance, or exclude confounds such as pre-existing individual differences. As a result, a systematic review was undertaken to explore the neuropsychological consequences of experimentally-induced sta...

  3. Experimental study of corrosion-induced degradation of reinforced concrete elements

    OpenAIRE

    LOUKIL, Olfa; Adelaide, Lucas; Bouteiller, Véronique; Quiertant, Marc; Chaussadent, Thierry; Ragueneau, Frédéric; Bourbon, Xavier; Trenty, Laurent

    2016-01-01

    Corrosion of steel reinforcement is the main cause of damage for reinforced concrete structures. Iron oxides produced during the corrosion process can induce concrete cracking, loss of adhesion at the steel-concrete interface, loss of reinforcing bar cross-section and even spalling of the concrete cover. In the presented research, the durability problems related to the corrosion of the reinforcement are investigated by combining experimental and numerical studies. However, this paper particul...

  4. 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

  5. The role of experimentally-induced subacromial pain on shoulder strength and throwing accuracy.

    Science.gov (United States)

    Wassinger, Craig A; Sole, Gisela; Osborne, Hamish

    2012-10-01

    Shoulder injuries often comprise two separate yet related components, structural tissue damage and pain. The role of each of these components on shoulder function is difficult to ascertain. Experimental pain models allow the assessment of consequences of localized pain when applied to healthy individuals. By understanding the role of pain on shoulder function, clinicians will be able to more efficiently assess and treat shoulder injuries. The objective of the study was to evaluate the role of experimentally-induced sub-acromial pain on shoulder isokinetic rotational strength and throwing accuracy. This was a block counterbalanced, crossover, repeated measures study design utilizing 20 individuals without self-reported shoulder or cervical pathology. Shoulder function was measured with and without experimental pain injection (2 mL of 5% hypertonic saline) in the sub-acromial space. Functional tasks consisted of shoulder rotational strength utilizing isokinetic testing and throwing accuracy via the functional throwing performance index. The hypertonic saline induced moderate pain levels in all participants (4.3-5.1/10). Normalized shoulder internal (t = 3.76, p = 0.001) and external (t = 3.12, p = 0.006) rotation strength were both diminished in the painful condition compared to the pain free condition. Throwing accuracy was also reduced while the participants experienced pain (t = 3.99, p = 0.001). Moderate levels of experimental shoulder pain were sufficient to negatively influence shoulder strength and throwing accuracy in participants without shoulder pathology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens.

    Science.gov (United States)

    Bábíčková, Janka; Tóthová, Ľubomíra; Lengyelová, Eva; Bartoňová, Anastázie; Hodosy, Július; Gardlík, Roman; Celec, Peter

    2015-10-01

    Sex differences have been found in the incidence and progression of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The reported differences in observational studies are controversial, and the effects of sex hormones on the pathogenesis of IBD are not clear. The aim of this study was to analyze sex differences in the progression of experimentally induced colitis. Experimental colitis was induced in adult mice by adding 2% dextran sodium sulfate (DSS) into drinking water. Male and female mice were used as intact, gonadectomized, and supplemented with either estradiol or testosterone. In comparison to males, female mice with induced colitis had significantly longer colon (p < 0.05), lower decrease in body weight (p < 0.001), and lower stool consistency score (p < 0.05). Histopathological analysis showed less inflammatory infiltrates (p < 0.001) and crypt damage (p < 0.001) in female mice. Female mice with colitis had also lower concentration of TNF-α in colon homogenates (p < 0.01). Supplementation with estradiol in ovariectomized mice ameliorated the severity of colitis. Female mice are partially protected against chemically induced colitis. This protection seems to be mediated by estradiol.

  7. Endocrine profiles of dairy cows following experimentally induced clinical mastitis during early lactation.

    Science.gov (United States)

    Hockett, M E; Hopkins, F M; Lewis, M J; Saxton, A M; Dowlen, H H; Oliver, S P; Schrick, F N

    2000-03-15

    Concentrations of LH, cortisol, estradiol-17beta (E(2)), prolactin and 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM) were determined in cows with experimentally induced clinical mastitis during early lactation. Cows free of intramammary infection (IMI) and in the luteal phase of the estrous cycle were balanced by lactation number and days in milk and assigned to either control (n=5) or treatment (n=5) groups. Treated cows were infected experimentally (day 0), in two mammary quarters, with Streptococcus uberis and developed clinical mastitis within 60 h after inoculation as evidenced by increased mastitis scores, elevated rectal temperatures, mammary swelling and isolation of S. uberis pathogen. Four days following bacterial challenge, blood samples were collected every 20 min for 8 h for determination of PGFM and LH following administration of oxytocin and GnRH, respectively. Blood samples were also collected on days 0, 4 and 7 of the experiment to determine concentrations of E(2), prolactin and cortisol. Four days after bacterial challenge, concentrations of cortisol were higher (P=0.04) in experimentally infected cows than controls. Experimentally challenged cows had increased (P=0.02) concentrations of cortisol on days 4 and 7 compared with day 0. Control cows had no significant increase in blood cortisol during the experimental period. Baseline concentrations of PGFM did not differ between groups; however, peak concentrations of PGFM following oxytocin challenge were elevated (P=0.006) in cows with clinical mastitis compared with control animals. Prolactin, E(2) and LH did not differ between cows with clinical mastitis or controls. Experimentally induced mastitis during early lactation elevated concentrations of cortisol during the luteal phase of the estrous cycle. Furthermore, mastitic cows demonstrated an increased PGFM response following oxytocin administration. Altered reproductive efficiency in cows with clinical mastitis caused by Gram

  8. 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.

  9. Inflammation-induced pain sensitization in men and women: does sex matter in experimental endotoxemia?

    Science.gov (United States)

    Wegner, Alexander; Elsenbruch, Sigrid; Rebernik, Laura; Roderigo, Till; Engelbrecht, Elisa; Jäger, Marcus; Engler, Harald; Schedlowski, Manfred; Benson, Sven

    2015-10-01

    A role of the innate immune system is increasingly recognized as a mechanism contributing to pain sensitization. Experimental administration of the bacterial endotoxin lipopolysaccharide (LPS) constitutes a model to study inflammation-induced pain sensitization, but all existing human evidence comes from male participants. We assessed visceral and musculoskeletal pain sensitivity after low-dose LPS administration in healthy men and women to test the hypothesis that women show greater LPS-induced hyperalgesia compared with men. In this randomized, double-blind, placebo-controlled crossover study, healthy men (n = 20) and healthy women using oral contraceptives (n = 20) received an intravenous injection of 0.4 ng/kg body weight LPS or placebo. Pain sensitivity was assessed with established visceral and musculoskeletal pain models (ie, rectal pain thresholds; pressure pain thresholds for different muscle groups), together with a heartbeat perception (interoceptive accuracy) task. Plasma cytokines (tumor necrosis factor-α and interleukin-6) were measured along with state anxiety at baseline and up to 6-hour postinjection. Lipopolysaccharide application led to significant increases in plasma cytokines and state anxiety and decreased interoceptive awareness in men and women (P < 0.001, condition effects), with more pronounced LPS-induced cytokine increases in women (P < 0.05, interaction effects). Although both rectal and pressure pain thresholds were significantly decreased in the LPS condition (all P < 0.05, condition effect), no sex differences in endotoxin-induced sensitization were observed. In summary, LPS-induced systemic immune activation leads to visceral and musculoskeletal hyperalgesia, irrespective of biological sex. These findings support the broad applicability of experimental endotoxin administration as a translational preclinical model of inflammation-induced pain sensitization in both sexes.

  10. 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.

  11. Being slower, feeling older? Experimentally induced cognitive aging experiences have limited impact on subjective age.

    Science.gov (United States)

    Gabrian, Martina; Wahl, Hans-Werner

    2017-06-01

    Initial experimental research has shown that subjective age may change in response to induced aging experiences, but replication and extension are needed. The present study investigates if age-related cognitive gain or loss experiences evoke decreases/increases in subjective age. A multidimensional subjective age measure was used to explore domain-specific internalization effects. 78 individuals aged 59-70 years were randomly assigned to two experimental conditions and a control group. Participants took a cognitive attention test and received gain-oriented feedback on their accuracy or loss-oriented feedback on their processing speed. A mixed factors analysis of covariance was used to examine changes in feel age, look age, do age, and interest age. After being primed with age-related losses, participants reported older do ages as compared to before the experimental priming. Priming age-related gains had only a marginally significant effect on do age. All other subjective age dimensions remained unaffected by the experimental priming. Although previous research has shown that subjective age can be manipulated experimentally, findings from the present study underscore that a comprehensive and cross-domain improvement of subjective age may require personally relevant and repeated experiences of age-related gains.

  12. 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.

  13. Effects of Guchang Capsule on Dextran Sulphate Sodium-Induced Experimental Ulcerative Colitis in Mice

    Directory of Open Access Journals (Sweden)

    Baoshan Liu

    2016-01-01

    Full Text Available Guchang capsule (GC is a Chinese materia medica standardized product extracted from 15 Chinese traditional medical herbs and it has been clinically used in the treatment of intestinal disease. In this study, in order to extend the research of GC in intestinal disease, we were aiming to evaluate potential effects of GC on dextran sulphate sodium- (DSS- induced murine experimental colitis and to elucidate the underlying mechanisms. GC treatment attenuated DSS-induced body weight loss and reduced the mortality. Moreover, GC treatment prevented DSS-induced colonic pathological damage; meanwhile it inhibited proinflammatory cytokines production in colon tissues. In vitro, GC significantly reduced LPS-induced proinflammatory cytokines production via inhibiting the activation of NF-κB in macrophage cells, and the expressions of several long noncoding RNAs (lncRNAs which were reported in regulating NF-κB signaling pathway were obviously affected by adding GC into culture medium. In conclusion, our data suggested that administration of GC exhibits therapeutic effects on DSS-induced colitis partially through regulating the expression of NF-κB related lncRNAs in infiltrating immune cells.

  14. Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats.

    Science.gov (United States)

    Devaraj, V C; Gopala Krishna, B; Viswanatha, G L; Satya Prasad, V; Vinay Babu, S N

    2011-07-01

    Raphinus sativus Linn (Cruciferae) commonly known as 'Radish' is a multipurpose herb cultivated in different parts of the world for its edible roots and leaves. The present study was aimed to evaluate the antiulcer activity of leaf extracts of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus ligation induced gastric ulcer in rats. The acute oral toxicity study revealed that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth of this dose was selected for evaluation of antiulcer activity. In acetic acid induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered significant protection against acetic acid induced ulcers when compared to control group. While in pylorus ligation induced ulcer model the ERS, EARS and AQRS showed significant protection by decreasing the ulcer index, total acidity and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to possess antiulcer property in the experimental animal models of gastric ulcers, which is consistent with the literature report in the folk medicine.

  15. 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.

  16. 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

  17. Protective activity of gallic acid against glyoxal -induced renal fibrosis in experimental rats

    Directory of Open Access Journals (Sweden)

    Mohammed Jainuddin Yousuf

    2015-01-01

    Full Text Available This study was designed to evaluate the protective activity of gallic acid (GA against glyoxal (GO an advanced glycation intermediate-induced renal fibrosis in experimental rats. Glyoxal (i.p at a dose of 15 mg/Kg body weight/day for 4 weeks induces renal fibrosis. GA was administered orally (100 mg/Kg body weight/day along with GO for 4 weeks. The anti-fibrotic activity of GA was analyzed by measuring the collagen synthesis and deposition in renal tissues using mRNA expression analysis and Masson trichrome staining (MTS, respectively. The nephroprotective potential of GA was assessed by quantifying the markers of kidney damage such as serum blood-urea-nitrogen (BUN, creatinine (CR and alkaline phosphatase (AP. Moreover, basement membrane damage in renal tissues was analysed by periodic acid Schiff’s (PAS staining. GA co-treatment markedly suppressed the GO-induced elevation in mRNA expression of collagen I and III, MMP-2, MMP-9 and NOX (p < 0.05, respectively genes as compared with GO alone infused rats. In addition, GA co-treatment significantly attenuated the GO -induced elevation in serum markers such as BUN, CR and AP levels (p < 0.05, respectively. Furthermore, GA co-treatment restored back the decreased renal super oxide dismutase (SOD activity (p < 0.05 thereby assuage the reactive oxygen species (ROS generation, and maintained the normal architecture of glomerulus. The present study clearly indicates that GO -induces renal fibrosis by enhancing GO/receptor of advanced glycation end product (RAGE induced ROS generation and GA effectively counteracted GO-induced renal fibrosis by its ROS quenching and anti-glycation activity.

  18. Effect of somatosensory amplification and trait anxiety on experimentally induced orthodontic pain.

    Science.gov (United States)

    Cioffi, Iacopo; Michelotti, Ambrosina; Perrotta, Stefania; Chiodini, Paolo; Ohrbach, Richard

    2016-04-01

    The perception of pain varies considerably across individuals and is affected by psychological traits. This study aimed to investigate the combined effects of somatosensory amplification and trait anxiety on orthodontic pain. Five-hundred and five adults completed the State Trait Anxiety Inventory (STAI) and the Somatosensory Amplification Scale (SSAS). Individuals with combined STAI and SSAS scores below the 20th percentile (LASA group: five men and 12 women; mean age ± SD = 22.4 ± 1.3 yr) or above the 80th percentile (HASA group: 13 men and seven women; mean age ± SD = 23.7 ± 1.0 yr) were selected and filled in the Oral Behaviors Checklist (OBC). Orthodontic separators were placed for 5 d in order to induce experimental pain. Visual analog scales (VAS) were administered to collect ratings for occlusal discomfort, pain, and perceived stress. Pressure pain thresholds (PPT) were measured. A mixed regression model was used to evaluate pain and discomfort ratings over the 5-d duration of the study. At baseline, the LASA group had statistically significantly higher PPT values for the masseter muscle than did the HASA group. During the experimental procedure, the HASA group had statistically significantly higher discomfort and pain. A significant difference in pain ratings during the 5 d of the study was found for subjects in the HASA group. Higher OBC values were statistically significantly positively associated with pain. Somatosensory amplification and trait anxiety substantially affect experimentally induced orthodontic pain. © 2016 Eur J Oral Sci.

  19. Experimental study to explore the $\\rm ^8Be$ induced nuclear reaction via the Trojan Horse Method

    CERN Document Server

    Qun-Gang, Wen; Shu-Hua, Zhou; Irgaziev, Bakhadir; Yuan-Yong, Fu; Spitaleri, Claudio; La Cognata, Marco; Jing, Zhou; Qiu-Ying, Meng; Lamia, Livio; Lattuada, Marcello

    2014-01-01

    To explore a possible indirect method for $\\rm ^8Be$ induced astrophysical reactions, the $\\rm ^9Be=({}^8Be+\\it n)$ cluster structure was studied via the Trojan Horse Method. It is the first time to study a super short life nucleus $\\rm ^8Be$ via the Trojan Horse Method, and it is the first time to make a valid test for $l=1$ Trojan-horse nucleus. The $\\rm ^9Be$ nucleus is assumed to have a ($\\rm {}^8Be+\\it n$) cluster structure and used as the Trojan-horse nucleus. The $\\rm ^8Be$ nucleus acts as a participant, while the neutron is a spectator to the virtual $\\rm ^8Be +{\\it d}\\rightarrow \\alpha + {}^6Li$ reaction via a suitable 3-body reaction $\\rm ^9Be +{\\it d}\\rightarrow \\alpha + {}^6Li +\\it n$. The experimental neutron momentum distribution inside $\\rm ^9Be$ was reconstructed. The agreement between experimental and theoretical momentum distribution indicates that there should be a ($\\rm {}^8Be+\\it n$) cluster structure inside $\\rm ^9Be$. Therefor the experimental study of $\\rm ^8Be$ induced reactions, for ...

  20. 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.

  1. Effect of underwater treadmill exercise on postural sway in horses with experimentally induced carpal joint osteoarthritis.

    Science.gov (United States)

    King, Melissa R; Haussler, Kevin K; Kawcak, Christopher E; McIlwraith, C Wayne; Reiser Ii, Raoul F

    2013-07-01

    To evaluate the effect of underwater treadmill exercise on static postural sway in horses with experimentally induced carpal joint osteoarthritis under various stance conditions. 16 horses. On day 0, osteoarthritis was induced arthroscopically in 1 randomly selected middle carpal joint of each horse. Beginning on day 15, horses were assigned to either underwater or overground (without water) treadmill exercise at the same speed, frequency, and duration. Two serial force platforms were used to collect postural sway data from each horse on study days -7, 14, 42, and 70. Horses were made to stand stationary on the force platforms under 3 stance conditions: normal square stance, base-narrow placement of the thoracic limbs, and removal of visual cues (blindfolded) during a normal square stance. The mean of 3 consecutive, 10-second trials in each condition was calculated and used for analysis. Displacement of the center of pressure differed significantly depending on the stance condition. Among horses exercised on the underwater treadmill, postural stability in both the base-narrow and blindfolded stance conditions improved, compared with findings for horses exercised on the overground treadmill. Horses exercised on the overground treadmill were only successful at maintaining a stable center of pressure during the normal square stance position. Variations in stance position had profound effects on the mechanics of standing balance in horses with experimentally induced carpal joint osteoarthritis. Underwater treadmill exercise significantly improved the horses' postural stability, which is fundamental in providing evidence-based support for equine aquatic exercise.

  2. Effects of Ouhyul Herbal Acupuncture on Experimentally Induced Endometrosis in Rats

    Directory of Open Access Journals (Sweden)

    Sang-Suk Yuk

    2006-02-01

    Full Text Available Purpose : Endometriosis is characterized by the ectopic growth of uterine tissue in various extrauterine locations. This study examined the macroscopic, hormonal and immunological effects of Ouhyul Herbal Acupuncture(OHA therapy on rats with experimentally induced endometriosis. Method : Endometrial tissue was implanted in the serosal wall of the small intestine in rats. The rats were divided randomly into an experimental group and control group. The experimental group was treated with OHA on Kwanwon(CV4 three times per week and the control group was administrated normal saline every day. After 6 weeks, the size of the ectopic uterine tissue was estimated and the serum progesterone, estradiol and cytokines(TNF-α, IL-2, IL-4, IL-6, IL-10 concentrations were analyzed. Result : The size of the ectopic uterine tissue in the experimantal group was slightly smaller than that in the control group. The estradiol, IL-4 and IL-6 concentrations were significantly lower and the IL-10 concentration was significantly higher in the serum of the experimental group than in the control group. There was no significant difference in the concentrations of the other cytokines. Conclusion : These results suggest that OHA might be an effective method for treating dometriosis.

  3. Experimentally induced nasal hypersecretion does not reduce the efficacy of intranasal levocabastine

    DEFF Research Database (Denmark)

    Borum, Stefan; Nielsen, K; Bisgaard, H

    1998-01-01

    In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for usage on an as-needed basis, because it has a quick onset of action, and many patients prefer to take medicine only when they have symptoms. It is a prerequisite, however, that nasal hypersecretion during a rhinitis...... episode does not significantly reduce the efficacy of intranasal treatment by washing away the drug before it reaches the H1-histamine receptors. In order to investigate this problem, we have induced nasal hypersecretion with a methacholine challenge in one experiment and in four experiments we have......% (p antihistamine spray. We conclude that experimentally induced nasal hypersecretion does not reduce the efficacy...

  4. Experimental determination of cross section of alpha-induced reactions on natPd

    Science.gov (United States)

    Hermanne, A.; Tárkányi, F.; Takács, S.; Shubin, Yu. N.

    2005-04-01

    Alpha-particle induced nuclear reactions that result in the generation of several Ag (mass numbers 103, 104g, 105, 106m, 110m, 111, 112) and Cd (mass numbers 104, 105, 111m) radionuclides were investigated using the stacked-foil activation technique on natural palladium targets up to Eα = 37 MeV. Excitation functions are reported for the first time for reactions of the type natPd(α, pxn)*Ag (x = 1-5) and natPd(α, xn)*Cd (x = 1-5). The experimental results are compared with model calculations performed with the ALICE-IPPE code. For selected radionuclides useful in medical practice a comparison of possible production routes for α, p and d induced reactions on natPd is discussed.

  5. Experimental determination of activation cross section of alpha-induced nuclear reactions on natPt

    Science.gov (United States)

    Hermanne, A.; Tárkányi, F.; Takács, S.; Shubin, Yu. N.; Kovalev, S.

    2006-10-01

    Alpha-particle induced nuclear reactions that result in the generation of several Hg (mass numbers 192, 193m, 193g, 195m, 195g, 197m, 197g, 199m) and Au (mass numbers 194, 195m, 195g, 196n, 196g, 198m, 198g, 199, 200m) radionuclides were investigated. The stacked-foil activation technique on natural platinum targets was used. Excitation functions are reported for Eα from threshold up to 37 MeV. Cross sections are reported for the first time for reactions of the type natPt(α, xn) ∗Hg ( x = 1-5) and natPd(α,p xn) ∗Au ( x = 1-5). The experimental results are compared with literature values and with model calculations performed with the ALICE-IPPE code. Use of the data for possible applications in comparison with our earlier results for proton and deuteron induced reactions is discussed.

  6. Antistressor activity of Ocimum sanctum (Tulsi) against experimentally induced oxidative stress in rabbits.

    Science.gov (United States)

    Jyoti, S; Satendra, S; Sushma, S; Anjana, T; Shashi, S

    2007-01-01

    Fresh leaves of Ocimum sanctum (O. sanctum) were evaluated for antistress activity against experimentally induced oxidative stress in albino rabbits. Animals of the test group received supplementation of 2 g fresh leaves of O. sanctum per rabbit for 30 days. Anemic hypoxia was induced chemically by injecting the rabbits with 15 mg sodium nitrite per 100 g body weight intraperitoneally. Results indicated that O. sanctum administration blunted the changes in cardiorespiratory (BP, HR, RR) parameters in response to stress. A significant (p sanctum leaves. Significant increase (p sanctum. Oxidative stress led to a lesser depletion of reduced glutathione (28.80%) and plasma superoxide dismutase (23.04%) in O. sanctum-treated rabbits. The results of this study suggest that the potential antistressor activity of O. sanctum is partly attributable to its antioxidant properties.

  7. Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish

    DEFF Research Database (Denmark)

    Haarder, Simon; Kania, Per Walter; Holm, Thomas

    2017-01-01

    with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated...... from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis-inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co-injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48...... hours post-exposure). Gene expression studies of TNBS-treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate-driven immune response was seen in both TNBS...

  8. Experimental and numerical analysis of corrosion induced cover cracking in reinforced concrete beam

    OpenAIRE

    Richard, Benjamin; Quiertant, Marc; Bouteiller, Véronique; Adelaide, Lucas; PERRAIS, Maxime; Tailhan, Jean-Louis; Cremona, Christian

    2010-01-01

    This paper aims to present both experimental and numerical studies of the corrosion induced cracking pattern evolution of a reinforced concrete sample subjected to accelerated corrosion. The sample was a concrete beam (1000x250x100 mm3) reinforced with two rebars (20 mm diameter; 25 mm cover). The beam was not mechanically loaded. The corrosion process was applied on 500 mm rebar length on the central part. Rebars were intentiostatically corroded using a current density of 100µA/cm² of steel,...

  9. Numerical and experimental studies of the carbon etching in EUV-induced plasma

    CERN Document Server

    Astakhov, D I; Lee, C J; Ivanov, V V; Krivtsun, V M; Yakushev, O; Koshelev, K N; Lopaev, D V; Bijkerk, F

    2015-01-01

    We have used a combination of numerical modeling and experiments to study carbon etching in the presence of a hydrogen plasma. We model the evolution of a low density EUV-induced plasma during and after the EUV pulse to obtain the energy resolved ion fluxes from the plasma to the surface. By relating the computed ion fluxes to the experimentally observed etching rate at various pressures and ion energies, we show that at low pressure and energy, carbon etching is due to chemical sputtering, while at high pressure and energy a reactive ion etching process is likely to dominate.

  10. 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.

  11. Direct experimental measurement of SRS-induced spectral tilt in multichannel multispan communication systems

    Energy Technology Data Exchange (ETDEWEB)

    Kapin, Yu A; Nanii, Oleg E; Novikov, A G; Pavlov, V N; Plotskii, A Yu; Treshchikov, V N

    2012-09-30

    Nonlinear SRS-induced tilt of the spectrum of a multichannel DWDM signal is studied experimentally in standard singlemode fibreoptic communication lines. It is found that at a fixed spectral bandwidth and total power the nonlinear SRS tilt is independent of the number of channels, radiation source type, and the initial tilt (positive or negative). In a multispan line consisting of identical spans the total nonlinear tilt of the spectrum (in dB) is proportional to the number of spans, spectral width and total power. (optical fibres, lasers and amplifiers. properties and applications)

  12. The identification of experimentally induced appendicitis using in vitro nuclear magnetic resonance.

    Science.gov (United States)

    Jacobs, D O; Clarke, J R; Settle, R G; Sachdeva, A K; Wheeler, J E; Trerotola, S O; Wolf, G L; Rombeau, J L

    1985-07-01

    Appendicitis was induced in six New Zealand white rabbits. The appendices from these animals had significantly higher spin-lattice relaxation times, T1, as determined in vitro by nuclear magnetic resonance (NMR) (10 controls vs 6 experimentals, 413 +/- 23 vs 455 +/- 41, X +/- SD, P less than (0.02). T1 correlated significantly with the water content of the appendiceal tissue (P less than 0.001). These findings suggest that in vivo NMR imaging techniques weighted on T1 might be able to identify human appendicitis noninvasively by detecting localized edema.

  13. NEURO-SHEILDING EFFECT OF ASIATICOSIDE AGAINST MPTP INDUCED VARIATIONS IN EXPERIMENTAL MICE

    OpenAIRE

    Sampath Uvarajan; Vanisree Arambakkam Janardhanam; Gopal Gopinath

    2012-01-01

    Parkinson’s disease is one of major neurodegenerative disorders caused by endogenous and exogenous neurotoxins. It is characterized by the progressive loss of dopominergic neurons in the substantia nigra pars compacta (SNPc). The present study was aimed to investigate the potential role of asiaticoside against 1 – methyl 4 – phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced neurotoxicity in experimental mice. Mice were divided in to 4 groups : Group I received vehicle saline(0.2ml),group II wa...

  14. Anaesthetic-induced cardioprotection in an experimental model of the Takotsubo syndrome - isoflurane vs. propofol.

    Science.gov (United States)

    Oras, J; Redfors, B; Ali, A; Lundgren, J; Sihlbom, C; Thorsell, A; Seeman-Lodding, H; Omerovic, E; Ricksten, S-E

    2017-03-01

    Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic doses of isoflurane, propofol and ketamine+midazolam on haemodynamics, global and regional LV systolic function and the activation of intracellular metabolic pathways in experimental TS. We hypothesized that cardioprotection in experimental TS is specific for isoflurane. Forty-five rats were randomized to isoflurane (0.6 MAC, n = 15), propofol (bolus 200 mg/kg+360 mg/kg/h, n = 15) or ketamine (100 mg/kg)+midazolam (10 mg/kg, n = 15) anaesthesia. Arterial pressure, heart rate and body temperature were continuously measured and arterial blood gas analysis was performed intermittently. TS was induced by intraperitoneal injection of isoprenaline, 50 mg/kg. LV echocardiography was performed 90 min after isoprenaline injection. Apical cardiac tissue was analysed by global discovery proteomics and pathway analysis. Isoprenaline-induced changes in arterial blood pressure, heart rate or body temperature did not differ between groups. LV ejection fraction was higher and extent of LV akinesia was lower with isoflurane, when compared with the propofol and the ketamine+midazolam groups. In this TS-model, the proteomic analysis revealed an up-regulation of pathways involved in inflammation, coagulation, endocytosis and lipid metabolism. This up-regulation was clearly attenuated with isoflurane compared to propofol. In an experimental model of TS, isoflurane, but not propofol, exerts a cardioprotective effect. The proteomic analysis suggests that inflammation might be involved in pathogenesis of TS. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Sun Woo Lim

    Full Text Available BACKGROUND: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. METHODS: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media. RESULTS: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

  16. 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.

  17. Effect of Induced Mild Hypothermia on Acid-Base Balance During Experimental Acute Sepsis in Rats.

    Science.gov (United States)

    Léon, Karelle; Pichavant-Rafini, Karine; Ollivier, Hélène; L'Her, Erwan

    2015-09-01

    The aim of this study was to determine the effect of induced mild hypothermia (34°C) on acid-base balance in septic rats. Twenty-eight male Sprague-Dawley rats median weight 306 g, range 251-333 g were used. After anesthesia and when the target temperature was reached (normothermia: 38°C or induced mild hypothermia: 34°C), sepsis was induced by cecal ligation and perforation. Measurements of cardiopulmonary parameters and blood samples were performed at T0h (occurring immediately after chirurgical procedures), T2h, T4h (at each temperature), and T6h (at 34°C only). Blood oxygen saturation, heart and respiratory rates, arterial blood pH, carbon dioxide partial pressure, sodium, potassium, chloride and calcium concentrations, hematocrit, blood lactate, tumor necrosis factor-α and interleukin-6 concentrations were measured on anesthetized rats. Other parameters such as bicarbonate concentration, hemoglobin concentration, base excess, and anion gap were estimated from measured parameters. Main results showed that an increase in both cytokines concentrations was observed in septic rats compared with sham rats. This increase was less marked at 34°C compared with 38°C. Moreover, sepsis induction led to a marked metabolic acidosis and hypothermia delayed this acidosis. Induced mild hypothermia delays the evolution of cytokines and metabolic acidosis during experimental sepsis.

  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. Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Song, Xiang Rong; Zheng, Yu; He, Gu; Yang, Li; Luo, You Fu; He, Zhi Yao; Li, Shuang Zhi; Li, Jun Ming; Yu, Shui; Luo, Xun; Hou, Shi Xiang; Wei, Yu Quan

    2010-12-01

    Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92 ± 3.78% and 85.78 ± 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C + Vn or Cn + V) combination and coadministration of two single-agent-loaded PLGANPs (Cn + Vn), which was slightly higher than that of the free VCR/VRP combination (C - V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C + Vn, Cn + V, and Cn + Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  20. Efecto del verapamil sobre la resistencia de Plasmodium falciparum a Cloroquina

    Directory of Open Access Journals (Sweden)

    Moisés Wasserman

    2000-02-01

    Full Text Available

    La resistencia a cloroquina (CQ es una de las principales causas de la recrudescencia de la malaria en el mundo; a pesar de que no se ha elucidado el mecanismo molecular de la cloroquino-resistencia, hay evidencia experimental que sugiere que el fenómeno está asociado con alteraciones en el transporte del medicamento. Aunque aun se debate si la resistencia de P. falciparum a CQ es producto de una rápida salida del medicamento o por el contrario es consecuencia de una menor entrada del fármaco al parásito, se ha reportado que los bloqueadores de canales de calcio como el verapamil (VP, restauran la sensibilidad a CQ en cepas de P. falciparum resistentes al medicamento.

    Los efectos colaterales que producen los medicamentos son una limitación importante cuando se aplica un tratamiento quimioterapéutico; en algunos casos, las dosis tolerables por los pacientes no permiten que los compuestos circulen a concentraciones adecuadas para revertir la resistencia. Una alternativa sería combinar agentes quimioterapéuticos con toxicidades no superpuestas, lo cual permitiría alcanzar un mayor efecto anticloroquino-resistente usando menor cantidad de cada antimalárico. En este estudio analizamos el efecto de la CQ y el VP, cuando son usados de manera aislada o simultánea sobre las cepas 3D7 (sensible a CQ y FCR3 (resistente a CQ de P. falciparum.

    El efecto de CQ y VP fue analizado por medio de una prueba radiométrica. Microplacas de 96 pozos fueron dosificadas con CQ (0, 0.025, 0.05, 0.075, 0.1, 0.15, 0.2, 0.4 y 0.6 m M para 3D7; 0, 0.2, 0.3, 0.4, 0.6, 0.7, 0.8 y 1.0 m

  1. Determination of Verapamil HCl in Pharmaceutical Preparations by a Fluorescent Nano Probe Based on CdTe/CdS/ZnS Quantum Dots

    Directory of Open Access Journals (Sweden)

    Sohail Muhammad

    2017-10-01

    Full Text Available An analytical technique based on fluorescence quenching of CdTe/CdS/ZnS quantum dots (QDs was developed to quantify verapamil in commercially available preparations. Various reaction parameters were optimized and the method developed was validated. One way analysis of variance (ANOVA and post hoc tests at a 5% significance level were performed to justify the significance of the variation in observations. The linear range of the verapamil concentration was 0.25–5 µg/mL while the limit of detection was 20 µg/mL. Recovery and relative standard deviations were not more than ±10% of the actual amount and <5.9%, respectively. Foreign materials, common metal ions and pharmaceutical excipients of dosage forms caused little interference. To verify the application of the analytical method, the quantity of verapamil in commercially available dosage forms was measured. Verapamil content in the tablets and injections was not more than ±10% of the stated amount and it conformed to the specifications of both the British and the United States pharmacopoeias. In the case of statistical analysis, p-value was <0.05 in almost all levels of all parameters except for the optimized level of system. It can be concluded from the results that the designed method is simple, reliable, cost effective, selective, rapid and sensitive enough to be used for quantitative measurement of the verapamil HCl in dosage forms for quality control purposes.

  2. 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.

  3. Polioencefalomalacia experimental induzida por amprólio em ovinos Experimentally amprolium-induced polioencephalomalacia in sheep

    Directory of Open Access Journals (Sweden)

    Fabiano J.F. de Sant'Ana

    2009-09-01

    Full Text Available Para estabelecer um modelo experimental para o estudo da etiologia, patologia e patogênese da polioencefalomalacia em ruminantes, a condição foi induzida em cinco ovinos pela administração oral de amprólio nas doses diárias de 500 e 1.000mg/kg de peso animal, respectivamente por 28-59 dias e 13-39 dias. Todos os ovinos morreram ou foram eutanasiados in extremis após um curso clínico de 3-7 dias. Os sinais clínicos incluíam depressão, incoordenação, midríase, bruxismo, cegueira e decúbito com opistótono e movimentos de pedalagem. Salivação excessiva e posição de cavalete foi observada em um ovino e mioclonias em um outro. Os principais achados de necropsia restringiam-se ao sistema nervoso central e incluíam tumefação do encéfalo com achatamento dos giros telencefálicos e hemorragias nos lobos parietal e occipital do telencéfalo; as hemorragias ocorriam também nas áreas submeníngeas da medula espinhal e do mesencéfalo. Histologicamente, havia necrose segmentar laminar de neurônios (neurônios vermelhos associada a edema, tumefação de células endoteliais, hemorragias e infiltração por macrófagos espumosos (células gitter. Essas alterações eram mais marcadas nos lobos frontal, parietal e occipital do telencéfalo e havia uma demarcação abrupta entre as lesões e o neurópilo normal adjacente. Adicionalmente, lesões semelhantes, mas menos acentuadas, eram observadas no mesencéfalo, tálamo e hipocampo. Levando em consideração a reproducibilidade regular dos aspectos da polioencefalomalacia em ovinos pela administração de amprólio, esse modelo pode ser útil para o estudo da doença.In order to establish an experimental model for the study of the etiology, pathology, and pathogenesis of polioencephalomalacia in ruminants, the condition was induced in five sheep by oral administration of amprolium at daily doses of 500 and 1,000mg per kg of body weight respectively for 28-59 days and for 13-39 days

  4. Polioencefalomalacia experimental induzida por amprólio em bovinos Experimentally amprolium-induced polio-encephalomalacia in cattle

    Directory of Open Access Journals (Sweden)

    Ana Paula A. Nogueira

    2010-08-01

    pathogenesis of polioencephalomalacia (PEM in cattle, the condition was induced into four steers by oral administration of amprolium at daily doses of 500 and 350mg per kg of body weight respectively for 22 and 26-28 days. All steers died spontaneously or were euthanized in extremis after being sick for 4-7 days. Three steers that received the drug at 1,000mg/kg and two that received 500mg/kg died spontaneously with acute or subacute clinical signs and without lesions and signs of PEM. In those steers in which PEM was reproduced, the neurological signs included marked apathy, incoordination, sawhorse stance, occasional falls, hyperexcitability, muscle tremors, blindness, grinding of teeth, strabismus, nystagmus, mydriasis, opisthotonus, and lateral recumbency with paddling movements. Main gross lesions were restricted to the brain and included swelling, flattening, softening and yellow discoloration of the cerebral circumvolutions. Histologically, there was segmental laminar neuronal necrosis (red neurons associated with edema, swelling of endothelial cells, cleavage of laminar neuronal layers or between gray and white matter and moderate to severe infiltration by foamy macrophages (gitter cells. These changes were more marked in the frontal, parietal and occipital telencephalic lobes. Additionally, similar and moderate lesions were detected in the midbrain and hippocampus. Neuronal necrosis and edema affected uniformly the neurons layers of the grey matter of the frontal, parietal and occipital lobes. This experimental model of PEM with oral administration of amprolium may be useful for the study in cattle, as previously observed in sheep.

  5. Experimental and observational evidence for plume-induced subduction on Venus

    Science.gov (United States)

    Davaille, A.; Smrekar, S. E.; Tomlinson, S.

    2017-04-01

    Why Venus lacks plate tectonics remains an unanswered question in terrestrial planet evolution. There is observational evidence for subduction--a requirement for plate tectonics--on Venus, but it is unclear why the features have characteristics of both mantle plumes and subduction zones. One explanation is that mantle plumes trigger subduction. Here we compare laboratory experiments of plume-induced subduction in a colloidal solution of nanoparticles to observations of proposed subduction sites on Venus. The experimental fluids are heated from below to produce upwelling plumes, which in turn produce tensile fractures in the lithosphere-like skin that forms on the upper surface. Plume material upwells through the fractures and spreads above the skin, analogous to volcanic flooding, and leads to bending and eventual subduction of the skin along arcuate segments. The segments are analogous to the semi-circular trenches seen at two proposed sites of plume-triggered subduction at Quetzalpetlatl and Artemis coronae. Other experimental deformation structures and subsurface density variations are also consistent with topography, radar and gravity data for Venus. Scaling analysis suggests that this regime with limited, plume-induced subduction is favoured by a hot lithosphere, such as that found on early Earth or present-day Venus.

  6. Acquired and Congenital Ocular Toxoplasmosis Experimentally Induced in Calomys callosus (Rodentia, Cricetidae

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    Maria de Fátima Pereira

    1999-01-01

    Full Text Available An experimental model for acquired and congenital ocular toxoplasmosis as well as a model to induce experimental autoimmune uveitis (EAU was investigated in Calomys callosus. Toxoplasma gondii, ME-49 strain, was used to infect males and pregnant- and not pregnant-females while S-antigen, a major glycoprotein of the retinal photoreceptor cell, was used to induce EAU. The ocular lesions elicited by T. gondii were characterized by the presence of cysts, free tachyzoites and inflammatory cells in the retina or related tissues. In the congenital form, 40% of the fetus presented ocular lesions, i.e., presence of cysts in the retina, vitreous, and extra-retinal tissues. In the acquired form, 75% of the females and 50% of the males presented unilateral ocular cysts both at 21 and 47 days post-infection. It was also demonstrated that S-antigen was not uveitogenic in the C. callosus model. No lesion was observed in the animals exclusively immunized with this retinal component, even when jacalin was used as additional adjuvant for polyclonal response to the retinal antigen. It can be concluded that C. callosus may constitute in a promising model for study both acquired and congenital ocular toxoplasmosis, particularly when it is important to make sure that a non autoimmune process is involved in the genesis of the ocular infection.

  7. Establishment of peritoneal liquid electrophoretogram from healthy horses and horses submitted to experimentally induced intestinal obstruction

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    A.F.S. Nogueira

    2014-06-01

    Full Text Available The initial inflammatory stages of the colic syndrome include changes known as acute phase response. The aim of this study was to contribute with the establishment of reference values concerning the electrophoretogram of peritoneal liquid from healthy horses and horses submitted to experimentally induced intestinal obstruction. Twenty-one horses were allotted in four groups: duodenal obstruction (DG, ileum obstruction (IG, left-dorsal colon obstruction (MG, and control group (CG. Peritoneal liquid was sampled before obtruction (T0, with 3 hours of obstruction (T3 and 6, 30, 102 and 174 hours after desobstructing (T6, T30, T102 and T174, respectively. Total protein levels were determined by the biuret method and protein fractions were obtained by SDS-PAGE electrophoresis. The acute phase proteins (APP identified were Immunoglobulin-A, ceruloplasmin, transferrin, albumin, α1-antitrypsin, heavy and light chains of immunoglobulin-G, haptoglobin, α1-acid glycoprotein and a still unnamed protein, which was called P24. There was no difference (P>0.3 in protein levels among groups, although a significant difference (P>0.05 was observed between distinct experimental moments in each group evidencing a higher response of the APP in the obstructed groups. The APP fractioning of the peritoneal liquid was standardized to establish a standard curve for healthy equines and those submitted to induced intestinal obstruction. Moreover, it was verified that the SDS-PAGE electrophoresis was sensitive and effective to help diagnose abdominal inflammatory processes.

  8. 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.

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

    CERN Document Server

    Jaiswal, S; Sen, A

    2016-01-01

    We report on experimental observations of flow induced large amplitude dust-acoustic shock waves (DASW) in a complex plasma. The experiments have been carried out in a $\\Pi$ shaped DC 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 of 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 m...

  10. 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.

  11. Assessment of the Mechanistic Role of Cinnarizine in Modulating Experimentally-Induced Bronchial Asthma in Rats.

    Science.gov (United States)

    Abdel-Fattah, Maha M; Messiha, Basim A S; Salama, Abeer A A

    2015-01-01

    Calcium influx, inflammatory infiltration, cytokine production, immunoglobulin E activation and oxidative stress play coordinated roles in bronchial asthma pathogenesis. We aim to assess the protective effect of cinnarizine against experimentally induced bronchial asthma. Bronchial asthma was induced by ovalbumin sensitization and challenge. Rats were allocated into a normal control, an asthma control, a dexamethasone (standard) treatment, and 2 cinnarizine treatment groups. The respiratory functions tidal volume (TV) and peak expiratory flow rate (PEFR), the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-5 (IL-5) in lung tissue, the allergic immunoglobulin IgE in serum, the absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF), as well as the oxidative and nitrosative markers glutathione reduced (GSH) and superoxide dismutase (SOD) in lung tissue and nitric oxide end products (NOx) in BALF were assessed, followed by a histopathological study. Cinnarizine administration significantly restored TV, PEFR, TNF-α, IL-5, IgE, AEC, GSH, SOD and NOx values back to normal levels, and significantly decreased perivascular and peribronchiolar inflammatory scores. Cinnarizine may protect against experimental bronchial asthma. Suppressant effect of cinnarizine on pro-inflammatory cytokines release, IgE antibody production, eosinophil infiltration as well as oxidative and nitrosative stress may explain its anti-asthmatic potential. © 2015 S. Karger AG, Basel.

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

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    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.

  13. Experimental Setup to Assess Blast and Penetration-Induced Secondary Debris in a Military Operations in Urban Terrain (MOUT) Environment

    Science.gov (United States)

    2015-11-01

    in a Military Operations in Urban Terrain (MOUT) Environment by Paul S Duvall Approved for public release; distribution...Research Laboratory Experimental Setup to Assess Blast and Penetration-Induced Secondary Debris in a Military Operations in Urban Terrain...Induced Secondary Debris in a Military Operations in Urban Terrain (MOUT) Environment 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  14. Experimental tonic hand pain modulates the corticospinal plasticity induced by a subsequent hand deafferentation.

    Science.gov (United States)

    Mavromatis, N; Gagné, M; Voisin, J I A V; Reilly, K T; Mercier, C

    2016-08-25

    Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. Sixteen healthy subjects participated in two experimental sessions (Pain, No Pain) in which transcranial magnetic stimulation was used to assess corticospinal excitability in two forearm muscles (flexor carpi radialis and flexor digitorum superficialis) before (T0, T10, T20, and T40) and after (T60 and T75) inflation of a cuff around the wrist. The cuff was inflated at T45 in both sessions and in the Pain session capsaicin cream was applied on the dorsum of the hand at T5. Corticospinal excitability was significantly greater during the Post-inflation phase (p=0.002) and increased similarly in both muscles (p=0.861). Importantly, the excitability increase in the Post-inflation phase was greater for the Pain than the No-Pain condition (p=0.006). Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase (p=0.030) but no difference during the Pre-inflation phase (p=0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle.

    Science.gov (United States)

    Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Riou, Mickaël; Zohari, Siamak; Comtet, Loic; Olofson, Ann-Sophie; Gélineau, Robert; Martin, Guillaume; Elvander, Marianne; Blomqvist, Gunilla; Zientara, Stéphan; Valarcher, Jean Francois

    2014-11-20

    Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV-8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This BTV subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.

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    Johanna Prinz

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.Twenty-two female C57BL/6 (B6 mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE and six months after onset of EAE (long-term EAE. The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT of the spinal cord.B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse

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

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    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.

  18. An automated, high-throughput experimental system for induced charge electrokinetics.

    Science.gov (United States)

    Pascall, Andrew J; Squires, Todd M

    2010-09-21

    Recent experiments in induced charge electrokinetics (ICEK) have shown that the standard theory generally overpredicts experimentally observed velocities. Such discrepancies reduce the efficacy of practical ICEK devices, and highlight our incomplete understanding of electrokinetic phenomena. Here, we present an automated experimental system that allows for the rapid collection of ICEK data under a variety of conditions ( approximately 1000 per day) to help develop and constrain new theories. We demonstrate this system by studying the ICEK slip flows over electrodes that have been controllably "contaminated" with a dielectric layer, either SiO(2) or an alkanethiol self-assembled monolayer, of known thickness. We also develop a theory that accounts for the effects of the dielectric coatings surface chemistry that yields quantitative agreement with experiments over nearly a thousand distinct conditions in the SiO(2) system and present an additional three thousand experiments of flows over alkanethiol monolayers. Our experimental system allows the direct interrogation of the physico-chemical effects that influence ICEK flows and for the optimization of these flows in lab-on-a-chip systems.

  19. Radiological and histopathological evaluation of experimentally-induced periapical lesion in rats

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    Renata Cordeiro Teixeira

    2011-10-01

    Full Text Available OBJECTIVE: This study evaluated experimentally-induced periapical bone loss sites using digital radiographic and histopathologic parameters. MATERIAL AND METHODS: Twenty-seven Wistar rats were submitted to coronal opening of their mandibular right first molars. They were radiographed at 2, 15 and 30 days after the operative procedure by two digital radiographic storage phosphor plates (Digora®. The images were analyzed by creating a region of interest at the periapical region of each tooth (ImageJ and registering the corresponding pixel values. After the sacrifice, the specimens were submitted to microscopic analysis in order to confirm the pulpal and periapical status of the tooth. RESULTS: There was significant statistically difference between the control and test sides in all the experimental periods regarding the pixel values (two-way ANOVA; p<0.05. CONCLUSIONS: The microscopic analysis proved that a periapical disease development occurred during the experimental periods with an evolution from pulpal necrosis to periapical bone resorption.

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

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    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.

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

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    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.

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

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    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.

  3. Microscopic evaluation of induced tooth movement after subluxation trauma: an experimental study in rats

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    Mauro Carlos Agner Busato

    2014-01-01

    Full Text Available OBJECTIVE: The objective of this study was to assess the histological alterations that occurred in the periodontal area of rat molars submitted to induced tooth movement (ITM right after an intentional trauma (subluxation. METHODS: Forty adult male Wistar rats (Rattus norvegicus albinus were selected. The animals were divided into eight groups (n = 5, according to the combination of variables: Group 1 - control (neither trauma nor ITM; Group 2 - ITM; Groups 3, 4, 5 and 6 - dentoalveolar trauma groups corresponding, respectively, to 1, 3, 8 and 10 days after trauma; Groups 7 and 8 - the animals' molars were subjected to a 900 cN impact and, one and three days after the trauma event, tooth movement was induced. The rats' maxillary first molars were mesially moved during seven days with a closed coil (50 cN. After the experimental period of each group, the animals were sacrificed by anesthetic overdose and the right maxillas were removed and processed for histological analysis under light microscopy. RESULTS: In the animals of group 3, 4, 5 and 6, the histological alterations were not very significant. Consequently, the effect of induced tooth movement right after a subluxation event (groups 7 and 8 was very similar to those described for Group 2. CONCLUSION: There was no difference in the quality of periodontal repair when ITM was applied to teeth that had suffered a subluxation trauma.

  4. Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition

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    Wenjie Guo

    2015-10-01

    Full Text Available In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1β release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases.

  5. Effect of DATS on experimental corneal neovascularization induced by corneal suture in rats cornea

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    Xiao-Jun Zhou

    2017-11-01

    Full Text Available AIM: To study the effect of diallyl trisulfide(DATSon experimental corneal neovascularization(CNVin rats induced by corneal suture and detect the expression of vascular endothelial growth factor(VEGFand p-AKT in rats cornea. METHODS: The rat model of corneal neovascularization(CNVwas induced by corneal suture. Rats were randomly divided into Group A: physiological saline control group containing DMSO(10 rats; Group B: 25μmol/L DATS treatment group(10 rats; Group C: 50μmol/L DATS treatment group(10 rats; Group D: 100μmol/L DATS treatment group(10 rats; Group E: 200μmol/L DATS treatment group(10 rats. The occurrence and development of CNV were observed by slit-lamp microscope at 7d after suture, and the area of CNV were calculated.Two weeks later, HE staining was used to observe the pathological organization form of each cornea, and RT-PCR and Western blot were used to detect the expression of VEGF mRNA and protein expression of VEGF and p-AKT between each groups. RESULTS: The blood vessel area of Group C, D and E was compared with that of Group A, the difference was statistically significant(PPPCONCLUSION: DATS can inhibit corneal neovascularization of the rats induced by suture. Its mechanism may be associated with suppression of VEGF secretion, down-regulation of VEGF and inactivation of p-AKT.

  6. Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

    Science.gov (United States)

    Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

    2017-01-01

    Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

  7. Aloe vera gel protects liver from oxidative stress-induced damage in experimental rat model.

    Science.gov (United States)

    Nahar, Taslima; Uddin, Borhan; Hossain, Shahdat; Sikder, Abdul Mannan; Ahmed, Sohel

    2013-05-07

    Aloe vera is a semi-tropical plant of Liliaceae family which has a wide range of applications in traditional medicine. In the present study, we sought to investigate the heptaoprotective potential of Aloe vera gel as a diet supplement. To achieve this goal, we have designed in vitro and in vivo experimental models of chemical-induced liver damage using male Sprague-Dawley rat. In the in vitro model, its effect was evaluated on Fenton's reaction-induced liver lipid peroxidation. Co-incubation with gel significantly reduced the generation of liver lipid peroxide (LPO). Next, to see the similar effect in vivo, gel was orally administered to rats once daily for 21 successive days. Following 1 hour of the last administration of gel, rats were treated with intra-peritoneal injection of CCl4. Dietary gel showed significant hepatoprotection against CCl4-induced damage as evident by restoration of liver LPO, serum transaminases, alkaline phosphatase, and total bilirubin towards near normal. The beneficial effects were pronounced with the doses used (400 and 800 mg/kg body weight). Besides, we did not observe any significant drop in serum albumin, globulin as well as total protein levels of gel-administered rats. Histopathology of the liver tissue further supported the biochemical findings confirming the hepatoprotective potential of dietary gel.

  8. Hematological, antioxidant and protective performance of Usnea longissima on chemical induced hepatotoxicity in experimental animals

    Directory of Open Access Journals (Sweden)

    Pritt Verma

    2017-05-01

    Full Text Available Objective: To investigated the hematological, antioxidant and protective performance of Usnea longissima (U. longissima on CCl4 induced hepatotoxicity in experimental animals. Methods: Hepatotoxicity was induced by CCl4 (1 mL/kg body weigt 1:1 CCl4 i.p., ethanolic U. longissima extracts at a doses (200 and 400 mg/kg body weigt were administered to and compared with Silymarin (25 mg/kg body weigt and hematological, antioxidant and enzymatic, non-enzymatic parameters were assessed through the liver functions test. All the observation was also supplemented with histopathological examination of liver sections. Results: Phytochemical investigation showed that ethanolic extract contains poly phenolic compounds tannins, flavonoids, alkaloids and saponins and acute toxicity study shows that ethanolic extract was safe up to 2 000 mg/kg body weight. The toxicant induced a rise in the plasma enzyme levels of ALT, AST, ALP and total bilirubin level. This increased level was significantly decreased by the extract at 400 mg/kg body weight than 200 mg/kg body weight. The animals were prevented (partly or fully which was showed in the histopathological changes using ethonolic U. longissima extract. Conclusions: The outcome of this study reveals that, there is a powerful antioxidant and hepatoprotective activity of U. longissima. It is believed that the present constituents are responsible for courting the hepatic disease and alternative components have the power to act as free radical scavenging properties.

  9. Extended ceftiofur therapy for treatment of experimentally-induced Streptococcus uberis mastitis in lactating dairy cattle.

    Science.gov (United States)

    Oliver, S P; Almeida, R A; Gillespie, B E; Headrick, S J; Dowlen, H H; Johnson, D L; Lamar, K C; Chester, S T; Moseley, W M

    2004-10-01

    Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, the period around calving, and during early lactation. Strategies for controlling Strep. uberis mastitis are poorly defined and are currently inadequate. Objectives of the present study were to evaluate efficacy of ceftiofur, a new broad-spectrum cephalosporin antibiotic, for treatment of experimentally induced Strep. uberis intramammary infections (IMI) in lactating dairy cows during early lactation and to determine whether extended therapy regimens enhanced efficacy of ceftiofur. Efficacy of extended ceftiofur intramammary therapy regimens was investigated in 37 mammary quarters of 23 dairy cows that developed clinical mastitis following experimental infection with Strep. uberis during early lactation. Cows that developed clinical mastitis during the challenge period were allocated randomly to 3 groups representing 3 different ceftiofur treatment regimens: 2-d (n = 7 mammary quarters), 5-d (n = 16 mammary quarters), and 8-d (n = 14 mammary quarters) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. A bacteriological cure was defined as an experimentally infected quarter that was treated and was bacteriologically negative for the presence of Strep. uberis at 7, 14, 21, and 28 d posttreatment. Percentage of Strep. uberis IMI eliminated was 43, 88, and 100% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Both the 5- and 8-d ceftiofur extended therapy treatment regimens had significantly higher bacterial cure rates than the standard 2-d ceftiofur treatment regimen. The bacterial cure rate of the 8-d ceftiofur extended therapy group was marginally better (P = 0.052) than the 5-d ceftiofur extended therapy group. Results of this study indicate that ceftiofur therapy was effective for eliminating Strep. uberis experimental IMI, and 5- and 8-d extended ceftiofur

  10. «MEMORIES OF FUTURE»: CHANGE IN VERAPAMIL SIGNIFICANCE IN THE TREATMENT OF PATIENTS WITH ISCHEMIC HEART DISEASE AND ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    S. R. Gilyarevskiy

    2015-09-01

    Full Text Available The significance of verapamil in the treatment of patients with ischemic heart disease (IHD and hypertension (HT is considered. Data on the limited role of beta-blockers in the improvement of patient’s status in stable IHD, data about negative effect of heart rate (HR reduction on the central aortic pressure, as well as the relationship between HR and risk of complications in the INVEST trial are presented. Verapamil therapy in patients with HT and IHD without heart failure/systolic dysfunction and/or recent myocardial infarction may have advantages due to achievement of the sufficient antiischemic effect with less HR reduction.

  11. Influência de solventes na disposição cinética e no metabolismo enantiosseletivos do verapamil em ratos

    OpenAIRE

    Fabiano Henrique Mateus

    2007-01-01

    O verapamil (VER) é um composto quiral comercializado como mistura racêmica dos enantiômeros (+)-(R)-VER e (-)-(S)-VER. O VER é biotransformado em norverapamil (NOR) e em outros metabólitos por vias dependentes do CYP. O tolueno e o n-hexano são solventes orgânicos que podem alterar o metabolismo de medicamentos dependente do CYP. Assim, o estudo investiga a estereosseletividade na farmacocinética do verapamil administrado a ratos na dose de 10 mg kg-1, sob forma racêmica, e do seu metabólito...

  12. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice.

    Science.gov (United States)

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry; Moulin, David

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between "colitis" and "arthritis+colitis" groups during colitis development. Interestingly a milder decrease of bacterial diversity in the "arthritis+colitis" group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition.

  13. Experimental colitis delays and reduces the severity of collagen-induced arthritis in mice

    Science.gov (United States)

    Hablot, Julie; Peyrin-Biroulet, Laurent; Kokten, Tunay; El Omar, Reine; Netter, Patrick; Bastien, Claire; Jouzeau, Jean-Yves; Sokol, Harry

    2017-01-01

    Amongst extraintestinal manifestations (EIM) occurring in IBD patients, rheumatologic manifestations are the most frequent. Understanding the relationships between arthritis and colitis is a prerequisite to improving the management of these patients. Microbiota of patients with IBD or rheumatologic diseases, like spondyloarthritis (SpA) is modified compared to healthy individual. Thus, we have evaluated the impact of colitis in the development of arthritis in mice and we have analyzed microbiota changes. Collagen-induced arthritis (CIA) was induced at day 0 in DBA1 mice exposed or not to Dextran Sodium Sulfate (DSS) to induce colitis between day 14 and day 21. Animals were monitored regularly for arthritis and colitis severity (clinical score, hindpaw edema). Fecal microbiota was studied by 16S rRNA deep sequencing at critical time points (D14, D14, D21 & D41). At day 41, histological scoring of the intestines and ankles were performed at the end of experiment. Induction of colitis slightly delayed arthritis onset (2 ± 1 days of delay) and reduced its severity (5.75 ± 1.62 in arthritis only group vs 4.00 ± 1.48 in arthritis + colitis group (p = 0.02 at day 28) macroscopically and histologically. In contrast, colitis severity was not influenced by arthritis development. Induction of colitis promoted a modification of microbiota composition and a decrease of α-diversity. Fecal microbiota composition was different between “colitis” and “arthritis+colitis” groups during colitis development. Interestingly a milder decrease of bacterial diversity in the “arthritis+colitis” group was observed. Concomitant experimental colitis protects mice against collagen-induced arthritis and this is associated with changes in gut microbiome composition. PMID:28926599

  14. Programmed delivery of verapamil hydrochloride from tablet in a capsule device

    Directory of Open Access Journals (Sweden)

    Mukesh Lal Sah

    2012-06-01

    Full Text Available The aim of the present work was to develop a programmed drug delivery system which would be able to release the drug after 6 h of lag time by use of hydrophilic polymers. The capsule body was made impermeable by use of formaldehyde vapor treatment, while the cap was untreated. The capsule was filled with two layered tablets (tablet-in-capsule, followed by a sodium bicarbonate:citric acid mixture (SBCM and lactose as bulking agent. Sodium alginate, chitosan, HPMC K15 and chitosan:sodium alginate complex (CSAC were used as the rate modulating layer. Through combined use of HPMC K15 and adjusting the ratio of CSAC, the desired lag time of 6 h was obtained. The effect of the bulking agents on the lag time were also studied and it was found that the lag time was decreased with higher amounts of lactose, and delayed dissolution and decreased lag time was observed at higher amount of effervescent mixture.O objetivo do presente trabalho foi desenvolver sistema de liberação programada de cloridrato de verapamil capaz de liberação imediata do fármaco após 6 h de intervalo de tempo usando polímeros hidrofílicos. O corpo da cápsula foi impermeabilizado por tratamento de vapor de formaldeído, enquanto a tampa não foi submetida ao tratamento. Dois comprimidos foram inseridos na cápsula (comprimidos em cápsula seguido de mistura de bicarbonato de sódio: ácido cítrico e lactose, utilizados como excipientes. O alginato de sódio, a quitosana, o HPMC K15 e o complexo quitosana:alginato de sódio foram utilizados para modular a razão de liberação do fármaco. A combinação entre o HPMC K15 e o ajuste da proporção do complexo quitosana:alginato de sódio permitiu a liberação do fármaco após 6 h. O efeito dos excipientes na liberação do fármaco foi também avaliado. Verificou-se que o tempo de latência foi reduzido na presença de maior quantidade de lactose, enquanto o menor tempo foi observado empregando maior concentração da

  15. Heart disease induced by AAS abuse, using experimental mice/rats models and the role of exercise-induced cardiotoxicity.

    Science.gov (United States)

    Riezzo, I; De Carlo, D; Neri, M; Nieddu, A; Turillazzi, E; Fineschi, V

    2011-05-01

    The anabolic-androgenic steroids (AAS) are all synthetic derivates of testosterone and are commonly used as sport performance enhancers in athletes. The heart is one of the organs most frequently affected by administration of anabolic steroids. A direct myocardial injury caused by AAS is supposed to determine marked hypertrophy in myocardial cells, extensive regional fibrosis and necrosis. A number of excellent studies, using animal models, were performed to evaluate the cardiac effects of AAS. It is known that exogenous administration induced cardiac hypertrophy in vitro and in vivo, and when combined with exercise, anabolic steroid use has been shown to change exercise-induced physiological cardiac hypertrophy to pathophysiological cardiac hypertrophy. However the molecular mechanisms are still poorly understood. It's described that sudden cardiac death, myocardial infarct; ventricular remodelling and cardiomyopathy do to AAS is related to apoptosis and oxidative stress when associated with exercise. Mechanical stimuli and circulating humoral factors (TNF-α, HSP-70, IL-1β) released by the heart and peripheral organs are responsible. Testosterone and derivates can work through genomic (activation of specific androgen receptor, interaction with coactivators and co-repressors transcription factors, gene regulation) and non-genomic mechanism (membrane-receptor-second messenger cascades). Chronic AAS abuse results in different patterns of pathologic alterations, which depend on type, dose, frequency, and mode of use. The difficulty in interpreting experimental data on animals (mice and rats) lies in the diversity of experiments (the diversity of substances, which show different properties, different mice / rats by sex and age, duration of treatment with AAS, dosages used, type, scope and exercise duration).

  16. Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Echigo Ryosuke

    2012-04-01

    Full Text Available Abstract Background Subarachnoid hemorrhage (SAH frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH. Trehalose is a non-reducing disaccharide in which two glucose units are linked by α,α-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo. Methods Enzyme immunoassay for eicosanoids, pro-inflammatory cytokines, and endothelin-1, and western blotting analysis for cyclooxygenase-2, inducible nitric oxide synthase, and inhibitor of NF-κB were examined in macrophage-like cells treated with hemolysate. After treatment with hemolysate and hydrogen peroxide, the levels of lipid peroxide and amounts of arachidonic acid release were also analyzed. Three hours after the onset of experimental SAH, 18 Japanese White rabbits received an injection of saline, trehalose, or maltose into the cisterna magna. Angiographic and histological analyses of the basilar arteries were performed. In a separate study, the femoral arteries from 60 rats were exposed to fresh autologous blood. At 1, 3, 5, 7, 10, and 20 days after treatment, cryosections prepared from the femoral arteries were histologically analyzed. Results When cells were treated with hemolysate, trehalose inhibited the production of several inflammatory mediators and degradation of the inhibitor of NF-κB and also suppressed the lipid peroxidation, the reactive oxygen species-induced arachidonic acid release in vitro. In the rabbit model, trehalose produced an inhibitory effect on vasospasm after the onset of experimental SAH, while maltose had only

  17. Nanolesions induced by heavy ions in human tissues: Experimental and theoretical studies

    Directory of Open Access Journals (Sweden)

    Marcus Bleicher

    2012-07-01

    Full Text Available The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.

  18. Experimental study of the cross-sections of alpha-particle induced reactions on $^{209}$Bi

    CERN Document Server

    Hermanne, A; Shubin, Yu N; Szucs, Z; Takács, S; Tarkanyi, F; 10.1016/j.apradiso.2005.01.015

    2005-01-01

    alpha -particle-induced nuclear reactions for generation of /sup 211 /At used in therapeutic nuclear medicine and possible contaminants were investigated with the stacked foil activation technique on natural bismuth targets up to E/sub alpha /=39 MeV. Excitation functions are reported for the reactions /sup 209/Bi( alpha ,2n)/sup 211/At, /sup 209/Bi( alpha ,3n)/sup 210/At and /sup 209/Bi( alpha , x)/sup 210/Po. Results obtained from direct alpha -emission measurements and gamma -spectra from decay products are compared and correspond well with earlier literature values. Thick target yields have been deduced from the experimental cross-sections and optimised production pathways for minimal contamination are presented. A comparison with the results of the theoretical model code ALICE-IPPE is discussed.

  19. Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M

    2016-01-01

    Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic......R). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh-cuff deflation caused a MAP reduction of 16 (13-20) % at baseline and 18 (16-20) % after LPS, while the MAP reduction was 12 (11-13) % in patients......(-1) ; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce...

  20. Experimental and numerical study of wave-induced backfilling beneath submarine pipelines

    DEFF Research Database (Denmark)

    Bayraktar, Deniz; Ahmad, Joseph; Eltard-Larsen, Bjarke

    2016-01-01

    ). The time series of scour depths are closely monitored through video recordings. Systematic analysis of these has resulted in aclosed form expression for the backfilling time scale, which is demonstrated to be a full order of magnitude greater than the well-known time scale of scour (with both governed...... primarily by the Shields parameter).The developed expression is strictly valid for the current-to-wave backfilling scenarios considered, while likely serving as an upper limit for more general wave-induced backfilling circumstances. The experiments are complemented by similar backfilling simulations...... utilizing a fully-coupled hydrodynamic and morphodynamic CFD model. The numerical simulations demonstrate the ability of the model to predict backfilling towards expected equilibrium scour depths based on the new wave climate, with time scales reasonably inline with experimental expectations....

  1. The Measurement of Electron-Induced Erosion of Condensed Gases: Experimental Methods

    DEFF Research Database (Denmark)

    Schou, Jørgen; Sørensen, H.; Børgesen, P.

    1984-01-01

    Two experimental methods for measuring the erosion yield of condensed gases are described. One, the frequency-change method, utilizes a quartz-crystal microbalance operating at liquid-helium temperature. The other, the emissivity-change method is based on the strongly varying electron emission...... as a function of the condensed-gas film thickness. Satisfactory results have been obtained for both methods for solid Ne and D2 at electron energies up to 3 keV, and the mutual agreement is good as well. Accurate measurements are affected critically by the beam conditions, particularly if the erosion yield...... depends on the film thickness. The erosion yield has been measured for dominant electron sputtering of solid Ne ( ≈ 28 Ne-atoms/electron) as well as for beam-induced evaporation at 2 keV. In the latter case a clear lateral broadening of the erosion spot is observed....

  2. 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.)

  3. Experimental study and nuclear model calculations of 3He-induced nuclear reactions on zinc

    Science.gov (United States)

    Al-Abyad, M.; Mohamed, Gehan Y.; Ditrói, F.; Takács, S.; Tárkányi, F.

    2017-05-01

    Excitation functions of 3He -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 27MeV, the cross-sections for natZn (3He, xn) 69Ge, natZn(3He, xnp) 66,67,68Ga, and natZn(3He, x)62,65Zn 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.

  4. Induced expression of the antimicrobial peptide melittin inhibits experimental infection by Mycoplasma gallisepticum in chickens.

    Science.gov (United States)

    Lazarev, Vassili N; Stipkovits, Laszlo; Biro, Judit; Miklodi, Dora; Shkarupeta, Marina M; Titova, Galina A; Akopian, Tatiana A; Govorun, Vadim M

    2004-05-01

    The in vivo action of the antimicrobial peptide melittin, expressed from a recombinant plasmid vector, on chickens experimentally infected with Mycoplasma gallisepticum was studied. The plasmid vector pBI/mel2/rtTA includes the melittin gene under the control of an inducible tetracycline-dependent human cytomegalovirus promoter and the gene coding for the trans-activation protein rtTA. Aerosol administration of the vector, followed by infecting the chickens with M. gallisepticum 1226, is shown to inhibit development of infection. The inhibitory action was confirmed by a complex of clinical, pathomorphological, histological and serological studies, and also by comparing the M. gallisepticum reisolation frequency from the respiratory tract and internal organs. The data suggest that plasmid vectors expressing genes of antimicrobial peptides can be considered as potential agents for the prevention and treatment of mycoplasma infections in poultry farming.

  5. Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia.

    Science.gov (United States)

    Cohen, N D; Giguère, S; Burton, A J; Rocha, J N; Berghaus, L J; Brake, C N; Bordin, A I; Coleman, M C

    2016-01-01

    Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. Ten foals with experimentally induced R. equi pneumonia. Pilot treatment trial. Foals with pneumonia induced by intrabronchial instillation of R. equi were randomly allocated to receive either clarithromycin combined with rifampin (CLR + RIF) PO or LG IV, and followed by daily physical examinations and weekly thoracic ultrasonography and serum creatinine concentration determinations until the resolution of clinical signs. Treatment success was defined as the resolution of clinical signs and ultrasonographically identified pulmonary abscesses. All 10 foals were successfully treated. Two of 5 foals treated with LG developed azotemia within 1 week; LG was discontinued and treatment switched to CLR + RIF for these foals. None of the CLR + RIF treated foals developed azotemia. Liposomal gentamicin IV can be effective for treatment of R. equi pneumonia, but nephrotoxicity indicates that an alternative dosing interval or route (such as nebulization) will be needed before LG is adequately safe for clinical use. Larger comparative trials will be needed to evaluate the relative efficacy of a safer LG dosage regimen. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. 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.

  7. 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.

  8. Evaluation of the efficacy of curcumin in experimentally induced acute sinusitis in rats.

    Science.gov (United States)

    Birdane, Leman; Cingi, Cemal; Muluk, Nuray Bayar; San, Turhan; Burukoglu, Dilek

    2016-12-01

    We investigated the possible beneficial effects of curcumin (CMN) in the treatment of sinusitis. An experimentally induced sinusitis model was created in rats, and the results were evaluated histologically. Thirty-two healthy, female Sprague Dawley rats weighing 270 to 310 g each, were randomly divided into four groups. Group 1 was the control group. In Groups 2 to 4, experimentally induced acute sinusitis was developed, and the rats in those groups were given saline, sulbactam-ampicillin, and CMN, respectively, for 10 days. Then all rats were dissected, and samples of sinus mucosa were taken. Histologic examination was performed via light microscopy. In the sinusitis + antibiotic group, values of inflammation, vascular congestion, vascular dilatation, and subepithelial glandular atrophy were significantly higher; and values of mucosal damage and cilia loss, and hyperplasia of goblet cells, were not significantly different from those in the control group. In the sinusitis + CMN group, values of inflammation, vascular congestion, and vascular dilatation were significantly higher; and values of mucosal damage and cilia loss, hyperplasia of goblet cells, and subepithelial glandular atrophy were not significantly different from those of the control group. Histologic examination revealed that in the sinusitis + CMN group, a nearly normal appearance of the epithelial tissue and reduced cellular inflammation in connective tissue were observed. Minimal vascular congestion in connective tissue remained. The efficacy of CMN in acute sinusitis may be related to its potent anti-inflammatory effects on modulation of various inflammatory cytokines. When low side effects are taken into account, CMN therapy may be a promising option in the treatment of acute sinusitis.

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

    Science.gov (United States)

    Oji, Satoru; Nicolussi, Eva-Maria; 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.

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

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    Satoru Oji

    Full Text Available 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.

  11. 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.

  12. Development of an experimental model of neurocysticercosis-induced hydrocephalus. Pilot study.

    Science.gov (United States)

    Hamamoto Filho, Pedro Tadao; Zanini, Marco Antônio; Botta, Fabio Pires; Rodrigues, Marianna Vaz; Bazan, Rodrigo; Vulcano, Luiz Carlos; Biondi, Germano Francisco

    2015-12-01

    To develop an experimental model of neurocysticercosis-induced hydrocephalus There were used 17 rats. Ten animals were inoculated with Taenia crassiceps cysts into the subarachnoid. Five animals were injected with 0. ml of 25% kaolin (a standard solution for the development of experimental hydrocephalus) and two animals were injected with saline. Magnetic resonance imaging (MRI) was used to evaluate enlargement of the ventricles after one or three months of inoculation. Volumetric study was used to quantify the ventricle enlargement. Seven of the 10 animals in the cyst group developed hydrocephalus, two of them within one month and five within three months after inoculation. Three of the five animals in the kaolin group had hydrocephalus and none in the saline group. Ventricle volumes were significantly higher in the 3-months MRI cyst subgroup than in the 1-month cyst subgroup. Differences between cyst subgroups and kaolin group did not reach statistical significance. The developed model may reproduce the human condition of neurocysticercosis-related hydrocephalus, which exhibits a slowly progressive chronic course.

  13. Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

    Science.gov (United States)

    Rath, Heiko C.; Schultz, Michael; Freitag, René; Dieleman, Levinus A.; Li, Fengling; Linde, Hans-Jörg; Schölmerich, Jürgen; Sartor, R. Balfour

    2001-01-01

    Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation. PMID:11254584

  14. Cardioprotective effect of Nerium oleander flower against isoproterenol-induced myocardial oxidative stress in experimental rats.

    Science.gov (United States)

    Gayathri, Veeraraghavan; Ananthi, Subhash; Chandronitha, Chandranayagam; Ramakrishnan, Ganapathy; Lakshmisundaram, Raman; Sundaram, Raman Lakshmi; Vasanthi, Hannah R

    2011-03-01

    Nerium oleander Linn (NOL) an evergreen shrub belonging to the Apocynaceae family has been reported to have a wide spectrum of bioactivities. In in vitro study, the free radical scavenging potential of the hydroethanolic extract of N oleander Linn (ENO) flower and its fractions (glycosidic and nonglycosidic) were studied using 2, 2(')-azino-di [3-ethylbenzthiazoline sulphonate] (ABTS(*+) ) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH*) scavenging assay. ENO exhibited better radical scavenging activities than its fractions. Furthermore, the cardioprotective role of ENO (10, 30, 100 mg/kg, per oral [po]) was tested against isoproterenol-induced myocardial toxicity (ISO, 120 mg/kg per day, subcutaneously [sc], for 2 days at 48 hours interval) in experimental rats when compared to propranolol (5 mg/kg, po) which was the standard. Pretreatment with ENO (10, 30, and 100 mg/kg) and propranolol for 2 weeks followed by ISO challenge in rats prevented the elevation of marker enzymes such as lactate dehydrogenase (LDH), γ-glutamyl transferase (GGT), creatine kinase (CK-MB and creatine phosphokinase [CPK]), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in plasma. In addition, pretreatment with ENO and propranolol significantly attenuated the lipid peroxidation by maintaining the levels of enzymatic (superoxide dismutase and glutathione peroxidase) and nonenzymatic antioxidants (reduced glutathione and nitrite), which was also confirmed histologically. Taken together, the current study indicates that the hydroalcoholic extract of N oleander Linn flowers aid in cardioprotection probably by improving the antioxidant defense system during experimental myocardial necrosis.

  15. Experimental and Numerical Assessment of the Dynamical Behaviour of a Footbridge Under Human-Induced Loads

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    Santos da Silva José Guilherme

    2015-01-01

    Full Text Available This research aims to perform an experimental and numerical assessment of an existing pedestrian footbridge located in the campus of the State University of Rio de Janeiro (UERJ, Rio de Janeiro/RJ, Brazil. The structural system is based on an internal reinforced concrete footbridge spanning 24.5m, constituted by concrete beams and slabs and being currently used for pedestrian crossing. The modal testing of the structure was performed by dynamic monitoring through accelerometers installed on the structure as well as by a vibrometer device based on Laser Doppler Vibrometry using the SIMO and SISO acquisition techniques, respectively. Then, these experimental results were calibrated with a numerical model by the use of finite element method (FEM through the ANSYS program. Afterwards, a forced vibration analysis was performed on the structure based on human-induced loads considering two control groups: the first one is intended to excite the investigated footbridge to cause resonance motion with a controlled step frequency and the second one is related to freely random people crossing the footbridge as it occurs normally during its real life. Thus, the structural system dynamic response in terms of peak accelerations values were evaluated and compared to the current human comfort criteria.

  16. Theoretical analysis and experimental evaluation of laser-induced interstitial thermotherapy in ex vivo porcine pancreas.

    Science.gov (United States)

    Saccomandi, Paola; Schena, Emiliano; Caponero, Michele Arturo; Di Matteo, Francesco Maria; Martino, Margareth; Pandolfi, Monica; Silvestri, Sergio

    2012-10-01

    Laser-induced interstitial thermotherapy (LITT) has been recently applied to pancreas in animal models for ablation purpose. Assessment of thermal effects due to the laser-pancreatic tissue interaction is a critical factor in validating the procedure feasibility and safety. A mathematical model based on bioheat equation and its experimental assessment was developed. The LITT procedure was performed on 40 ex vivo porcine pancreases, with an Nd:YAG (1064 nm) energy of 1000 J and power from 1.5 up to 10 W conveyed by a quartz optical fiber with 300 μm diameter. Six fiber Bragg grating sensors have been utilized to measure temperature distribution as a function of time at fixed distances from the applicator tip within pancreas undergoing LITT. Simulations and experiments show temperature variations Δ T steeply decreasing with distance from the applicator at higher power values: at 6 W, ∆T > 40 °C at 5 mm and Δ T is approximately equal to 5 °C at 10 mm. Δ T nonlinearly increases with power close to the applicator. Ablated and coagulated tissue volumes have also been measured and experimental results agree with theoretical ones. Despite the absence of data in the current literature on pancreas optical parameters, the model allowed a quite good prediction of thermal effects. The prediction of LITT effects on pancreas is necessary to assess laser dosimetry.

  17. 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.

  18. Design and Testing of an Experimental Steam-Induced Burn Model in Rats

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    Vlad Porumb

    2017-01-01

    Full Text Available Background. Most of the current models for experimental burns pose difficulties in ensuring consistency and standardization. Aim of Study. We aimed to develop an automated, reproducible technique for experimental burns using steam-based heat transfer. Methods. The system developed for steam exposure was based on a novel, integrated, computer-controlled design. Three groups of rats were exposed to steam for 1, 3, and 7 seconds. The lesions were evaluated after 20 minutes, 48 hours, and 72 hours after burn induction. Results. One-second steam application produced a superficial second-degree burn; three-second application induced deep second-degree burn; and seven-second application led to a third-degree burn. Conclusion. The high level of automation of our integrated, computer-controlled system makes the difference between our system and other models, by ensuring the control of the duration of exposure, temperature, and pressure and eliminating as many potential human generated errors as possible. The automated system can accurately reproduce specific types of burns, according to histological assessment. This model could generate the reproducible data needed in the study of burn pathology and in order to assess new treatments.

  19. Experimental host preference of diapause and non-diapause induced Culex pipiens pipiens (Diptera: Culicidae).

    Science.gov (United States)

    Faraji, Ary; Gaugler, Randy

    2015-07-24

    Culex pipiens pipiens plays an important role in the transmission of several vector-borne pathogens such as West Nile virus (WNV) in North America. Laboratory and field studies suggest that this species is ornithophilic but because of genetic hybridization with sibling species during the active mosquito season, it may occasionally feed on mammals. Adult female Cx. p. pipiens undergo a facultative diapause and may serve as an overwintering mechanism for WNV. To determine the effect of diapause on the innate host preference of Cx. p. pipiens emerging from winter hibernation, we conducted host-choice experiments using bird and mammal hosts. Mosquitoes were reared under non-diapause induced (NDI), diapause induced (DI), and field collected from overwintering (OW) hibernaculae. They were released into a large mesh enclosure housing two lard can traps, and given a choice between feeding on a dove or a rat. Host seeking Cx. p. pipiens were four times more likely to feed on the dove than the rat, regardless of experimental conditions. Under NDI conditions, Cx. p. pipiens were (p diapause in temperate habitats where winter survival is crucial for disease transmission cycles. Although we showed that Cx. p. pipiens prefers an avian to a mammalian host, nearly 20% of emerging mosquitoes in the spring could feed on mammals. Changes in host preferences may also contain valuable clues about transmission dynamics and subsequent timely interventions by vector control and public health practitioners.

  20. Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

    Science.gov (United States)

    Bolat, D; Oltulu, F; Uysal, A; Kose, T; Gunlusoy, B; Yigitturk, G; Turk, N S; Turan, T

    2016-09-01

    To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p losartan administration, mean JS was significantly increased (p losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. © 2016 Blackwell Verlag GmbH.

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

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    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. Prevention of chemically induced diabetes mellitus in experimental animals by virgin argan oil.

    Science.gov (United States)

    Bellahcen, Said; Mekhfi, Hassane; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Hakkou, Abdelkader; Aziz, Mohammed; Bnouham, Mohamed

    2012-02-01

    The argan tree plays an important socioeconomic and ecologic role in South Morocco. Moreover, there is much evidence for the beneficial effects of virgin argan oil (VAO) on human health. Thus, this study investigated whether administering VAO to rats can prevent the development of diabetes. VAO extracted by a traditional method from the almonds of Argania spinosa (2 mL/kg) was administered orally (for 7 consecutive days) to rats before and during intraperitoneal alloxan administration (75 mg/kg for 5 consecutive days). An alloxan diabetic-induced untreated group and treated by table oil were used as control groups. Body mass, blood glucose and hepatic glycogen were evaluated. In the present study, subchronic treatment with VAO at a dose of 2 mL/kg, before the experimental induction of diabetes, prevented the body mass loss, induced a significant reduction of blood glucose and a significant increase of hepatic glycogen level (p < 0.001) compared with the untreated diabetic group. In conclusion, the present study shows that argan oil should be further investigated in a human study to clarify its possible role in reducing weight loss in diabetics, and even in inhibiting the development or progression of diabetes. This antidiabetic effect could be due to the richness of VAO in tocopherols, phenolic compounds and unsaturated fatty acids. Copyright © 2011 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Martinez, María del Carmen; Ruspini, Silvina Fernanda; Afonso, Susana Graciela; Meiss, Roberto; Buzaleh, Ana Maria

    2015-01-01

    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. PMID:25945334

  4. Antitussive effect of naringin on experimentally induced cough in Guinea pigs.

    Science.gov (United States)

    Gao, Sen; Li, Peibo; Yang, Hongliang; Fang, Siqi; Su, Weiwei

    2011-01-01

    The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Experimental Analysis of the Potential Induced Degradation Effect on Organic Solar Cells

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    S. C. Akcaoğlu

    2017-01-01

    Full Text Available Renewable energy applications are increasing daily, and solar electricity, in the form of photovoltaics, is getting more and more important worldwide. As photovoltaics are connected both in series and in parallel, the panels are exposed to high potentials compared to the ground; thus, high voltage stress (HVS occurs. The scope of this paper is to analyze experimentally the potential induced degradation (PID in organic solar cells. To that end, organic solar cells are manufactured and are then undergone a series of voltage-dependent degradation and time-dependent voltage degradation tests. In addition to that, they are also exposed to gaseous oxygen, oxygen plasma, air degradation, and annealing, and the degradation effects are compared with PID results. From the analysis, it is apparent that annealing, air, gaseous oxygen, and oxygen plasma degradation have similar effects with PID, while due to simple diode characteristics, organic cells proved to be relatively durable to potential induced degradation. At low voltages (10 V, the organic cells withstood degradation adequately, with a drop of 23% in their initial efficiency. As voltage increased, the degradation rate increased considerably reaching a 93% efficiency drop when 30 V was applied for 20 minutes.

  6. 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.

  7. Experimental protoporphyria: effect of bile acids on liver damage induced by griseofulvin.

    Science.gov (United States)

    Martinez, María Del Carmen; Ruspini, Silvina Fernanda; Afonso, Susana Graciela; Meiss, Roberto; Buzaleh, Ana Maria; Batlle, Alcira

    2015-01-01

    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.

  8. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease.

    Science.gov (United States)

    McCarthy, Derrick P; Richards, Maureen H; Miller, Stephen D

    2012-01-01

    Experimental autoimmune encephalomyelitis (EAE) and Theiler's Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD) are two clinically relevant murine models of multiple sclerosis (MS). Like MS, both are characterized by mononuclear cell infiltration into the CNS and demyelination. EAE is induced by either the administration of myelin protein or peptide in adjuvant or by the adoptive transfer of encephalitogenic T cell blasts into naïve recipients. The relative merits of each of these protocols are compared. Depending on the type of question being asked, different mouse strains and peptides are used. Different disease courses are observed with different strains and different peptides in active EAE. These variations are also addressed. Additionally, issues relevant to clinical grading of EAE in mice are discussed. In addition to EAE induction, useful references for other disease indicators such as DTH, in vitro proliferation, and immunohistochemistry are provided. TMEV-IDD is a useful model for understanding the possible viral etiology of MS. This section provides detailed information on the preparation of viral stocks and subsequent intracerebral infection of mice. Additionally, virus plaque assay and clinical disease assessment are discussed. Recently, recombinant TMEV strains have been created for the study of molecular mimicry which incorporate various 30 amino acid myelin epitopes within the leader region of TMEV.

  9. Induced ruminative and mindful attention in everyday life: an experimental ambulatory assessment study.

    Science.gov (United States)

    Huffziger, Silke; Ebner-Priemer, Ulrich; Eisenbach, Christina; Koudela, Susanne; Reinhard, Iris; Zamoscik, Vera; Kirsch, Peter; Kuehner, Christine

    2013-09-01

    Rumination has been proposed as a risk factor for depression, while mindful attention might be protective. Differential effects of these attention foci have so far only been examined in the laboratory. Therefore, we conducted an experimental ambulatory assessment study using ruminative and mindful attention inductions in everyday life to examine their effects in a natural context. Fifty young adults carried palmtops over three weekdays (rumination induction day, mindful attention induction day, noninduction day; randomized cross-over design). Ten times a day, participants rated ruminative self-focus and mood. On the induction days, they were additionally subjected to 3-min inductions of ruminative or mindful attention at each assessment. The two induction modes exhibited differential immediate effects on ruminative self-focus and mood. While induced rumination immediately deteriorated valence and calmness, induced mindful attention specifically enhanced calmness. Depressive symptoms did not moderate these effects. While overall longer term effects of the inductions were missing, the mindful attention day was associated with slightly increasing positive valence over the day. The results need to be replicated in high-risk and patient samples to demonstrate the clinical significance of identified effects. Results confirm the emotional relevance of rumination and mindful attention in real world settings. Future work may test whether adaptive attention-focusing instructions delivered in daily life can support clinical interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice.

    Science.gov (United States)

    Chiabrando, Deborah; Fiorito, Veronica; Marro, Samuele; Silengo, Lorenzo; Altruda, Fiorella; Tolosano, Emanuela

    2013-01-01

    Ferroportin (FPN), the sole characterized iron exporter, is mainly controlled by the peptide hormone hepcidin in response to iron, erythroid factors, hypoxia, and inflammation. In addition, intracellular iron level controls FPN translation by modulating the binding of Iron Responsive Proteins at the 5'UTR of FPN mRNA. Recently, hypoxia inducible factor (HIF)2α has been shown to regulate FPN expression in intestinal cells. Here we show that, during experimentally-induced acute anemia in mice, FPN is regulated at transcriptional level in a cell-specific manner. FPN mRNA level increases in duodenum and spleen macrophages, whereas it does not change in liver and is strongly down-regulated in erythroid precursors. These results were confirmed in Caco2, Raw264.7 and K562 cells treated with a hypoxic stimulus. Moreover, we found a differential expression of HIF1α and HIF2α in cells and tissues that might account for the specificity of FPN regulation. Thus, hypoxia, by directly controlling hepcidin and its target FPN, orchestrates a complex regulatory network aimed at ensuring rapid iron recovery from the periphery and efficient iron utilization in the erythroid compartment. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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    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. 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.

  13. Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish.

    Science.gov (United States)

    Haarder, S; Kania, P W; Holm, T L; von Gersdorff Jørgensen, L; Buchmann, K

    2017-10-01

    Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standards. One of the several factors involved in this question may be reduced exposure to the immunomodulatory effects of parasitic helminths. Several investigations on treatment of mice and humans with helminth-derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune-related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory-secretory (ES) products isolated from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis-inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co-injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48 hours post-exposure). Gene expression studies of TNBS-treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate-driven immune response was seen in both TNBS and TNBS + ES groups, but expression values were significantly depressed for several important pro-inflammatory genes in the TNBS + ES group, indicating protective mechanisms of Anisakis ES compounds on intestinal immunopathology in zebrafish. © 2017 John Wiley & Sons Ltd.

  14. An experimental study on embankment failure induced by prolonged immersion in floodwater

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    Yu-long Luo

    2016-01-01

    Full Text Available Prolonged immersion in floodwater is one of the main causes of embankment failure or dam breaks, although failure mechanisms have not been extensively studied. In this study, an embankment model was constructed to investigate the influence of prolonged immersion in floodwater on the failure of an embankment. The results indicate that: (1 the phreatic surface gradually rises and negative pore pressures gradually dissipate with the time of prolonged immersion in floodwater, and, finally, a stable and fully saturated state is reached; (2 observable cracks and a heave phenomenon are found near the downstream toe and in the top stratum of the foundation, which are attributed to the large uplift pressure on the interface between the top stratum and the pervious substratum, the tremendous impact effect induced by the rapid rise in water level, and the reduction of shear strength of heavy silt loam. The present study enhances our in-depth knowledge of the mechanisms of embankment failure induced by floodwater, and provides experimental data for validation of mathematical models of the embankment seepage failure.

  15. Development of an experimentally induced Streptococcus uberis subclinical mastitis in goats.

    Science.gov (United States)

    Lasagno, Mirta C; Vissio, Claudina; Reinoso, Elina B; Raspanti, Claudia; Yaciuk, Raúl; Larriestra, Alejandro J; Odierno, Liliana M

    2012-01-27

    Streptococcus uberis is a major environmental mastitis-causing pathogen. The infections are predominantly subclinical and are frequently undetected and untreated for extended periods of time. More information about the pathogenesis of S. uberis mastitis would be useful. To our knowledge, no experimental studies into the mastitis pathogenesis caused by S. uberis have been described in lactating goats. The aim of this study was to reproduce an experimentally induced S. uberis subclinical mastitis in lactating goats aimed to evaluate the inflammatory response, dynamics of infection and the pathological findings within the first hours of intramammary inoculation with S. uberis. Six Saanen goats in mid-lactation were inoculated with 1.7 × 10(8)cfu of S. uberis. Bacterial growth peaked in milk from challenged right mammary halves (RMH) at 4h PI. Shedding of viable bacteria showed a marked decrease at 20 h PI. Mean somatic cell counts in milk from the RMH peaked at 20 h PI. Inoculation with S. uberis was followed by a decrease in the mean total number of leukocytes. Signs and systemic symptoms were not evoked by intramammary inoculation. S. uberis could be isolated in tissue from all RMH. Histological examination of specimens of the RMH and lymph nodes of the goats showed an increased inflammatory response throughout the experiment. The histological findings correlated with the immunohistochemical detection of S. uberis in RMH. In conclusion, the experimental inoculation of S. uberis in lactating goats is capable of eliciting an inflammatory response and causing pathological changes, resulting in a subclinical mastitis. This investigation shows that goat might to represent a valuable model for the study of the mastitis pathogenesis caused by S. uberis. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. An experimental study of a circular cylinder's two-degree-of-freedom motion induced by vortex

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    Shin-Woong Kim

    2016-07-01

    Full Text Available This paper presents results of an experimental investigation of vortex-induced vibration (VIV of a flexibly mounted and rigid cylinder with two-degrees-of-freedom with respect to varying ratio of in-line natural frequency to cross-flow natural frequency, f∗, at a fixed low mass ratio. Combined in-line and cross-flow motion was observed in a sub-critical Reynolds number range. Three-dimensional displacement meter and tension meter were used to measure dynamic responses of the model. To validate the results and the experiment system, x and y response amplitudes and ratio of oscillation frequency to cross-flow natural frequency were compared with other experimental results. It has been found that the higher harmonics, such as third and more vibration components, can occur on a certain part of steel catenary riser under a condition of dual resonance mode. In the present work, however, due to the limitation of a size of circulating water channel, the whole test of a whole configuration of the riser at an adequate scale for VIV phenomenon was not able to be conducted. Instead, we have modeled a rigid cylinder and assumed that the cylinder is a part of steel catenary riser where the higher harmonic motions could occur. Through the experiment, we have found that even though the cylinder was assumed to be rigid, the occurrence of the higher harmonic motions was observed in a small reduced velocity (Vr range, where the influence of the in-line response is relatively large. The transition of the vortex shedding mode from one to another was examined by using time history of x and y directional displacement over all experimental cases. We also observed the influence of in-line restoring force power spectral density with f∗.

  17. The IL-33/ST2 pathway controls coxsackievirus B5-induced experimental pancreatitis.

    Science.gov (United States)

    Sesti-Costa, Renata; Silva, Grace K; Proença-Módena, José L; Carlos, Daniela; Silva, Maria L; Alves-Filho, José C; Arruda, Eurico; Liew, Foo Y; Silva, João S

    2013-07-01

    Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8(+) T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2(-/-) mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.

  18. Histopathological characterization of experimentally induced cutaneous loxoscelism in rabbits inoculated with Loxosceles similis venom

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    NB Pereira

    2012-01-01

    Full Text Available Envenomation by Loxosceles bites is characterized by dermonecrotic and/or systemic features that lead to several clinical signs and symptoms called loxoscelism. Dermonecrotic lesions are preceded by thrombosis of the dermal plexus. Recent studies show that atheromatous plaque is prone to thrombosis due to endothelial cell apoptosis. To the best of our knowledge, there are no reports of microscopic dermal lesion and endothelial cell apoptosis induced by Loxosceles similis venom in the literature. Thus, the aim of the present study is to describe histological lesions induced by L. similis venom in rabbit skin and to elucidate whether apoptosis of endothelial cells is involved in the pathogenesis of loxoscelism. Forty male rabbits were split into two groups: the control group (intradermally injected with 50 µL of PBS and the experimental group (intradermally injected with 0.5 µg of L. similis crude venom diluted in 50 µL of PBS. After 2, 4, 6 and 8 hours of injection, skin fragments were collected and processed for paraffin or methacrylate embedding. Sections of 5 µm thick were stained by HE, PAS or submitted to TUNEL reaction. Microscopically, severe edema, diffuse heterophilic inflammatory infiltrate, perivascular heterophilic infiltrate, thrombosis, fibrinoid necrosis of arteriolar wall and cutaneous muscle necrosis were observed. Two hours after venom injection, endothelial cells with apoptosis morphology were evidenced in the dermal plexus. Apoptosis was confirmed by TUNEL reaction. It seems that endothelial cell apoptosis and its consequent desquamation is an important factor that induces thrombosis and culminates in dermonecrosis, which is characteristic of cutaneous loxoscelism.

  19. 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

    2017-08-21

    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.

  20. Experimental study on flow-induced vibration of propeller blades under non-uniform inflow

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    LI Jing

    2017-12-01

    Full Text Available [Objectives] This article presents an experimental study of the flow-induced vibration of propeller blades under periodic inflow, and the dependence of the response on its modes.[Methods] Two seven-bladed highly skewed model propellers of identical proportions but different material are operated in four-cycle and six-cycle inflows to produce a blade vibratory strain response. Two kinds of wire mesh wake screens located 400 mm upstream of the propeller plane are used to generate the four-cycle and six-cycle inflows. A laser Doppler velocimetry system located 100 mm downstream of the wake screen plane is used to measure the axial velocity distributions produced by the wake screens. Strain gauges are attached to the propeller blades at different positions. The data from the strain gauges quantifies the excitation frequencies induced by the wake screens. It is shown that the response will reach peak axial propeller frequency, four times axial propeller frequency and six times axial propeller frequency under uniform inflow, four-cycle inflow and six-cycle inflow respectively.[Results] The effect of resonance on the vibratory strain response is revealed. When six times axial propeller frequency induced by six-cycle inflow coincides with the natural frequency of a flexible propeller, the response of the propeller is at its greatest.[Conclusions] This research reveals that when designing a propeller, it is not sufficient to only focus on its hydrodynamic properties; the effects of the modes of the propeller should also be considered.

  1. The effect of spinal manipulative therapy on experimentally induced pain: a systematic literature review

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    Millan Mario

    2012-08-01

    Full Text Available Abstract Background Although there is evidence that spinal manipulative therapy (SMT can reduce pain, the mechanisms involved are not well established. There is a need to review the scientific literature to establish the evidence-base for the reduction of pain following SMT. Objectives To determine if SMT can reduce experimentally induced pain, and if so, if the effect is i only at the level of the treated spinal segment, ii broader but in the same general region as SMT is performed, or iii systemic. Design A systematic critical literature review. Methods A systematic search was performed for experimental studies on healthy volunteers and people without chronic syndromes, in which the immediate effect of SMT was tested. Articles selected were reviewed blindly by two authors. A summary quality score was calculated to indicate level of manuscript quality. Outcome was considered positive if the pain-reducing effect was statistically significant. Separate evidence tables were constructed with information relevant to each research question. Results were interpreted taking into account their manuscript quality. Results Twenty-two articles were included, describing 43 experiments, primarily on pain produced by pressure (n = 27 or temperature (n = 9. Their quality was generally moderate. A hypoalgesic effect was shown in 19/27 experiments on pressure pain, produced by pressure in 3/9 on pain produced by temperature and in 6/7 tests on pain induced by other measures. Second pain provoked by temperature seems to respond to SMT but not first pain. Most studies revealed a local or regional hypoalgesic effect whereas a systematic effect was unclear. Manipulation of a “restricted motion segment” (“manipulable lesion” seemed not to be essential to analgesia. In relation to outcome, there was no discernible difference between studies with higher vs. lower quality scores. Conclusions These results indicate that SMT has a direct local

  2. The effect of spinal manipulative therapy on experimentally induced pain: a systematic literature review

    Science.gov (United States)

    2012-01-01

    Background Although there is evidence that spinal manipulative therapy (SMT) can reduce pain, the mechanisms involved are not well established. There is a need to review the scientific literature to establish the evidence-base for the reduction of pain following SMT. Objectives To determine if SMT can reduce experimentally induced pain, and if so, if the effect is i) only at the level of the treated spinal segment, ii) broader but in the same general region as SMT is performed, or iii) systemic. Design A systematic critical literature review. Methods A systematic search was performed for experimental studies on healthy volunteers and people without chronic syndromes, in which the immediate effect of SMT was tested. Articles selected were reviewed blindly by two authors. A summary quality score was calculated to indicate level of manuscript quality. Outcome was considered positive if the pain-reducing effect was statistically significant. Separate evidence tables were constructed with information relevant to each research question. Results were interpreted taking into account their manuscript quality. Results Twenty-two articles were included, describing 43 experiments, primarily on pain produced by pressure (n = 27) or temperature (n = 9). Their quality was generally moderate. A hypoalgesic effect was shown in 19/27 experiments on pressure pain, produced by pressure in 3/9 on pain produced by temperature and in 6/7 tests on pain induced by other measures. Second pain provoked by temperature seems to respond to SMT but not first pain. Most studies revealed a local or regional hypoalgesic effect whereas a systematic effect was unclear. Manipulation of a “restricted motion segment” (“manipulable lesion”) seemed not to be essential to analgesia. In relation to outcome, there was no discernible difference between studies with higher vs. lower quality scores. Conclusions These results indicate that SMT has a direct local/regional hypoalgesic effect on

  3. Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier : kinetics and metabolism in the rat

    NARCIS (Netherlands)

    Luurtsema, Gert; Molthoff, Carla F. M.; Schuit, Robert C.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Franssen, Eric J F

    There is evidence that P-glycoprotein (P-gp) in the blood-brain barrier (BBB) may be involved in the aetiology of neurological disorders. For quantification of P-gp function in vivo, (R)-[11C]verapamil can be used as a positron emission tomography (PET) tracer, provided that a mathematical model

  4. VERDICT : The verapamil versus digoxin cardioversion trial: A randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation

    NARCIS (Netherlands)

    Van Noord, T; Van Gelder, IC; Tieleman, RG; Bosker, HA; Tuinenburg, AE; Volkers, C; Veeger, NJGM; Crijns, HJGM

    Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV), The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing)

  5. High-performance liquid chromatographic analysis of verapamil and its application to determination in tablet dosage forms and to drug dissolution studies.

    Science.gov (United States)

    Ozkan, Y; Yilmaz, N; Ozkan, S A; Biryol, I

    2000-05-01

    A high-performance liquid chromatographic procedure with two detectors is presented for the determination of verapamil in pharmaceutical dosage forms. The procedure is based on the use of reversed-phase high-performance liquid chromatography with UV and fluorimetric detectors. Each analysis required no longer than 6 min for both detection procedures. Quantification was achieved by measurement of the ratio of the peak area of the drug to the internal standard (fluoxetine) and the detection limit was 10 ng/ml for the UV detector and 750 pg/ml for the fluorimetric detector. There was no significant difference between inter- and intra-day studies for verapamil determined for two different concentrations (0.05 and 1.00 microgram/ml). This process could be used to determine verapamil concentrations in the range 0.025-50 and 0.0008-20 micrograms/ml for UV and fluorimetric detection, respectively. These methods were applied, without any interference from the excipients, for the determination of the drug in tablets and in drug dissolution studies. It is suggested that the proposed HPLC procedures could be used for routine quality control and dosage form assay of verapamil hydrochloride.

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

    Science.gov (United States)

    Albayrak, Bülent; Cankaya, Erdem; Cetinkaya, Ramazan; Cerrah, Serkan; Bilen, Yusuf

    2016-05-01

    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, trandolapril + 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 comparisons 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 proteinuria 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 proteinuria and MABP. Triple combinations did not have any superiority over double combinations. Therefore, the suitable drug combinations may be chosen according to the clinical status of a patient.

  7. Electroacupuncture-Induced Attenuation of Experimental Epilepsy: A Comparative Evaluation of Acupoints and Stimulation Parameters

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    Xuezhi Kang

    2013-01-01

    Full Text Available The efficacy of electroacupuncture (EA on epilepsy remains to be verified because of previous controversies that might be due to the complexity of the effects induced by different acupoints and stimulation approaches adopted. Therefore, we investigated the effects of EA on epilepsy to determine the specific acupoints and optimal stimulation parameters in this work. Experimental epilepsy was induced by injecting kainic acid to the lateral cerebral ventricle of adult male SD rats. EA with a low-frequency (10 Hz/1 mA or high-frequency (100 Hz/1 mA current was applied to the epileptic model for 30 minutes starting at 0.5 hour after the injection. Four pairs of acupoints were tested, that is, Shuigou (DU26 + Dazhui (DU14, Jinsuo (DU8 + Yaoqi (EXB9, Neiguan (PC6 + Quchi (LI11, and Fenglong (ST40 + Yongquan (KI1. We found that (1 low- or high-frequency EA at different acupoints reduced epileptic seizures (P<0.05 versus the control with an exception of low-frequency EA at Neiguan (PC6 and Quchi (LI11; (2 low-frequency EA induced a better effect at Fenglong (ST40 plus Yongquan (KI1 than that of the other acupoints (P<0.05; (3 there is no significant difference in the effects of high-frequency EA at these acupoints; and (4 the high-frequency EA elicited a greater effect than that of low-frequency EA in all groups (P<0.05, with an exception at Jinsuo (DU8 + Yaoqi (EXB9. The EA-induced attenuation appeared 1–1.5 hours after EA with no appreciable effect in the first hour after EA in either the EEG or the behavioral tests. We conclude that EA attenuation of epileptic seizures is dependent on the stimulation parameters and acupoints and that the delay in appearance of the EA effect could be a reflection of the time required by the EA signal to regulate neural function in the central nervous system.

  8. Relevance of induced and accidental hypothermia after trauma-haemorrhage-what do we know from experimental models in pigs?

    Science.gov (United States)

    Hildebrand, Frank; Radermacher, Peter; Ruchholtz, Steffen; Huber-Lang, Markus; Seekamp, Andreas; Flohé, Sascha; van Griensven, Martijn; Andruszkow, Hagen; Pape, Hans-Christoph

    2014-12-01

    Recent experimental research has either focused on the role of accidental hypothermia as part of the lethal triad after trauma or tried to elucidate the effects of therapeutically induced hypothermia on the posttraumatic course. Induced hypothermia seems to reduce the mortality in experimental models of trauma-haemorrhage. As potential mechanisms, a decrease of cellular metabolism, beneficial effects on haemodynamic function and an attenuation of the inflammatory response have been described. However, negative side effects of hypothermia have to be considered, such as impairment of the coagulatory function and immunosuppressive effects. Furthermore, the optimal strategy for the induction of hypothermia (magnitude, duration, timing, cooling rate, etc.) and subsequent rewarming remains unclear. Nevertheless, this piece of information is essential before considering hypothermia as a treatment strategy for severely injured patients. This review aims to elaborate the differences between accidental and induced hypothermia and to summarize the current knowledge of the potential therapeutic use of induced hypothermia suggested in porcine models of trauma-haemorrhage.

  9. Experimental signature of the pair trajectories of rough spheres in the shear-induced microstructure in noncolloidal suspensions.

    Science.gov (United States)

    Blanc, Frédéric; Peters, François; Lemaire, Elisabeth

    2011-11-11

    The shear-induced microstructure in a semidilute noncolloidal suspension is studied. A high-resolution pair distribution function in the plane of shear is experimentally determined. It is shown to be anisotropic, with a depleted direction close to the velocity axis in the recession quadrant. The influence of roughness on the interaction between particles is quantitatively evidenced. The experimental results compare well with a model from particle pair trajectories.

  10. 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)

  11. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis.

    Science.gov (United States)

    Mohan, Surapaneni Krishna; Veeraraghavan, Vishnu Priya; Jainu, Mallika

    2015-08-01

    Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid.

  12. The effects of Ethanol Extract of Propolis (EEP on the experimentally induced Candida keratitis in rabbits

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    Ahangari AA

    2011-04-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* 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-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Propolis (bee glue is a resinous substance obtained from bee hives living on various plant sources. The purpose of this study was to evaluate the effects of ethanol extract of propolis (EEP on the experimentally induced Candidial keratitis in rabbits."n"nMethods: The alcoholic extract of propolis was prepared by 80% ethyl alcohol. After suppressing the immune system of 24 male rabbits, experimental Candida albicans keratitis was induced in the animals under local anesthesia and sterile conditions. The animals were later divided into four groups including the control or glycerin group and a nystatin and two 500 and 1000µg/ml EEP groups. Treatment continued for 21 days and after sacrificing the animals by humane methods, histopathological samples of the rabbits' eyes were prepared."n"nResults: Keratitis was developed in the eyes of all rabbits a week after the yeast inoculation. In the control group in which animals received glycerin, keratitis persisted until day 21. Clinical signs of keratitis disappeared in the Nystatin and 1000µg/ml EEP groups after 14 and 21 days, respectively. The clinical signs of keratitis partially ameliorated in the animals receiving 500µg/ml EEP. Histopathological examination revealed no differences between groups receiving nystatin or 1000µg/ml EEP."n"nConclusion: It is concluded that, ethanol extract of propolis could completely treat Candida albicans keratitis in 1000µg/ml concentrations. This extract can be used as a safe antifungal agent

  13. 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

  14. Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit.

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    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

  15. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property.

    Science.gov (United States)

    Naik, Suresh R; Thakare, Vishnu N; Patil, Snehal R

    2011-07-01

    The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats. Copyright © 2010 Elsevier GmbH. All rights reserved.

  16. Cartilage integrity and proteoglycan turnover are comparable in canine experimentally induced and human joint degeneration

    Directory of Open Access Journals (Sweden)

    Femke Intema

    2010-10-01

    Full Text Available The value of experimental models of osteoarthritis (OA largely depends on the ability to translate observations to human OA. Surprisingly, direct comparison of characteristics of human and experimental OA is scarce. In the present study, cartilage integrity and matrix turnover in a canine model of joint degeneration were compared to human clinical OA. In 23 Beagle dogs, joint degeneration was induced in one knee, the contra-lateral knee served as a control. For comparison, human osteoarthritic and healthy knee cartilage were obtained at arthroplasty (n=14 and post-mortem (n=13. Cartilage was analyzed by histology and biochemistry. Values for cartilage integrity and proteoglycan (PG synthesis showed species specific differences; GAG content of healthy cartilage was 2-fold higher in canine cartilage and PG synthesis even 8-fold. However, the relative decrease in PG content between healthy and OA cartilage was similar for humans and canines (-17% vs. -15%, respectively, as was the histological damage (+7.0 vs. +6.1, respectively and the increase of PG synthesis (+100% vs. +70%, respectively. Remarkably, the percentage release of total and of newly formed PGs in human and canine controls was similar, as was the increase due to degeneration (+65% vs. +81% and +91% vs. +52%, respectively. Despite differences in control conditions, the observed changes in characteristics of cartilage integrity and matrix turnover are similar in a canine model of joint degeneration and human clinical OA. The canine Groove model shows that its characteristics reflect those of human OA which makes the model appropriate for studying human OA.

  17. Experimental study of laser-induced plasma: Influence of laser fluence and pulse duration

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xueshi; Ma, Qianli; Perrier, Maxime; Motto-Ros, Vincent [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne cedex (France); Sabourdy, David; Nguyen, Luc; Jalocha, Alain [CILAS Laser Company, Photonics Department, 45000 Orléans (France); Yu, Jin, E-mail: jin.yu@univ-lyon1.fr [Institut Lumière Matière, UMR5306 Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne cedex (France)

    2013-09-01

    Influence of laser fluence and pulse duration on the morphology and the internal structure of plasma induced by infrared nanosecond laser pulse on an aluminum target placed in an argon ambient gas of one atmosphere pressure was experimentally studied. Dual-wavelength differential spectroscopic imaging was used in the experiment, which allowed observing the detailed structure inside of the ablation plume with distributions of species evaporated from the target as well as contributed by the ambient gas. Different regimes of post-ablation interaction were investigated using different laser fluences and pulse durations. We demonstrate in particular that plasma shielding due to various species localized in different zones inside of the plume leads to different morphologies and internal structures of the plasma. At moderate fluence, the plasma shielding due to the ablation vapor localized in the central part of the plume leads to its nearly spherical expansion with a layered structure of the distribution of different species. At higher fluence, the plasma shielding becomes strongly contributed by ionized ambient gas localized in the propagation front of the plume. An elongated morphology of the plume is observed with a zone of mixing between different species evaporated from the target or contributed by the ambient gas. Finally with extremely strong plasma shielding by ionized ambient gas in the case of a long duration pulse at high fluence, a delayed evaporation from the target is observed due to the ejection of melted material by splashing. - Highlights: • Morphology and internal structure of a plasma were experimentally determined. • Laser fluence and pulse duration are critical parameters for plasma structure. • Plasma shielding due to various species leads to different plasma structures. • Different regimes of laser-support absorption wave are used for interpretation. • Splashing ejection is observed for strong plasma shielding with long pulse.

  18. 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.

  19. Microdissection studies of the structural alterations induced in rat kidneys by experimental postischemic acute renal failure.

    Science.gov (United States)

    Fetterman, G H; Studnicki, F M; Hashida, Y

    1987-01-01

    A unique opportunity presented itself for a morphologic study of experimental unilateral acute renal failure (ARF) in male rats. The ARF had been induced in the rats by temporary occlusion (1h) of the left renal artery. Twenty-nine rats were divided into subsets as follows: 2-3 h, 24 h, 1 week, 2, 4, 8, and 12 weeks following release of occlusion. Microdissection showed a heterogeneous population of abnormally structured proximal tubules in which the regressive lesions of tubular necrosis were combined with the progressive reaction of repair. The lesions demonstrated are reminiscent of those which have been described in ARF in the human and in experimental animals. Many proximal tubules in the 2- to 3-hour subset presented 1-3 disruptive lesions (DLs) while greater numbers of proximal tubules from the 24-hour group presented 1-5 DLs. Many proximal tubules presented no DLs, but nearly all from the 24-hour subset (97-100%) displayed a squamate appearance which paralleled and was caused by acute tubular necrosis. At 1 week, a dilated pars recta was common, but by this time, the squamate pattern had disappeared. Many casts were present. At 2 weeks, many fewer casts were present in proximal tubules and none were seen at 4, 8 or 12 weeks. The nephrons, particularly the proximal tubules, presented a variety of structural alterations at 2, 4, 8 and 12 weeks. Changes of special interest include (1) the presence of swan-necks; (2) a distinctive squamate appearance of the proximal tubules in the animals killed at 24 h; (3) a spiral, curled appearance caused by differential hyperplasia in animals at 4, 8 and 12 weeks, and (4) a tendency for ischemic lesions to involve all layers of the renal cortex.

  20. Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups.

    Science.gov (United States)

    Bailey, Zachary S; Hubbard, W Brad; VandeVord, Pamela J

    2016-01-01

    Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma.

  1. Experimentally induced pyogenic arthritis of rabbit knees: comparative study of MR imaging and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sung Hwan; Koh, Sung Hye; Chung, Hye Won; Lee, Kyung Won; Kim, Chong Jai; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2002-12-01

    To compare the MR imaging findings of experimentally induced pyogenic arthritis of rabbit knees with the corresponding histopathologic findings. Infection was induced in 20 rabbit knees by direct intra-articular injection of staphylococcus aureus. The animals were divided into four groups of five rabbits each, and spin-echo sagittal T1- and T2-weighted images were obtained 3 days, 1 week, 2 weeks, and 4 weeks, respectively, after staphylococcal inoculation. MR-pathologic correlation was performed, with emphasis on intra-and extra-articular soft tissue lesion characteristics. Soft tissue lesion signal intensity (SI) was classified as low, iso, or high on the basis of that of muscle, and high SI was further subdivided into three categories. At T2-weighted imaging, all soft tissue lesion showed high SI. Pathologic examination revealed the presence of inflammatory cell infiltration (n=2), abscess (n=1), granulation tissue (n=3), fibrosis (n=11), edema (n=4), congestion (n=9), and joint fluid (n=11). Except for the abscess, these lesions were irregular in shape and had variable SI (grade 1-3) and at T2WI could not, therefore, be differentiated. In nine knees, extra-articular soft-tissue lesions were demonstrated at T2WI and correlated with infectious soft tissue lesions such as inflammatory cell infiltration, abscess, granulation tissues and fibrosis; and non-infectious reactive soft tissue changes such as edema and congestion. In pyogenic arthritis, the MR imaging features of soft tissue lesions varied and were nonspecific, depending on the histopathologic abnormalities observed. Our results indicate that in assessing the extent of pyogenic arthritis with MR imaging, caution is required.

  2. 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.

  3. Effects of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Liu, De-shan; Gao, Wei; Liang, Er-shun; Wang, Shu-li; Lin, Wei-wei; Zhang, Wei-dong; Jia, Qing; Guo, Rui-chen; Zhang, Ji-dong

    2013-08-15

    This study was designed to investigate the effect and mechanism of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction in rats. Fifty male Wistar rats were randomly divided into five groups: the normal control rats (NC), the high-methionine-diet rats (Met), the high-methionine-diet rats treated with folic acid, vitaminB₆ and vitaminB₁₂ (Met+F), or with low-dose allicin (Met+L), or with high-dose allicin (Met+H). After 6 weeks, we collected blood samples of all groups to determine plasma endothelin (ET), serum homocysteine (Hcy), nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and detected the expression of basic fibroblast growth factors (bFGF), transforming growth factor beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in the aorta. The Hcy and the expression of TGF-β in both the Met+L and Met+H groups were significantly lower than the Met and Met+F groups. The ET, ET/NO ratio and the MDA levels of the Met+L and Met+H groups were significantly lower than the Met group. The SOD and NO levels and the expression of bFGF, TNF-α and ICAM-1 of the Met+L and Met+H groups were significantly higher than the Met group. Our data indicate that allicin inhibits lipid peroxidation induced by hyperhomocysteinemia and regulates the excretion and equilibrium of ET and NO, and suggest that allicin might be useful in the prevention of endothelial dysfunction caused by hyperhomocysteinemia. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2015-03-01

    Full Text Available This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone’s phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives—5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin—were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes.

  5. Beneficial effect of Citrus limon peel aqueous methanol extract on experimentally induced urolithic rats.

    Science.gov (United States)

    Sridharan, Badrinathan; Michael, Shiju T; Arya, Ramachandran; Mohana Roopan, Selvaraj; Ganesh, Rajesh N; Viswanathan, Pragasam

    2016-01-01

    Citrus limon (L.) Burm.f. (Rutaceace) is a commonly available fruit variety with high medicinal and industrial values. Lemon peel (LP) extract was studied as a potent preventive and curative agent for experimentally induced hyperoxaluric rats. Gas chromatography-mass spectrometry (GC-MS) analyses and toxicity study were performed for aqueous methanol LP extract. Twenty-four Wistar rats were segregated into four groups. Group 1: Control; Group 2: Urolithic (ethylene glycol (EG) - 0.75%); Group 3: Preventive study (EG + LP extract administration from 0th to 7th week); Group 4: Curative study (EG + LP extract administration from 4th to 7th week). Animals received LP extract daily by oral administration (100 mg/kg body weight) for 7 weeks. GC-MS analyses revealed that compound 6 was abundant in the LP extract (32%) followed by compound 1 (∼21%). The LD50 value of LP extract was found to be >5000 mg/kg of body weight. Urolithic rats showed significantly higher urinary calcium and oxalate (4.47 ± 0.44 and 18.86 ± 0.55 mg/24 h, respectively) excretion compared with control and experimental rats. Renal function parameters like urea (84 ± 8.5 and 96.1 ± 3.6 mg/dL), creatinine (1.92 ± 0.27 and 1.52 ± 0.22 mg/dL), and urinary protein (2.03 ± 0.02 and 2.13 ± 0.16 mg/24 h) were also reduced by LP extract (p < 0.001) and corroborated with tissue analyses (SOD, catalase, and MDA levels) and histological studies in normal and experimental animals. Immunohistochemical staining of THP and NF-κB in urolithic animals showed elevated expression than the control, while LP extract suppressed the expression of these proteins. In conclusion, lemon peel is effective in curing kidney stone disease and also can be used to prevent the disease and its recurrence.

  6. 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

    traditional antiarrhythmic drugs have no effect or even worsen the arrhythmias, especially during episodes with elevated sympathetic activity. Verapamil significantly reduces plasma norepinephrine levels and the norepinephrine release during ischemia, whereby ventricular arrhythmias may be prevented. Also...... 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...

  7. Experimental and statistical investigation of thermally induced failure in reactor fuel particles

    Energy Technology Data Exchange (ETDEWEB)

    Lunsford, J.L.; Imprescia, R.J.; Bowman, A.L.; Radosevich, C.E.

    1980-10-01

    An incomplete experimental study into the failure statistics of fuel particle for the high-temperature gas-cooled reactor (HTGR) is described. Fuel particles failure was induced by thermal ramping from room temperature to temperatures in the vicinity of 2273/sup 0/K to 2773/sup 0/K in 2 to 30 h and detected by the appearance of /sup 85/Kr in the helium carrier gas used to sweep the furnace. The concentration of krypton, a beta emitter, was detected by measuring the current that resulted when the helium sweep gas was passed through an ionization chamber. TRISO fuel particles gave a krypton concentration profile as a function of time that built up in several minutes and decayed in a fraction of an hour. This profile, which was temperature independent, was similar to the impulse response of the ionization chamber, suggesting that the TRISO particles failed instantaneously and completely. BISO fuel particles gave a krypton concentration profile as a function of time that built up in a fraction of an hour and decayed in a fraction of a day. This profile was strongly temperature dependent, suggesting that krypton release was diffusion controlled, i.e., that the krypton was diffusing through a sound coat, or that the BISO coating failed but that the krypton was unable to escape the kernel without diffusion, or that a combination of pre- and postfailure diffusion accompanied partial or complete failure.

  8. Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods.

    Science.gov (United States)

    Ning, Tan Zi; Kin, Wong Weng; Mustafa, Shaymoli; Ahmed, Arefuddin; Noordin, Rahmah; Cheong, Tan Gim; Alfonso, Olivos-Garcia; Huat, Lim Boon

    2012-01-01

    To compare the efficacy of three different tissue stains, namely haematoxylin and eosin (H&E), periodic-acid Schiff (PAS) and immunohistochemical (IHC) stains for detection of Entamoeba histolytica (E. histolytica) trophozoites in abscessed liver tissues of hamster. Amoebic liver abscess was experimentally induced in a hamster by injecting 1 × 10(6) of axenically cultured virulent E. histolytica trophozoites (HM1-IMSS strain) into the portal vein. After a week post-inoculation, the hamster was sacrificed and the liver tissue sections were stained with H&E, PAS and IHC stains to detect the amoebic trophozoite. The three stains revealed tissue necrosis and amoebic trophozoites, but with varying clarity. H&E and PAS stained the trophozoites pink and magenta, respectively, however it was difficult to differentiate the stained trophozoites from the macrophages because of their similarity in size and morphology. On the other hand, IHC stain revealed distinct brown appearance of the trophozoites in the infected liver tissues. It can be concluded that out of the three stains, IHC is the best for identification of E. histolytica trophozoites in tissue sections.

  9. A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Indraneel Saha

    2015-01-01

    Full Text Available Objectives. Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats. Methods. Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed. Results. Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitated β-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1 and glucose transporter 2 (GLUT-2, were found to be activated by arecoline at the protein level. Conclusion. It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

  10. Automated segmentation and quantification of actin stress fibres undergoing experimentally induced changes.

    Science.gov (United States)

    Rogge, H; Artelt, N; Endlich, N; Endlich, K

    2017-11-01

    The actin cytoskeleton is a main component of cells and it is crucially involved in many physiological processes, e.g. cell motility. Changes in the actin organization can be effected by diseases or vice versa. Due to the nonuniform pattern, it is difficult to quantify reasonable features of the actin cytoskeleton for a significantly high cell number. Here, we present an approach capable to fully segment and analyse the actin cytoskeleton of 2D fluorescence microscopic images with a special focus on stress fibres. The extracted feature data include length, width, orientation and intensity distributions of all traced stress fibres. Our approach combines morphological image processing techniques and a trace algorithm in an iterative manner, classifying the segmentation result with respect to the width of the stress fibres and in nonfibre-like actin. This approach enables us to capture experimentally induced processes like the condensation or the collapse of the actin cytoskeleton. We successfully applied the algorithm to F-actin images of cells that were treated with the actin polymerization inhibitor latrunculin A. Furthermore, we verified the robustness of our algorithm by a sensitivity analysis of the parameters, and we benchmarked our algorithm against established methods. In summary, we present a new approach to segment actin stress fibres over time to monitor condensation or collapse processes. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

  11. Experimentally induced aggressiveness in adult children of alcoholics (ACOAs): preliminary behavioral and neuroendocrine findings.

    Science.gov (United States)

    Gerra, G; Zaimovic, A; Sartori, R; Raggi, M A; Bocchi, C; Zambelli, U; Timpano, M; Zanichelli, V; Delsignore, R; Brambilla, F

    1999-11-01

    This study was conducted to determine the nature of the reaction of nonalcoholic adult children of alcoholic (ACOA) fathers to the experimental induction of aggression. Of particular interest was the relationship between biochemical factors and personality traits during a stressful event experienced by persons at risk for alcoholism. Aggression was induced by a modified free-operant procedure in 14 ACOA and 14 non-ACOA subjects between 18 and 19 years of age with men and women represented in equal numbers. Neurotransmitter-hormonal assays from blood drawn immediately before, and 20 and 30 minutes after, starting the test included norepinephrine (NE), epinephrine (EPI), prolactin (PRL), growth hormone (GH) and cortisol (Cort). Personality traits were assessed by the Minnesota Multiphasic Personality Inventory (MMPI) Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). During the aggression induction session, ACOAs gained (F = 4.6, 1/13 df, p aggressiveness among ACOAs. Higher baseline plasma levels of Cort (F = 9.8, 1/13 df, p aggression in ACOAs in association with monoaminergic and endocrine changes.

  12. Methyglyoxal administration induces modification of hemoglobin in experimental rats: An in vivo study.

    Science.gov (United States)

    Banerjee, Sauradipta

    2017-02-01

    Methylglyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the present study, the effect of methylglyoxal on experimental rat hemoglobin in vivo has been investigated with respect to structural alterations and amino acid modifications, after external administration of the α-dicarbonyl compound in animals. Different techniques, mostly biophysical, were used to characterize and compare methylglyoxal-treated rat hemoglobin with that of control, untreated rat hemoglobin. In comparison with methylglyoxal-untreated, control rat hemoglobin, hemoglobin of methylglyoxal-treated rats (32mg/kgbodywt.dose) exhibited slightly decreased absorbance around 280nm, reduced intrinsic fluorescence and lower surface hydrophobicity. The secondary structures of hemoglobin of control and methylglyoxal-treated rats were more or less identical with the latter exhibiting slightly increased α-helicity compared to the former. Compared to control rat hemoglobin, methylglyoxal-treated rat hemoglobin showed higher stability. Peptide mass fingerprinting analysis revealed modifications of Arg-31α, Arg-92α and Arg-104β of methylglyoxal-treated rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to be associated with the observed structural alterations of the heme protein. Considering the increased level of methylglyoxal in diabetes mellitus as well as its high reactivity, AGE-induced modifications may have physiological significance. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats

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    Henry Kaminski

    2016-11-01

    Full Text Available The differential susceptibility of skeletal muscle by myasthenia gravis (MG is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM, diaphragm (DIA, and extensor digitorum (EDL of rats with experimental autoimmune MG (EAMG to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated by qPCR. Across the three muscles between the experiment and control groups, three hundred and fifty-nine probes (1.16% with greater than 2 fold changes in expression in 7 of 9 series pairwise comparisons from 31,090 probes were identified with approximately two-thirds being increased. The three muscles shared 16 genes with increased expression and 6 reduced expression. Functional annotation demonstrated that these common expression changes fell predominantly into categories of metabolism, stress response, and signaling. Evaluation of specific gene function indicated that EAMG led to a change to oxidative metabolism. Genes related to muscle regeneration and suppression of immune response were activated. Evidence of a differential immune response among muscles was not evident. Each muscle had a distinct RNA profile but with commonality in gene categories expressed that are focused on muscle repair, moderation of inflammation, and oxidative metabolism.

  14. A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

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    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.

  15. Experimental Leishmania major infection suppresses HIV-1 DNA vaccine induced cellular immune response.

    Science.gov (United States)

    Robinson, Tara M; Nelson, Robin; Artis, David; Scott, Phillip; Boyer, Jean D

    2004-01-01

    The AIDS epidemic in the developing world represents a major global crisis and an effective vaccine is imperative. However, many parasites are common in developing countries and can result in a state of chronic immune activation that is polarized towards a Th2 profile and which can potentially impair responses to vaccines or other infectious challenges. In this study we demonstrate that experimental Leishmania major infection of BALB/c mice inhibits responses to a DNA-based HIV-1 gag vaccine. L. major infection in BALB/c results in a polarized Th2 immune response. In this study naïve BALB/c mice immunized with the HIV-1 gag DNA vaccine mounted a cellular immune response against the vaccine antigen, HIV-1 gag. CD8+ T lymphocytes were able to respond in vitro to HIV-1 gag stimulation and secrete interferon (IFN)-gamma. However, L. major-infected, vaccinated BALB/c mice had a significantly reduced number of IFN-gamma-producing CD8+ T cells following in vitro stimulation with gag antigen. These data suggest that parasitic infection, which results in a Th2 profile, reduces the efficacy of DNA vaccines that are designed to induce antiviral CD8+ T cell responses. Copyright 2004 S. Karger AG, Basel

  16. Acid-base balance in sheep with experimentally induced acute ruminal lactic acidosis

    Directory of Open Access Journals (Sweden)

    A.F. Sabes

    Full Text Available ABSTRACT This study aimed to investigate the changes in the acid-base balance of sheep with experimentally induced acute ruminal lactic acidosis (ARA. Ten ewes orally received 15 grams of sucrose per kilogram of body mass. Arterial blood samples for blood gas analysis were obtained at the following intervals: before the induction of ARA (control, and 2, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 hours after sucrose administration. Urine samples for pH measurement were obtained at the following times: -15 days, -7 days, and immediately before sucrose administration, then at 24, 48, 72, 96, 120 and 144 hours. Thereafter, both blood and urine samples were obtained on the 2nd, 3rd, and 4th following weeks. From 4 hours after the induction, elevation of the pH, bicarbonate and base excess on the arterial blood was observed. After 12 hours, the animals showed a decrease of these parameters, as well as urine acidification, which are symptomatic of metabolic acidosis. Within 28 hours, all parameters were normalized except the base excess, which only returned to normal after 72 hours. Despite the occurrence of acidemia, there was no need for medication and no animals died.

  17. Comparison of Experimental Diabetic Periodontitis Induced by Porphyromonas gingivalis in Mice

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    Qi Wang

    2016-01-01

    Full Text Available Periodontitis is one of the severe complications in diabetic patients and gingival epithelium plays an initial role on the onset and progression of this disease. However the potential mechanism is yet sufficiently understood. Meanwhile, the research on the correlational experimental animal models was also insufficient. Here, we established periodontitis with type 2 diabetes in db/db and Tallyho/JngJ (TH mice and periodontitis with type 1 diabetes in streptozotocin induced diabetes C57BL/6J (STZ-C57 mice by oral infection of periodontal pathogen Porphyromonas gingivalis W50. We demonstrated that periodontal infected mice with high blood glucose levels showed dramatically more alveolar bone loss than their counterparts, in which infected db/db mice exhibited the most bone defects. No contrary impact could be observed between this periodontal infection and onset and severity of diabetes. The expressions of PTPN2 were inhibited whereas the expression of JAK1, STAT1, and STAT3 increased dramatically in gingival epithelia and the serum TNF-α also significantly increased in the mice with diabetic periodontitis. Our results indicated that the variations of inflammation-related protein expressions in gingival epithelia might lead to the phenotype differences in the mice with diabetic periodontitis.

  18. Numerical and experimental study of the thermal stress of silicon induced by a millisecond laser

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xi; Qin Yuan; Wang Bin; Zhang Liang; Shen Zhonghua; Lu Jian; Ni Xiaowu

    2011-07-20

    A spatial axisymmetric finite element model of single-crystal silicon irradiated by a 1064 nm millisecond laser is used to investigate the thermal stress damage induced by a millisecond laser. The transient temperature field and the thermal stress field for 2 ms laser irradiation with a laser fluence of 254 J/cm{sup 2} are obtained. The numerical simulation results indicate that the hoop stresses along the r axis on the front surface are compressive stress within the laser spot and convert to tensile stress outside the laser spot, while the radial stresses along the r axis on the front surface and on the z axis are compressive stress. The temperature of the irradiated center is the highest temperature obtained, yet the stress is not always highest during laser irradiation. At the end of the laser irradiation, the maximal hoop stress is located at r=0.5 mm and the maximal radial stress is located at r=0.76 mm. The temperature measurement experiments are performed by IR pyrometer. The numerical result of the temperature field is consistent with the experimental result. The damage morphologies of silicon under the action of a 254 J/cm{sup 2} laser are inspected by optical microscope. The cracks are observed initiating at r=0.5 mm and extending along the radial direction.

  19. Collision induced dissociation study of azobenzene and its derivatives: computational and experimental results

    Science.gov (United States)

    Rezaee, Mohammadreza; Compton, Robert

    2015-03-01

    Experimental and computational investigation have been performed in order to study the bond dissociation energy of azobenzene and its derivatives using collision induced dissociation method as well as other energy and structural characteristics. The results have been verified by comparing with results obtained from computational quantum chemistry. We used different density functional methods as well as the Möller-Plesset perturbation theory and the coupled cluster methods to explore geometric, electronic and the spectral properties of the sample molecules. Geometries were calculated and optimized using the 6-311 + + G(2d,2p) basis set and the B3LYP level of theory and these optimized structures have been subjected to the frequency calculations to obtain thermochemical properties by means of different density functional, Möller-Plesset, and coupled cluster theories to obtain a high accuracy estimation of the bond dissociation energy value. The results from experiments and the results obtained from computational thermochemistry are in close agreement. Physics and Astronomy Department

  20. Mitigation of DMBA-induced mammary carcinoma in experimental rats by antiangiogenic property of Kalpaamruthaa.

    Science.gov (United States)

    Sathish, Sivaprakasam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2011-06-01

    Extra cellular matrix (ECM) and basement membrane (BM) are important layers that regulate cell structure, cell migration, and cellular proliferation. Degradation of both ECM and BM mediated by proteases favors the tumor invasion and promotes angiogenesis. Female Sprague-Dawley rats weighing 180 ± 10 g were categorized into 6 groups. Group-1 animals served as vehicle control. Group-2 to Group-4 animals were administered with 7,12-dimethylbenz(a)anthracene (25 mg/rat dissolved in olive oil, orally) on day 1 of experimental period to induce mammary carcinoma. (After 90 days, mammary carcinoma was confirmed by histopathological examination). Group-3 and Group-4 rats were subsequently treated with Semecarpus anacardium nut milk extract (SA) and Kalpaamruthaa (KA), respectively. Group-5 and Group-6 animals served as drug control for SA and KA, respectively. Pro-angiogenic factors like proteases, cyclooxygenase-2, and vascular endothelial growth factor were elevated in tumor-bearing animals and decreased in SA- and KA-supplemented rats. Increased levels of these angiogenic factors in tumor-bearing rats indicate the progression of mammary tumor. The decreased levels of these angiogenic in SA- and KA-treated rats may be due to the ameliorative effect of phenolic compounds such as flavonoids, tannins, and other compounds present in the drug.

  1. 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.

  2. Experimental Comparison of Photothermal Conversion Efficiency of Gold Nanotriangle and Nanorod in Laser Induced Thermal Therapy.

    Science.gov (United States)

    2017-11-26

    An experimental comparison of the photothermal conversion efficiency (PCE) for gold nanotriangles (GNTs) and nanorods (GNRs) was carried out in the present work. The discrete dipole approximation method was applied to identify the spectral characteristic of GNTs and GNRs with different aspect ratios. On this basis, the PCE of GNTs and GNRs in photothermal therapy were compared theoretically. Afterwards, an in vitro experiment was adopted to investigate the thermal effect of porcine muscle induced by laser irradiation, with and without injected GNTs and GNRs. The influences of laser total power, nanoparticle concentration, and nanoparticle type were investigated. It was found that for the commonly-used wavelengths for photothermal therapy, the PCE of GNTs is higher than that of the GNRs. Furthermore, for GNRs loaded in tissue in vitro, high laser power and high concentration of nanoparticles leads to the degeneration and even carbonization of tissue. However, for the GNTs with the same situation (laser power, nanoparticle volume concentration, and heating time), it could lead to the tissue's evaporation instead of carbonization.

  3. Experimental studies of the deuteron-induced activation cross-sections on natAg.

    Science.gov (United States)

    Uddin, M S; Baba, M; Hagiwara, M; Tarkanyi, F; Ditroi, F; Takacs, S; Hermanne, A

    2006-09-01

    Excitation functions were measured for the (nat)Ag(d,x)(105,106m,110m)Ag, (nat)Ag(d,x)(107,109)Cd and (27)Al(d,x)(24)Na reactions by the stacked-foil activation technique and high-resolution gamma-spectroscopy over the energy range 0.44-40 MeV. The thick target integral yields were deduced using the measured cross-sections. No experimental data on the (nat)Ag+d process are available in the literature above 27 MeV. The nuclides (105)Ag, (106m)Ag and (109)Cd produced with deuteron induced activation of natural silver have suitable yields and decay characteristics important for thin layer activation (TLA) analysis. The cross-section for the production of (107)Cd and (109)Cd is significantly large. Therefore, the Ag+d process can be an efficient route for the production of isotope with a medium energy accelerator. The results of the model calculation using the TALYS code are not consistent with the present data. A large shift in the incident energy is found in TALYS calculations.

  4. Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Itay Raphael

    2017-07-01

    Full Text Available There is an urgent need in multiple sclerosis (MS patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood–brain barrier (BBB is tightly regulated, whereas, in MS, central nervous system (CNS inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here, we sought to determine if changes in serum NDICPs are detectable prior to clinical onset of experimental autoimmune encephalomyelitis (EAE and, therefore, enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE that pre-onset expression waves of synapsin-2, glutamine synthetase, enolase-2, and synaptotagmin-1 enable the prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggesting hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.

  5. Induced Cannibalism in Experimental Populations of the Forensic Indicator Chrysomya putoria Wiedemann (Diptera: Calliphoridae).

    Science.gov (United States)

    Botteon, V W; Fernandes, F S; Godoy, W A C

    2016-04-01

    We analyzed the behavior of third-instars of Chrysomya putoria as potential cannibals in experimental populations. Cannibalism rates were evaluated in three settings observed for 3, 6, 9, and 24 h, placing injured and uninjured larvae of C. putoria together. Our data heavily support that C. putoria larvae behave as cannibals when induced by a wound in another larva, and also after starving for 24 h. The probability of cannibalism increased as a function of time, both in no-choice and in choice experiments evidencing that time is a determining factor for cannibalism induction in C. putoria. However, the treatment combining injured with uninjured larvae showed the highest probability of cannibalism. These results suggest that C. putoria larvae may cannibalize under scarcity of food over long time or the presence of injured larvae. This study is useful to understand the behavior of C. putoria feeding on ephemeral substrates such as carrion or corpses and brings relevant and significant contribution to population ecology of blowflies and also forensic entomology.

  6. Immunologic responses against hydrolyzed soy protein in dogs with experimentally induced soy hypersensitivity.

    Science.gov (United States)

    Puigdemont, Anna; Brazís, Pilar; Serra, Montserrat; Fondati, Alessandra

    2006-03-01

    To assess whether dogs with experimentally induced type I hypersensitivity against soy protein would respond to soy hydrolysate and develop cutaneous or gastrointestinal tract reactions after intradermal and oral challenge exposure. 12 naïve Beagle pups (9 sensitized and 3 control dogs). 9 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization period, serum concentrations of soy-specific IgE were determined and an intradermal test was performed to confirm the dogs were sensitized against soy protein. An intradermal challenge test and an oral challenge test with native and hydrolyzed soy protein were conducted on 6 sensitized and 2 control dogs. High serum concentrations of soy-specific IgE and positive results for the intradermal test were observed for the 9 sensitized dogs after completion of the sesitization process. Sensitized dogs challenge exposed with hydrolyzed soy protein had a reduced inflammatory response after intradermal injection and no clinical response after an oral challenge exposure, compared with responses after intradermal and oral challenge exposure with native soy protein. Soy-sensitized dogs did not respond to oral administration of hydrolyzed soy protein. Thus, hydrolyzed soy protein may be useful in diets formulated for the management of dogs with adverse reactions to food.

  7. Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies

    Directory of Open Access Journals (Sweden)

    Marco Cascella

    2017-06-01

    Full Text Available Background: Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that Nigella sativa (NS, or its isolated compound Thymoquinone (TQ, has a potential role in combating chemotherapy-induced nephrotoxicity. AIM: To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications. Design: Standard systematic review and narrative synthesis. Data Sources: MEDLINE, EMBASE databases were searched for relevant articles published up to March 2017. Additionally, a manual search was performed. Criteria for a study’s inclusion were: conducted in animals, systematic reviews and meta-analysis, containing data on nephroprotective effects of NS/TQ compared to a placebo or other substance. All strains and genders were included. Results: The database search yielded 71 studies, of which 12 (cisplatin-induced nephrotoxicity 8; methotrexate-induced nephrotoxicity 1; doxorubicin-induced nephrotoxicity 2; ifosfamide-induced nephrotoxicity 1 were included in this review. Conclusions: Experimental animal studies showed the protective effect of NS, or TQ, on chemotherapy-induced nephrotoxicity. These effects are caused by decreasing lipid peroxidation and increasing activity of antioxidant enzymes in renal tissue of chemotherapy-treated animals.

  8. Effects of experimentally induced pain and fear of pain on trunk coordination and back muscle activity during walking.

    NARCIS (Netherlands)

    Lamoth, C.J.C.; Daffertshofer, A.; Meijer, O.G.; Moseley, G.; Wuisman, P.I.J.M.; Beek, P.J.

    2004-01-01

    OBJECTIVE: To examine the effects of experimentally induced pain and fear of pain on trunk coordination and erector spinae EMG activity during gait. DESIGN: In 12 healthy subjects, hypertonic saline (acute pain) and isotonic saline (fear of pain) were injected into erector spinae muscle, and

  9. 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 ...

  10. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Surapaneni Krishna Mohan

    2015-08-01

    Results:The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showedsignificant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid.

  11. Efficacy of Methylene Blue in an Experimental Model of Calcium Channel Blocker Induced Shock

    Science.gov (United States)

    Jang, David H.; Donovan, Sean; Nelson, Lewis S.; Bania, Theodore C.; Hoffman, Robert S.; Chu, Jason

    2014-01-01

    BACKGROUND Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. While supportive care is the mainstay of treatment, experimental therapies such as high dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. Methylene blue acts as both a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cGMP. Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study was to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. METHODS Sprague-Dawley rats were anesthetized, ventilated and instrumented for continuous blood pressure and heart rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg/hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline (NS) with 15 rats in each group. Rats received methylene blue at 2 mg/kg over 5 mins or an equivalent amount of NS in three intervals from the start of the protocol: Minute 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed using Fisher’s exact test and Kaplan Meier survival analysis with the log rank test. RESULTS Overall, 1/15 (7%) rats in the saline-treated group survived to 120 minutes compared with 5/15 (33%) rats in the methylene blue-treated group (difference −26%, 95% CI –54%, 0.3%). The median survival time for the NS group was 42 min (95% CI, 28.1,55.9) and the methylene blue group was 109 min (95% CI, 93.9,124.1). Heart rate and MAP differences between groups were analyzed until 60 minutes

  12. CT and MRI of experimentally induced mesenteric ischemia in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Klein, H.M.; Seggewib, C.; Weghaus, P.; Kamp, M.; Guenther, R.W. [Univ. of Technology, Aachen (Germany)] [and others

    1996-03-01

    Our goal was to assess the value of CT and MRI for the detection of bowel wall changes in experimentally induced mesenteric ischemia. In 18 female pigs. a percutaneous embolization of the superior mesenteric artery was performed with buthyl-2-cyanoacrylate and Lipoidal (1:1) (experimental group). In six animals, only diagnostic imaging and histologic evaluation were performed (control group). CT was carried out 3, 6, and 12 h after occlusion. Incremental CT (1 s scan time, 5 mm slice thickness, 7 mm increment, 120 kV/290 mAs) and spiral CT (slice thickness 5 mm, pitch 1.5, 120 kV/165 mA) were performed pre and post contrast injection (Somatom Plus/ Siemens). Serial CT was carried out after intravenous contrast injection (I ml/kg, 2 ml/s). MRI (Magnetom 1.5 T: Siemens) was performed with T1 (pre and post 0.01 mmol/kg Gd-DTPA; Magnevist; Schering. Germany), T2, and proton density images in axial orientation. Slice thickness was 3 mm and slice gap 1 mm. Additionally, a T1-weighted GE sequence was obtained in dynamic technique (before and 30, 60, and 90 s after contrast agent injection) with a slice thickness of 5 mm. Biometrical monitoring included blood pressure, heart frequency, blood cell count, electrolyte status, blood gas analysis, and determination of serum lactate. Image evaluation included morphological analysis and determination of the enhancement pattern. Histological specimens were obtained and analyzed according to the Chiu classification. The histologic workup of the specimen 3, 6, and 12 h after vascular occlusion revealed an average Chiu state 3, 4, and 5. On CT, the bowel wall had a thickness of 4.7 mm on average in the ischemic segments. There was a significant difference from the control group. Free intraperitoneal fluid and intramural gas were seen after 12 h of ischemia in 80%. In ischemic bowel segments, no mural enhancement was seen. Normal segments and the bowel of the control animals showed an enhancement of 34 HU on average.

  13. CT and MRI of experimentally induced mesenteric ischemia in a porcine model.

    Science.gov (United States)

    Klein, H M; Klosterhalfen, B; Kinzel, S; Jansen, A; Seggewiss, C; Weghaus, P; Kamp, M; Töns, C; Günther, R W

    1996-01-01

    Our goal was to assess the value of CT and MRI for the detection of bowel wall changes in experimentally induced mesenteric ischemia. in 18 female pigs, a percutaneous embolization of the superior mesenteric artery was performed with buthyl-2-cyanoacrylate and Lipiodol (1:1) (experimental group). In six animals, only diagnostic imaging and histologic evaluation were performed (control group). CT was carried out 3, 6, and 12 h after occlusion. Incremental CT (1 s scan time, 5 mm slice thickness, 7 mm increment, 120 kV/290 mAs) and spiral CT (slice thickness 5 mm, pitch 1.5, 120 kV/165 mA) were performed pre and post contrast injection (Somatom Plus/Siemens). Serial CT was carried out after intravenous contrast injection (1 ml/kg, 2 ml/s). MRI (Magnetom 1.5 T; Siemens) was performed with T1 (pre and post 0.01 mmol/kg Gd-DTPA; Magnevist; Schering, Germany), T2, and proton density images in axial orientation. Slice thickness was 3 mm and slice gap 1 mm. Additionally, a T1-weighted GE sequence (multislice FLASH 2D) was obtained in dynamic technique (before and 30, 60, and 90 s after contrast agent injection) with a slice thickness of 5 mm. Biometrical monitoring included blood pressure, heart frequency, blood cell count, electrolyte status, blood gas analysis, and determination of serum lactate. Image evaluation included morphological analysis and determination of the enhancement pattern. Histological specimens were obtained and analyzed according to the Chiu classification. The histologic workup of the specimen 3, 6, and 12 h after vascular occlusion revealed an average Chiu state 3, 4, and 5. On CT, the bowel wall had a thickness of 4.7 mm on average in the ischemic segments. There was a significant difference from the control group (average 3 mm). Free intraperitoneal fluid and intramural gas were seen after 12 h of ischemia in 80%. In ischemic bowel segments, no mural enhancement was seen. Normal segments and the bowel of the control animals showed an enhancement of

  14. Entamoeba histolytica calreticulin: an endoplasmic reticulum protein expressed by trophozoites into experimentally induced amoebic liver abscesses.

    Science.gov (United States)

    González, Enrique; de Leon, Maria del Carmen García; Meza, Isaura; Ocadiz-Delgado, Rodolfo; Gariglio, Patricio; Silva-Olivares, Angelica; Galindo-Gómez, Silvia; Shibayama, Mineko; Morán, Patricia; Valadez, Alicia; Limón, Angelica; Rojas, Liliana; Hernández, Eric G; Cerritos, René; Ximenez, Cecilia

    2011-02-01

    Entamoeba histolytica calreticulin (EhCRT) is remarkably immunogenic in humans (90-100% of invasive amoebiasis patients). Nevertheless, the study of calreticulin in this protozoan is still in its early stages. The exact location, biological functions, and its role in pathogenesis are yet to be fully understood. The aim of the present work is to determine the location of EhCRT in virulent trophozoites in vivo and the expression of the Ehcrt gene during the development of experimentally induced amoebic liver abscesses (ALA) in hamsters. Antibodies against recombinant EhCRT were used for the immunolocalization of EhCRT in trophozoites through confocal microscopy; immunohistochemical assays were also performed on tissue sections of ALAs at different times after intrahepatic inoculation. The expression of the Ehcrt gene during the development of ALA was estimated through both in situ RT-PCR and real-time RT-PCR. Confocal assays of virulent trophozoites showed a distribution of EhCRT in the cytoplasmic vesicles of different sizes. Apparently, EhCRT is not exported into the hepatic tissue. Real-time RT-PCR demonstrated an over-expression of the Ehcrt gene at 30 min after trophozoite inoculation, reaching a peak at 1-2 h; thereafter, the expression fell sharply to its original levels. These results demonstrate for the first time in an in vivo model of ALA, the expression of Ehcrt gene in E. histolytica trophozoites and add evidence that support CRT as a resident protein of the ER in E. histolytica species. The in vivo experiments suggest that CRT may play an important role during the early stages of the host-parasite relationship, when the parasite is adapting to a new environment, although the protein seems to be constitutively synthesized. Moreover, trophozoites apparently do not export EhCRT into the hepatic tissue in ALA.

  15. Ameliorative effect of two Ayurvedic herbs on experimentally induced arsenic toxicity in calves.

    Science.gov (United States)

    Biswas, Suman; Maji, Chinmoy; Sarkar, Prasanta Kumar; Sarkar, Samar; Chattopadhyay, Abichal; Mandal, Tapan Kumar

    2017-02-02

    Chronic arsenic poisoning due to contaminated subsoil water is a threat to society in West Bengal, India and in Bangladesh. The human being may also be affected by the exposed cattle from the affected area by consuming milk, egg, meat and others. In Ayurveda, several herbs like Haridra (turmeric), Shunthi (dried ginger root) and others are used for the management of arsenic poisoning. The study was conducted to find out the ameliorative effect of turmeric and ginger powder against experimentally induced arsenic toxicity in calves. Twenty four calves were divided into four groups (group I, II, III and IV) having six animals in each group. Animals of group I, II and III were orally administered with sodium arsenite at 1mg/kg body weight for 90 days and in addition group II and group III animals were treated orally with turmeric and ginger powder respectively at 10mg/kg body weight from 46th day onwards. Group IV animals were given food and water without drug and served as control. Arsenic content was estimated in faeces, hair, urine and plasma in every 15 days. Bio-chemical, haematological and anti-oxidant parameters were also assessed. Turmeric and ginger powder significantly (Parsenic levels through increased excretion via faeces and urine. Haemoglobin level, TEC and TLC were decreased in groups I, II and III, however these were improved significantly (Parsenic from the body but also give protection from possible damage caused by arsenic exposure, it may be concluded from the present study that turmeric and ginger can be helpful in the therapy of chronic arsenic toxicity in calves. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

    Science.gov (United States)

    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-05

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-11-01

    Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

  18. The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer

    Directory of Open Access Journals (Sweden)

    AL-Wajeeh NS

    2017-03-01

    Full Text Available Nahla Saeed Al-Wajeeh,1 Maryam Hajrezaie,1 Nawal Al-Henhena,1 Sareh Kamran,1 Elham Bagheri,1 Maryam Zahedifard,1 Kamelia Saremi,1 Suzita Mohd Noor,1 Hapipah Mohd Ali,2 Mahmood Ameen Abdulla11Department of Biomedical Science, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric’s homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the

  19. Efficacy of methylene blue in an experimental model of calcium channel blocker-induced shock.

    Science.gov (United States)

    Jang, David H; Donovan, Sean; Nelson, Lewis S; Bania, Theodore C; Hoffman, Robert S; Chu, Jason

    2015-04-01

    Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to

  20. Response of tundra plants to environmental variation during seven years of experimentally-induced permafrost thaw

    Science.gov (United States)

    Salmon, V. G.; Schuur, E.

    2016-12-01

    Seven years of warming at the Carbon in Permafrost Experimental Heating Research Project (CiPEHR) has induced dramatic environmental changes at this tussock tundra site. By 2015, soil-warmed plots thawed 35 cm more than controls and had significantly higher surface soil moisture during the growing season. Air warming using open top chambers significantly increased growing season air temperatures by 0.35°C. We examined 7 years of species-level leaf chemistry and total aboveground biomass in order to characterize the response of tundra plant species to varying environmental conditions. For this analysis, we used a multivariate framework that spanned treatments, combining principle component analysis of environmental covariates with linear mixed effect models. Overall, warm deep soils were associated with increased total aboveground biomass as well as increased inputs of litter N to surface soils. Both of these patterns were primarily driven by the tussock-forming sedge Eriophorum vaginatum. This species exhibited increased aboveground biomass and reduced nutrient resorption efficiency with permafrost thaw. Warm air temperatures at CiPEHR also increased total aboveground biomass but did not increase vascular foliar N pools or deciduous litter N pools, indicating little effect on plant-available N. Warm air temperatures may have exacerbated competition between vascular plant species, however. Leaf %N of E. vaginatum increased while Carex bigeloweii, Rubus chamaemorus, and Vaccinium uliginosum all exhibited decreased leaf %N. Warm and dry surface soil conditions were associated with decreased total aboveground biomass, vascular foliar N pools, and deciduous litter N pools. This negative relationship suggests that moisture limitation of decomposition can reduce plant-available N at this site. We found support for the theory that permafrost thaw alleviates N limitation of tundra plants but we emphasize the important roles that soil moisture, air temperature, and species

  1. Experimental observation of zinc dialkyl dithiophosphate (ZDDP)-induced iron sulphide formation

    Energy Technology Data Exchange (ETDEWEB)

    Soltanahmadi, Siavash, E-mail: s.soltanahmadi@leeds.ac.uk [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom); Morina, Ardian [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom); Eijk, Marcel C.P. van; Nedelcu, Ileana [SKF Engineering and Research Centre, 3430 DT Nieuwegein (Netherlands); Neville, Anne [Institute of Functional Surfaces, School of Mechanical Engineering, University of Leeds, LS2 9JT (United Kingdom)

    2017-08-31

    Graphical abstract: Chemical analysis of ZDDP-induced tribofilm under severe boundary lubricated regime in nano and micro-meter scales.▪ - Highlights: • A ZDDP-derived locally formed iron-sulphide layer is detected on the steel surface. • The iron-sulphide is a 5–10 nm thin distinct layer at steel-phosphate interface. • Near the surface-crack site the elemental distribution of the tribofilm is altered. • Sulphur concentration is enhanced in the iron-sulphide layer near the cracked-site. • ZDDP elements are detected inside the crack with a greater contribution of sulphur. - Abstract: Zinc dialkyl dithiophosphate (ZDDP) as a well-known anti-wear additive enhances the performance of the lubricant beyond its wear-protection action, through its anti-oxidant and Extreme Pressure (EP) functionality. In spite of over thirty years of research attempting to reveal the mechanism of action of ZDDP, there are still some uncertainties around the exact mechanisms of its action. This is especially the case with the role of sulphide layer formed in the tribofilm and its impact on surface fatigue. Although iron sulphide on the substrate is hypothesised in literature to form as a separate layer, there has been no concrete experimental observation on the distribution of the iron sulphide as a dispersed precipitate, distinct layer at the steel substrate or both. It remains to be clarified whether the iron sulphide layer homogeneously covers the surface or locally forms at the surface. In the current study a cross section of the specimen after experiment was prepared and has been investigated with Transmission Electron Microscopy (TEM) and Energy-Dispersive X-ray (EDX) elemental analysis. A 5–10 nm iron sulphide layer is visualised on the interface as a separate layer underneath the phosphate layer with an altered distribution of tribofilm elements near the crack site. The iron sulphide interface layer is more visible near the crack site where the concentration of the

  2. Arsenic-induced phosphate limitation under experimental Early Proterozoic oceanic conditions

    Science.gov (United States)

    Chi Fru, Ernest; Hemmingsson, Christoffer; Holm, Mikaela; Chiu, Beverly; Iñiguez, Enrique

    2016-01-01

    Comparison of phosphorus concentrations associated with modern hydrothermal Fe(III)(oxyhydr)oxides and ancient Fe(III) oxide-rich iron formations, is used to estimate bioavailable Precambrian marine phosphorus (P) concentrations. This led to the proposition of a low dissolved P budget of ∼10-25% of present-day levels, before ∼1.9 billion years ago. Estimates incorporating ancient marine Si levels ≥ 0.67 mM instead suggested global dissolved P levels greater than today. Here we unite current experimental models that have considered NaCl solutions containing elevated dissolved Fe(II), Si, Ca2+ and Mg2+ ions in the incorporation of P in Precambrian marine Fe(III)(oxyhydr)oxides, in addition to arsenic as a hydrothermal proxy. We show that the coprecipitation of dissolved P and Fe(III)(oxyhydr)oxides from arsenic-rich marine waters produces an average P distribution coefficient of ∼0.072 (± 0.01) μM-1. This is comparable to the ∼ 0.07 μM-1 predicted for Fe(III)(oxyhydr)oxides in modern arsenic-rich, submarine hydrothermal settings, from which the lower Early Proterozoic dissolved marine P concentrations were predicted. As/P molar ratios below modern seawater ratios removed the negative feedback effect high Si impose on P scavenging by Fe(III)(oxyhydr)oxides. The binding of As(III) to Fe(III)(oxyhydr)oxides exhibits a lower competitive influence on P fixation. As(V) that likely became prominent in the surficially oxidized Early Proterozoic oceans induced dissolved P limitation because of preferential P sequestration at the expense of dissolved As(V) enrichment. The control of As on P scavenging by the precipitating Fe(III)(oxyhydr)oxides is strong regardless of common seawater cations (Mg2+ and Ca2+). The data suggest that the application of Si and Fe(III)(oxyhydr)oxides as an ancient seawater P proxy should consider chemical variability between depositional basins, taking into account the rather strong role hydrothermal arsenic has on the distribution of P

  3. Changes in myoplasmic Ca2+ during fatigue differ between FDB fibers, between glibenclamide-exposed and Kir6.2-/- fibers and are further modulated by verapamil

    Science.gov (United States)

    Selvin, David; Renaud, Jean-Marc

    2015-01-01

    One objective of this study was to document how individual FDB muscle fibers depend on the myoprotection of KATP channels during fatigue. Verapamil, a CaV1.1 channel blocker, prevents large increases in unstimulated force during fatigue in KATP-channel-deficient muscles. A second objective was to determine if verapamil reduces unstimulated [Ca2+]i in KATP-channel-deficient fibers. We measured changes in myoplasmic [Ca2+] ([Ca2+]i) using two KATP-channel-deficient models: (1) a pharmacological approach exposing fibers to glibenclamide, a channel blocker, and (2) a genetic approach using fibers from null mice for the Kir6.2 gene. Fatigue was elicited with one tetanic contraction every sec for 3 min. For all conditions, large differences in fatigue kinetics were observed from fibers which had greater tetanic [Ca2+]i at the end than at the beginning of fatigue to fibers which eventually completely failed to release Ca2+ upon stimulation. Compared to control conditions, KATP-channel-deficient fibers had a greater proportion of fiber with large decreases in tetanic [Ca2+]i, fade and complete failure to release Ca2+ upon stimulation. There was, however, a group of KATP-channel-deficient fibers that had similar fatigue kinetics to those of the most fatigue-resistant control fibers. For the first time, differences in fatigue kinetics were observed between Kir6.2-/- and glibenclamide-exposed muscle fibers. Verapamil significantly reduced unstimulated and tetanic [Ca2+]i. It is concluded that not all fibers are dependent on the myoprotection of KATP channels and that the decrease in unstimulated force by verapamil reported in a previous studies in glibenclamide-exposed fibers is due to a reduction in Ca2+ load by reducing Ca2+ influx through CaV1.1 channels between and during contractions. PMID:25742954

  4. Stress-induced allodynia--evidence of increased pain sensitivity in healthy humans and patients with chronic pain after experimentally induced psychosocial stress.

    Directory of Open Access Journals (Sweden)

    Benjamin Crettaz

    Full Text Available BACKGROUND: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. METHODS: Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min and after (10 and 90 min inducing psychological stress with a standardized psychosocial stress test ("Trier Social Stress Test". RESULTS: Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. CONCLUSIONS: Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.

  5. Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Piotr Kuropka

    2017-01-01

    Full Text Available The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

  6. Experimental investigation of effects of jet decay rate on jet-induced pressures on a flat plate: Tabulated data

    Science.gov (United States)

    Kuhlman, J. M.; Ousterhout, D. S.; Warcup, R. W.

    1978-01-01

    Tabular data are presented for an experimental study of the effects of jet decay rate on the jet-induced pressure distribution on a flat plate for a single jet issuing at right angle to the flat plate into a uniform crossflow. The data are presented in four sections: (1) presents the static nozzle calibration data; (2) lists the plate surface static pressure data and integrated loads; (3) lists the jet centerline trajectory data; and (4) lists the centerline dynamic pressure data.

  7. 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.

  8. Black tea extract prevents lipopolysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis

    Directory of Open Access Journals (Sweden)

    Cho Sung-Bum

    2011-10-01

    Full Text Available Abstract Background Black tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE on lipopolysaccharide (LPS-induced NF-κB signaling in bone marrow derived-macrophages (BMM and determined the therapeutic efficacy of this extract on colon inflammation. Methods The effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA. The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores. Results LPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose polymerase (PARP in DSS-exposed mice was blocked by BTE. Conclusions These results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

  9. Verapamil does not modify catalytic activity of CYP450 in rainbow trout after long-term exposure.

    Science.gov (United States)

    Burkina, V; Zamaratskaia, G; Randak, T; Li, Z H; Fedorova, G; Pickova, J; Zlabek, V

    2012-05-01

    Little is known about the effects of the cardiovascular drug verapamil (VRP) on metabolic processes in fish. Most calcium channel blockers including VRP are metabolized by cytochrome P450 (CYP450) enzymes. In this study we investigated the in vivo effect of VRP on some CYP450-mediated reactions in juvenile rainbow trout (Oncorhynchus mykiss). Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg l(-1)) for 0, 21, and 42 day. The following CYP450-mediated reactions were studied in hepatic microsomes: O-dealkylation of ethoxyresorufin, methoxyresorufin, and pentoxyresorufin, hydroxylation of coumarin, tolbutamide, and p-nitrophenol, and O-debenzylation of 7-benzyloxy-4-trifluoromethylcoumarin. The amounts of products of these reactions did not differ among fish exposed to different levels of VRP and control fish. This suggests that the levels of VPR used did not alter catalytic activity of the selected CYP450 enzymes. In conclusion, none of the investigated CYP450-mediated reactions has potential as a biomarker to monitor VRP contamination of the aquatic environment. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance.

    Science.gov (United States)

    Hindenburg, A A; Baker, M A; Gleyzer, E; Stewart, V J; Case, N; Taub, R N

    1987-03-01

    We studied the intracellular distribution of drugs within anthracycline-sensitive and -resistant cells by computer-assisted digitized video fluorescence microscopy. We found that the antitumor antibiotic, daunorubicin, distributes differently in anthracycline-sensitive and -resistant human leukemia cells (HL-60). Verapamil and other agents known to circumvent resistance in pleiotropic drug-resistant cell lines were able to change the pattern of distribution of daunorubicin in the anthracycline-resistant HL-60 cells back to the distribution found in anthracycline-sensitive HL-60 cells. To investigate the biochemical basis for this effect, we studied the distribution of daunorubicin and doxorubicin in a hydrophobic/hydrophilic (membrane/cytoplasmic) environment using the two-compartment cell-free system of Folch. Our results demonstrate that various unrelated drugs known to overcome resistance will also change the distribution of the anthracyclines in the hydrophobic/hydrophilic compartments. Our data allow the hypothesis that various unrelated agents known to circumvent resistance may act by altering the hydrophobic/hydrophilic solubility of anthracyclines in the resistant cell.

  11. Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.

    Science.gov (United States)

    Li, Yongqiang; Abbaspour, Mohammadreza R; Grootendorst, Paul V; Rauth, Andrew M; Wu, Xiao Yu

    2015-08-01

    This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

    2014-01-01

    BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... controls of the S14761 effect in MCAO were performed as previously mentioned (n = 10) but with rats kept normothermic by a heating lamp for 22 hours. Finally, a meta-analysis of ipsapirone-induced hypothermia in man was included. RESULTS: Infarct volumes were reduced by 50% in hypothermic rats versus...... therapeutic hypothermia....

  13. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Schultz-Hector, S. (Institut fuer Strahlenbiologie, Neuherberg (Germany))

    1992-02-01

    Clinical and experimental heart irradiation can cause a variety of sequelae. A single dose of {>=} 15 Gy leads to a reversible exudative pericarditis, occurring in dogs, rabbits or rats at around 100 days. Its time-course is very similar in all species investigated, but there are considerable species and strain differences in severity and incidence. After longer, dose-dependent latency times chronic congestive myocardial failure develops. The paper reviews experimental data concerning dose response and pathogenesis. (author).

  14. 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

  15. Protective effect of Urtica dioica methanol extract against experimentally induced urinary calculi in rats

    National Research Council Canada - National Science Library

    ZHANG, HAIYING; LI, NING; LI, KUN; LI, PENG

    2014-01-01

    .... In the present study, a methanolic extract of aerial parts of Urtica dioica was screened for antiurolithiatic activity against ethylene glycol and ammonium chloride-induced calcium oxalate renal stones in male rats...

  16. Induced Voltage Self-Excitation for a Switched-Reluctance Generator. Experimental Verification of Concept

    National Research Council Canada - National Science Library

    Lipo, Thomas

    2000-01-01

    .... One means to excite the machine in a "self-starting" mode is to attach permanent magnets to the machine stator, so that rotor rotation will cause the magnet's field to induce electric current within...

  17. Protective effects of Aegle marmelos fruit pulp on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis.

    Science.gov (United States)

    Ghatule, Rohit R; Gautam, Manish K; Goel, Shalini; Singh, Amit; Joshi, Vinod K; Goel, Raj K

    2014-01-01

    Aegle marmelos (AM) fruit has been advocated in indigenous system of medicine for the treatment of various gastrointestinal disorders, fever, asthma, inflammations, febrile delirium, acute bronchitis, snakebite, epilepsy, leprosy, myalgia, smallpox, leucoderma, mental illnesses, sores, swelling, thirst, thyroid disorders, tumours and upper respiratory tract infections. The objective of this study was to study the curative effect of 50% ethanol extract of dried fruit pulp of AM (AME) against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. AME (200 mg/kg) was administered orally, once daily for 14 days after TNBS-induced colitis. Rats were given intracolonic normal saline or TNBS alone or TNBS plus oral AME. AME was studied for its in vitro antibacterial activity against Gram-negative intestinal bacteria and on TNBS-induced changes in colonic damage, weight and adhesions (macroscopic and microscopic), diarrhea, body weight and colonic levels of free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and pro-inflammatory marker (myeloperoxidase [MPO]) in rats. AME showed antibacterial activity against intestinal pathogens and decreased colonic mucosal damage and inflammation, diarrhea, colonic free radicals and MPO and enhanced body weight and colonic antioxidants level affected by TNBS. The effects of AME on the above parameters were comparable with sulfasalazine, a known colitis protective drug (100 mg/kg, oral). AME shows curative effects against TNBS-induced colitis by its antibacterial activity and promoting colonic antioxidants and reducing free radicals and MPO-induced colonic damage.

  18. Effect of the Angiotensin I Converting Enzyme Inhibitor, MK-421, on Experimentally Induced Drinking

    Science.gov (United States)

    Fregley, Melvin J.; Fater, Dennis C.; Greenleaf, John E.

    1982-01-01

    MK-421, the ethyl ester maleate salt of N-(S)-1-(ethoxycarbonyl)-3-phenyl-propyl- Ala-L-Pro, is an angiotensin I converting enzyme inhibitor. An initial objective was to determine whether MK-421, administered at 0, 2.5, 5.0, 10.0, 20.0 and 40.0 mg/kg, ip to 96 female rats 15 min prior to administration of the beta-adrenergic agonist, isoproterenol (25 microgram/kg, ip), would inhibit the drinking induced by isoproterenol during 2 h after its administration. The water intake induced by isoproterenol was inhibited significantly by 2.5 mg MK-421/kg. When a similar experiment was performed using Angiotensin I (AI) (200 microgram/kg, ip) as the dipsogenic agent, MK-421 (5 mg/kg, ip), administered 15 min prior to AI, inhibited significantly both the dipsogenic and the diuretic effect of AI. However, administration of angiotensin II (AII, 200 microgram/kg, ip) 15 min after MK-421 (5mg/kg) was accompanied by a water intake that did not differ from AII alone. The drink induced by ip administration of 1.0 m NaCl solution (1% of body wt, ip) was not inhibited by administration of MK-421 (5 mg/kg) 15 min prior to allowing access to water while the drink induced by a 24 h dehydration was partially inhibited. Thus, the drinks induced by administraition of either isoproterenol or AI are dependent on formation of AII. That induced by dehydration is partially dependent, while that induced by hypertonic siilinc is independent of the formation of AII.

  19. Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced by Mycobacterium bovis BCG▿

    Science.gov (United States)

    Souza, Mariana C.; Penido, Carmen; Costa, Maria F. S.; Henriques, Maria Graças

    2008-01-01

    Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 × 105 bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-γ). Accordingly, in vivo IL-2 or IFN-γ neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ. PMID:18809659

  20. Therapeutic effect of D-002 (abexol) on gastric ulcer induced experimentally in rats.

    Science.gov (United States)

    Molina, Vivian; Carbajal, Daisy; Arruzazabala, Lourdes; Más, Rosa

    2005-01-01

    D-002 is a mixture of higher aliphatic primary alcohols isolated from beeswax, wherein triacontanol is the most abundant alcohol, with antioxidant and anti-ulcer properties. Since compounds with cytoprotective and antioxidant effects can improve healing of gastroduodenal ulcer induced by noxious agents, this work investigated the healing effect of D- 002 on acute and chronic gastric ulcers induced with indomethacin and acetic acid, respectively, in rats. Acute gastric ulcer was induced with single oral doses of indomethacin (20 mg/kg). Treatments with D-002 at 50, 100, and 200 mg/kg or vehicle were administered 3 hours after ulcer induction. Three hours later, rats were sacrificed, and the stomach was removed for quantifying the lesions. Chronic gastric ulcer was induced by 50 microL of 80% acetic acid application on the anterior serosal surface of the glandular stomach during 20 seconds. Twenty-four hours later D-002 at 50, 100, and 200 mg/kg or vehicle was administered for 5 days. At the end of the treatment, animals were fasted for 24 hours and sacrificed, the stomachs were removed, and the lesions were quantified. D-002 orally administered at 100 and 200 mg/kg acutely significantly healed gastric ulcers induced with indomethacin by 39% and 56% compared with positive controls, respectively. Also, D-002 at 200 mg/kg, but not at 50 or 100 mg/kg, administered orally for 5 days after ulcer induction exerted a significant healing effect (65.8% inhibition) in gastric ulcers induced with acetic acid. In conclusion, this work demonstrated that D-002 administered after ulcer induction induced effective healing of acute and chronic gastric ulcers provoked by, respectively, indomethacin and acetic acid.

  1. Theoretical and experimental evaluation of effective stress-induced sorption capacity change and its influence on coal permeability

    Science.gov (United States)

    Li, Chengwu; Dong, Lihui; Xu, Xiaomeng; Hu, Po; Tian, Jianwei; Zhang, Yihuai; Yang, Leilei

    2017-06-01

    The gas sorption effect is an important factor affecting the gas permeability of a coal seam, which has been proved in many previous experimental measurements and analytical permeability studies. However, the sorption capacity of coal is usually not static due to the complexity of external stress variation and internal gas media features. The stress-induced sorption capacity variation and its effect on the coal permeability change have not been fully identified yet. Thus, in this paper we present a preliminary evaluation of the stress-induced sorption capacity change by introducing the adsorption capacity modified term, and an experiment is carried out to verify the influence of the altered effective stress on coal permeability. Langmuir-like adsorption deformation constant parameters were combined into the modified coal permeability model and were given values to fully estimate the influence on permeability caused by the modification term. We found that different change modes of effective stress would yield different change effects on the permeability, that is, with the same effective stress change amount, the altered external stress-induced change had less influence than the altered-pore pressure-induced change; however, both modes demonstrated that the model taking sorption capacity change into consideration is more consistent with the experimental data. The effect of sorption capacity change on coal permeability variation was also found to be tightly connected with the physical and mechanical properties of the coal itself. It is proved that considering stress-induced sorption ability change has a critical role in characterizing the permeability variation of coal.

  2. Evaluation of vaccination with Neospora caninum protein for prevention of fetal loss associated with experimentally induced neosporosis in sheep.

    Science.gov (United States)

    Jenkins, Mark C; Tuo, Wenbin; Dubey, J P

    2004-10-01

    To evaluate the immunologic response of a killed tachyzoite vaccine against Neospora caninum and its effectiveness in preventing fetal loss associated with experimentally induced neosporosis in sheep. 30 Dorset ewes. Ewes were randomly allocated to receive vaccination on days 1 and 60 of the study with a killed N caninum tachyzoite preparation in a commercially available adjuvant or a saline-adjuvant mixture. A ram was placed on pasture with the ewes from days 15 to 60. Blood was collected from ewes before primary and booster vaccinations and prior to experimental challenge with N caninum tachyzoite performed on day 90; sera were assessed via Neospora agglutination (NA) and immunofluorescence antibody (IFA) assays. Blood was collected from lambs before they suckled, and sera were tested for antibodies against N caninum. Of the 14 vaccinated ewes that became pregnant, 12 gave birth to live-born lambs; in contrast, 5 of 11 pregnant control ewes gave birth to live-born lambs. Whereas vaccination improved fetal survival in pregnant ewes challenged with N caninum tachyzoites, it did not appear to have any appreciable effect on transmission of N caninum to offspring, as indicated by results of NA and IFA assays. The N caninum tachyzoite vaccine used in this study appeared to provide protection against fetal loss associated with experimentally induced neosporosis in a high proportion of pregnant ewes.

  3. Experimental Study and Numerical Modeling of Wave Induced Pore Pressure Attenuation Inside a Rubble Mound Breakwater

    DEFF Research Database (Denmark)

    Troch, Peter; Rouck, Julien De; Burcharth, Hans Falk

    2003-01-01

    attenuation is studied using experimental data (in Section 2) and using a numerical wave flume (in Section 3). The experimental study includes the analysis of large scale data from a physical breakwater model and prototype data from the Zeebrugge breakwater. The large scale data are taken from literature...... and have been re-analysed in detail with respect to the attenuation characteristics. The analysis follows the method by Burcharth et al. (1999) and confirms the practical calculation method for the attenuation of the pore pressure in the core given in this reference. The attenuation of pore pressures...... in a breakwater core is also studied in the numerical wave flume VOFbreak. The numerical results are compared to the results from the experimental study....

  4. Visualization of Oxidative Stress Induced by Experimental Periodontitis in Keap1-Dependent Oxidative Stress Detector-Luciferase Mice.

    Science.gov (United States)

    Kataoka, Kota; Ekuni, Daisuke; Tomofuji, Takaaki; Irie, Koichiro; Kunitomo, Muneyoshi; Uchida, Yoko; Fukuhara, Daiki; Morita, Manabu

    2016-11-16

    The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days. The expressions of heme oxygenase-1 (HO-1) and malondialdehyde in periodontal tissue were significantly higher in the periodontitis group than in the control group. Immunofluorescent analysis confirmed that the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) occurred more frequently in the periodontitis group than in the control group. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the OKD-LUC model. Thus, the OKD-LUC mouse model may be useful for exploring the mechanism underlying the relationship between the Nrf2/antioxidant defense pathway and periodontitis by enabling the visualization of oxidative stress over time.

  5. [Static-dynamic MR urography. Comparison with excretory urography and scintigraphy in experimentally-induced urinary tract obstruction].

    Science.gov (United States)

    Rohrschneider, W K; Hoffend, J; Becker, K; Darge, K; Wunsch, R; Clorius, J H; Kooijman, H; Tröger, J

    2001-02-01

    To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction. Static-dynamic MRU--combination study with a respiratory-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA and furosemide--was obtained in comparison with 99mTc-MAG3 diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US) in 29 healthy piglets and in 20 piglets with surgically induced ureteric stenosis (total of 50 postoperative examination blocks). MRU allowed complete depiction of the urinary tract in all controls, in operated piglets the stenosis was always correctly identified. Quality of MRU was superior to EU in 36 of 43 comparative studies. Calculation of single kidney function from parenchymal renograms, and assessment of urinary excretion from whole-kidney renograms resulted in a highly significant agreement of MRU with DRS. Static-dynamic MR urography allows excellent depiction of experimentally induced urinary tract obstruction, 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 a functional-morphological correlation.

  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. Experimental characterization of a space charge induced modulation in high-brightness electron beam

    Directory of Open Access Journals (Sweden)

    T. Shaftan

    2004-08-01

    Full Text Available We present the experimental investigation of a collective effect driving strong modulation in the longitudinal phase space of a high-brightness electron beam. The measured beam energy spectrum was analyzed in order to reveal the main parameters of modulation. The experimental results were compared with a model of space-charge oscillations in the beam longitudinal phase space. The measurements and analysis allowed us to determine the range of the parameters of the observed effect on the modulation dynamics and illustrate its potential impact on short-wavelength free-electron laser performance.

  8. Efecto del verapamil sobre la resistencia de Plasmodium falciparum a Cloroquina

    OpenAIRE

    Moisés Wasserman; Jacqueline Chaparro

    2000-01-01

    La resistencia a cloroquina (CQ) es una de las principales causas de la recrudescencia de la malaria en el mundo; a pesar de que no se ha elucidado el mecanismo molecular de la cloroquino-resistencia, hay evidencia experimental que sugiere que el fenómeno está asociado con alteraciones en el transporte del medicamento. Aunque aun se debate si la resistencia de P. falciparum a CQ es producto de una rápida salid...

  9. Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

    Science.gov (United States)

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-04-01

    Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

  10. Targeting CYP450 modulation to decrease the risk of induced cataract in the experimental model

    Directory of Open Access Journals (Sweden)

    Patel D

    2010-01-01

    Full Text Available Background: Diabetes is one of the major causes of cataract. Some drugs prescribed for the treatment of diabetes are the modulators of CYP450, which may alter the risk of cataract. Objective: To study the effect of CYP450 modulation in galactosemic cataract. Materials and Methods: Male Sprague-Dawley suckling rats were allotted to four groups (n = 6, as follows: Group 1: Normal control, Group 2: Galactose control, Group 3: CYP450 inhibitor pretreated and Group 4: CYP450 inducer pretreated. Cataract was induced in animals of all groups except group 1 by feeding them galactose (50%, 21 days after parturition. From the eighteenth day of life, CYP450 inhibitor (nifedipine; 8.1 mg/kg and CYP450 inducer (pioglitazone; 3.8 mg/kg were given orally to groups 3 and 4, respectively. The maturation pattern of the cataract was observed by an operating microscope, every third day. Biochemical changes in the lenses of all groups, for example, CYP450 activity expressed as ΅M NADPH oxidized / unit time, alterations in the levels of total proteins, soluble proteins, and reduced glutathione (GSH following the induction of cataract, were estimated. Results: The microscopic examination of the lenses indicated that CYP450 inhibitor pre-treatment delayed (fourteenth day the occurrence of cataract, while CYP450 inducer pretreatment demonstrated an early (ninth day cataract as compared to galactose control rats (twelfth day. A significant decrease and increase in CYP450 activity was observed with the CYP450 inhibitor and inducer pre-treatment, respectively. There was no alteration in the GSH level, but a significant increase in total and soluble protein was found in groups 3 and 4 as compared to group 2. Conclusion: CYP450 may have a role in the initiation of cataract without any effect on the maturation pattern, as revealed by the delayed occurrence of cataract with the CYP450 inhibitor and an early onset of cataract with the CYP450 inducer.

  11. Experimental pain in human temporal muscle induced by hypertonic saline, potassium and acidity

    DEFF Research Database (Denmark)

    Jensen, K; Norup, M

    1992-01-01

    The study was aimed at developing a reference model for experimental pain and tenderness in the human temporal muscle by the local injection of hypertonic saline, potassium chloride and acidic phosphate buffer, using isotonic saline as control. The design was randomized and double-blind. Twenty...

  12. TLR3 Blockade in Rhinovirus-Induced Experimental Asthma Exacerbations: A Randomized Controlled Study

    NARCIS (Netherlands)

    Silkoff, Philip E.; Flavin, Susan; Gordon, Robert; Loza, Mathew J.; Sterk, Peter J.; Lutter, Rene; Diamant, Zuzana; Turner, Ronald B.; Lipworth, Brian J.; Proud, David; Singh, Dave; Eich, Andreas; Backer, Vibeke; Gern, James E.; Herzmann, Christian; Halperin, Scott A.; Mensinga, Tjeert T.; del Vecchio, Alfred M.; Branigan, Patrick; San Mateo, Lani; Baribaud, Frédéric; Barnathan, Elliot S.; Johnston, Sebastian L.

    2017-01-01

    Human rhinoviruses (HRV) commonly precipitate asthma exacerbations. TLR3, an innate pattern-recognition receptor, is triggered by HRV driving inflammation that may worsen asthma. To evaluate an inhibitory monoclonal antibody to TLR3, CNTO3157, on experimental HRV-16 inoculation in healthy and

  13. 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.

  14. The relationship between plasma free fatty acids and experimentally induced hepatic encephalopathy in the rat

    NARCIS (Netherlands)

    Smit, J. J.; Bosman, D. K.; Jörning, G. G.; de Haan, J. G.; Maas, M. A.; Chamuleau, R. A.

    1991-01-01

    Two experimental models of hepatic encephalopathy in the rat have been investigated in order to study the postulated relationship between plasma free fatty acids concentration (C6 - C22:0) and the degree of hepatic encephalopathy. As a model of chronic hepatic encephalopathy, porta caval shunted

  15. The impact of dietary induced hyperparathyroidism on healthy and diseased periodontia: an experimental study in rats.

    Science.gov (United States)

    Lütfioğlu, Müge; Sakallioğlu, Umur; Sakallioğlu, Elif Eser; Bariş, Sancar; Gürgör, Pınar

    2012-03-01

    Nutrition may be a potential modifying factor in periodontal conditions. The present study investigated this phenomenon for dietary induced hyperparathyroidism (dHPT) by revealing the histopathological and histomorphometrical profiles of healthy and diseased periodontia in dHPT. Dietary induced hyperparathyroidism was induced in 12 rats by dietary calcium/phosphorous imbalance and 12 rats were fed standard diet (SD). Periodontitis was induced on the right mandibular molar teeth (mmt) of these rats by injecting an endotoxin + saline solution whereas injecting pure saline to the left mmt. Thus, four study groups were created: dHPT + saline (group 1), dHPT + endotoxin (group 2), SD + endotoxin (group 3) and SD + saline (group 4). Histological sections were obtained from the second mmt and examined using light microscope. Group 1 demonstrated inflammatory and degenerative alterations in periodontium without pocket formation. Periodontitis was evident in groups 2 and 3. Group 2 revealed the highest amounts of gingival inflammatory cell and vessel counts (group 2 > group 3 > group 1 > group 4), attachment and bone losses (group 2 > group 3 > groups 1 > group 4) and osteoclast count (group 2 > group 3 > group 1 > group 4) (p < 0.05). These results propose that dHPT may impair the health status of periodontium and may worsen the pathobiology of periodontal diseases. © 2011 John Wiley & Sons A/S.

  16. 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

  17. Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

    Science.gov (United States)

    Constantinescu, Mihaela Ioana; Constantinescu, Dan Petru; Andercou, Aurel; Mironiuc, Ion Aurel

    2013-01-01

    Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH

  18. Experimental study and simulation of the residual activity induced by high-energy argon ions in copper

    Science.gov (United States)

    Strašík, I.; Mustafin, E.; Seidl, T.; Pavlovič, M.

    2010-03-01

    The paper presents new experimental results and FLUKA-simulations of residual activation induced by high-energy argon ions in copper. It follows the previous residual activation studies performed at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt with uranium ions as a preparatory work for constructing the FAIR facility. Copper samples were irradiated by 1 GeV/u and 500 MeV/u 40Ar ions and investigated by gamma-ray spectroscopy. The samples were irradiated in the stacked-foil geometry. The isotopes with dominating contribution to the total residual activity were identified and their partial activities were quantified. Depth-profiling of the partial residual activities of all identified isotopes was performed by measurements of individual target foils. The experimental results were compared with simulations by the FLUKA-code. A satisfactory agreement between the experiment and the simulations was observed.

  19. Numerical and Experimental Evaluation of High-Intensity Focused Ultrasound-Induced Lesions in Liver Tissue Ex Vivo.

    Science.gov (United States)

    Haddadi, Samaneh; Ahmadian, Mohammad Taghi

    2017-11-30

    Recent advances in the field of acoustics and piezoelectric and ultrasound transducers have led to new approaches to the diagnosis and treatment of certain diseases. One method of treatment with ultrasonic waves is high-intensity focused ultrasound (HIFU) treatment, which is a thermal therapeutic method used to treat malignant tumors. Although a variety of treatment-planning strategies using ultrasonic waves have been investigated, little clinical success has been achieved. Computational modeling is a powerful tool for predicting device performance. The heating induced by a concave transducer with operating powers of 85 and 135 W was studied, and the experimental results presented in this article verify its applicability. Numerical simulations of the nonlinear acoustic field were performed by using the Westervelt and Khokhlov-Zabolotskaya-Kuznetsov equations. Heat transfer was measured for the 2 operational powers, and the results were compared with ex vivo experimental results. In addition, thermal dose contours for both the simulation and experimental results were calculated to investigate the ablated area. Good agreement was found between the experimental and numerical results. The results show that the average temperature deviations calculated at the focal point were 12.8% and 4.3% for transducer powers of 85 and 135 W, respectively. This study provides guidance to HIFU practitioners in determining lesion size and identifying nonlinear effects that should be considered in HIFU procedures. © 2017 by the American Institute of Ultrasound in Medicine.

  20. Preliminary studies on the effect of rebamipide against the trypsin and egg-albumin induced experimental model of asthma.

    Science.gov (United States)

    Gohil, Priyanshee; Thakkar, Himani; Gohil, Unnati; Deshpande, Shrikalp

    2011-12-01

    The present investigation was carried out to study the effect of rebamipide in experimentally induced bronchial asthma in mice. Trypsin and egg-albumin induced chronic model of asthma was used and various parameters were measured on the 35th day. The asthmatic control group showed lower level of haemoglobin saturation with oxygen, tidal volume, airflow rate and higher respiratory rate, serum bicarbonate level, eosinophil count in bronchoalveolar lavage fluid and histamine level compared to the normal control group. Dexamethasone and rebamipide treated groups showed the return of all the above parameters towards normal values. Histopathological examination of lungs showed more prominent alveolar and muscular layer destruction in the asthmatic control group than in dexamethasone and rebamipide treated groups. Rebamipide showed a beneficial effect and might be used for the treatment of bronchial asthma.

  1. Experimental and theoretical investigation of a self-absorbed spectral line emitted from laser-induced plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Ben Ahmed, Jalloul; Cowpe, John

    2010-06-20

    Using well-known expressions describing radiative transfer, we have established an expression predicting the spectral profile of a self-absorbed Ca{sup ++}393.4 nm emission line as emitted by a transient laser-induced plasma. In this approach, the plasma was approximated as comprising five distinct layers, each of thickness 0.5 mm, and each characterized by a unique uniform electron density, electron temperature, and optical depth. The validity of the theoretical model was confirmed by successful comparison with experimental data. Inhomogeneous laser-induced plasmas were produced on the surface of an aqueous CaCl2 (0.01 mol/l) solution using a frequency-doubled Nd:YAG laser. Optical emission spectra were collected in such a way as to allow for temporal and spatial diagnostics of the plasma plumes.

  2. Experimental investigation of effect of jet decay rate on jet-induced pressures on a flat plate

    Science.gov (United States)

    Kuhlman, J. M.; Ousterhout, D. S.; Warcup, R. W.

    1978-01-01

    An experimental study of the interaction between a lift jet and an aircraft wing for a jet VTOL aircraft was performed for the simplified model of an unheated, subsonic, circular jet exiting at right angles to a flat plate into a uniform subsonic crosswind. The effects of jet dynamic pressure decay rate upon the jet location and jet induced pressure distribution on the plate were studied over a range of jet to crossflow velocity ratios of 2.2 or = R or = 10. Jet decay rate was varied through use of cylindrical centerbodies with flat or hemispherical tips submerged in the jet nozzle at various depths below the jet exit plane. Quicker jet dynamic pressure decay, caused by the presence of a centerbody, resulted in reductions in the jet induced lift loss by as much as 45 percent relative to values for jets with no centerbody. These reductions in lift loss were observed at the larger values of crossflow velocity.

  3. Determination of micronutrients and oxidative stress status in the blood of STZ-induced experimental diabetic rat models.

    Science.gov (United States)

    Ragbetli, Cennet; Dede, Semiha; Tanritanir, Pinar; Yoruk, Ibrahim Hakki; Ragbetli, Murat Cetin

    2014-11-01

    This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3-4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p micronutrients were affected significantly.

  4. 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

  5. Urolithin A Mitigates Cisplatin-Induced Nephrotoxicity by Inhibiting Renal Inflammation and Apoptosis in an Experimental Rat Model.

    Science.gov (United States)

    Guada, Melissa; Ganugula, Raghu; Vadhanam, Manicka; Ravi Kumar, Majeti N V

    2017-10-01

    Cumulative kidney toxicity associated with cisplatin is severe and there is no clear consensus on the therapeutic management of the same. The pathogenesis involves activation of inflammatory and apoptotic pathways; therefore, regulating these pathways offers protection. Given the anti-inflammatory and antioxidant effects of urolithin A, a gut microbial metabolite of ellagic acid, our aim was to explore the potential use of urolithin A in the prevention of cisplatin-induced nephrotoxicity in an experimental rat model. For this purpose, animals received a single intraperitoneal dose of cisplatin (5 mg/kg body weight). Six hours prior to cisplatin administration, rats were orally treated with either ellagic acid or urolithin A (50 mg/kg body weight), followed by a daily dose of these compounds during the next 5 days. At the end, plasma and kidneys were collected for analysis. Cisplatin-induced kidney damage was revealed by a significant rise in the plasma creatinine levels accompanied by significant morphologic changes in tubules, T cell Ig and mucin domain-containing protein-1, ionized calcium-binding adapter molecule 1, as well as a marked increase in the number of apoptotic cells localized in tubules. Cisplatin also reduced nitric oxide synthase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells resulting in regulation of various inflammatory cytokines. Urolithin A effectively attenuated cisplatin-induced kidney damage and showed significantly greater effect than its precursor ellagic acid on preserving the normal kidney architecture by downregulating the proinflammatory cytokines. In summary, urolithin A mitigates cisplatin-induced nephrotoxicity in rats by modulation of the inflammatory cascade and inhibition of the proapoptotic pathway. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Histopathological and immunohistochemical study of the hepatic lesions experimentally induced by Entamoeba dispar

    Directory of Open Access Journals (Sweden)

    C. A. X. Costa

    2010-08-01

    Full Text Available The sequence of hepatic necrotic-inflammatory events produced by Entamoeba dispar are originally described in this work. For the first time were described in details the experimental lesions produced by E. dispar, as well as the distribution of the trophozoites detected by the immunohistochemistry. Animals experimentally infected with E. dispar presented necrosis, thrombosis and chronic granulomatous inflammation. Immunoreactive products derived from trofozoites were observed close or associated with trophozoites, epithelioid cells, leucocytes and hepatocytes. Few are the articles on the literature about virulence of E. dispar, which is approximately 9 times more frequent than to E. histolytica. Variation in the virulence is, therefore expected and signalizing the need of the continuity of studies with E. dispar strains from different places in the world. Taking into account that E. dispar is a closely related species to E. histolytica, these studies could determine new elements involved with E. histolytica pathogenesis, helping us to understand better the disease.

  7. Histopathological and immunohistochemical study of the hepatic lesions experimentally induced by Entamoeba dispar.

    Science.gov (United States)

    Costa, C A X; De Brito, K N O; Gomes, M A; Caliari, M V

    2010-08-26

    The sequence of hepatic necrotic-inflammatory events produced by Entamoeba dispar are originally described in this work. For the first time were described in details the experimental lesions produced by E. dispar, as well as the distribution of the trophozoites detected by the immunohistochemistry. Animals experimentally infected with E. dispar presented necrosis, thrombosis and chronic granulomatous inflammation. Immunoreactive products derived from trofozoites were observed close or associated with trophozoites, epithelioid cells, leucocytes and hepatocytes. Few are the articles on the literature about virulence of E. dispar, which is approximately 9 times more frequent than to E. histolytica. Variation in the virulence is, therefore expected and signalizing the need of the continuity of studies with E. dispar strains from different places in the world. Taking into account that E. dispar is a closely related species to E. histolytica, these studies could determine new elements involved with E. histolytica pathogenesis, helping us to understand better the disease.

  8. Bite marks in mink—Induced experimentally and as reflection of aggressive encounters between mink

    DEFF Research Database (Denmark)

    Hansen, Steffen W; Møller, Steen Henrik; Damgaard, Birthe Marie

    2014-01-01

    tFor many years, bite marks have been used as an indicator for aggression in mink productionsystems. However, the validity of bite marks as indicator of aggression has recently beenquestioned. We therefore tested the following hypotheses: (1) experimentally applied pressure to, or penetration of......, the pelt during the growth phase of the winter coat will producemarks that can be recognized as bite marks at pelting, (2) bite marks applied experimentally by use of an artificial tooth or occurring due to social/aggressive interactions (bites)between mink are only visible if pressure/bite on the mink...... skin is applied during the activegrowth phase of the winter coat prior to time when matured, (3) bite marks will be easierto detect on dark mink than on mink with light coloured fur and (4) the number of bitemarks accumulates and increases with time mink are housed in groups. The experimentalmink were...

  9. Diet-induced expansion of pathobionts in experimental colitis: Implications for tailored therapies

    OpenAIRE

    Devkota, Suzanne; Chang, Eugene B.

    2013-01-01

    Evidence presented in our recent study and elsewhere suggests that the interplay of dietary macronutrients with the intestinal lumen alters the microbial environment, and thus host-microbe interactions, in ways that are not always in a favorable, mutualistic fashion. Specifically, in inflammatory bowel diseases (IBD), experimental and clinical observations have implicated a detrimental impact of environmental/microbial factors on the etiopathogenesis of IBD in individuals with a background of...

  10. Experimentally induced peri-implant mucositis. A clinical study in humans.

    Science.gov (United States)

    Pontoriero, R; Tonelli, M P; Carnevale, G; Mombelli, A; Nyman, S R; Lang, N P

    1994-12-01

    The purpose of this study was to compare the clinical and microbiological (microscopic) parameters during the development of experimental gingivitis and experimental peri-implant mucositis. Twenty partially edentulous patients were treated for moderate to advanced periodontal disease. Following active periodontal therapy consisting of motivation, instruction in oral hygiene practices, scaling and root planing and periodontal surgery where indicated, IMZ oral implants were incorporated in posterior edentulous areas. After 3 months of healing, the prosthetic abutments were connected, and the patients were closely supervised for another 2 months of healing. At this time, baseline data were obtained. Re-examinations were scheduled at 3 and 6 months. Following this, the patients were asked to refrain from oral hygiene practices for 3 weeks. At all examinations including the end of the period of no oral hygiene, the following clinical parameters were obtained: Plaque Index, Gingival Index and Sulcus Bleeding Index, all modified by Mombelli et al. (1987), probing pocket depths and recession in mm. Furthermore, submucosal/subgingival plaque samples were obtained and analyzed using phase contrast microscopy. At the end of the 3-week period of plaque accumulation, optimal oral hygiene was reinstituted. There were no statistically significant differences between the mean values of all parameters at implant compared to tooth sites at any observation periods. The period of no oral hygiene demonstrated a similar cause-effect relationship between the accumulation of bacterial plaque and the development of peri-implant mucositis as established for the gingival units by the experimental gingivitis model.

  11. Experimental investigation on dynamic characteristics and strengthening mechanism of laser-induced cavitation bubbles.

    Science.gov (United States)

    Ren, X D; He, H; Tong, Y Q; Ren, Y P; Yuan, S Q; Liu, R; Zuo, C Y; Wu, K; Sui, S; Wang, D S

    2016-09-01

    The dynamic features of nanosecond laser-induced cavitation bubbles near the light alloy boundary were investigated with the high-speed photography. The shock-waves and the dynamic characteristics of the cavitation bubbles generated by the laser were detected using the hydrophone. The dynamic features and strengthening mechanism of cavitation bubbles were studied. The strengthening mechanisms of cavitation bubble were discussed when the relative distance parameter γ was within the range of 0.5-2.5. It showed that the strengthening mechanisms caused by liquid jet or shock-waves depended on γ much. The research results provided a new strengthening method based on laser-induced cavitation shotless peening (CSP). Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antidiarrheal activity of Pterocarpus erinaceus methanol leaf extract in experimentally-induced diarrhea.

    Science.gov (United States)

    Ezeja, I Maxwell; Ezeigbo, Ihechiluru I; Madubuike, Kelechi G; Udeh, Nkiru E; Ukweni, Iheanacho A; Akomas, Stella C; Ifenkwe, Daniel C

    2012-02-01

    To investigate the antidiarrheal activity of the methanol leaf extract of Pterocarpus erinaceus in vivo. The methanol leaf extract of Pterocarpus erinaceus was evaluated using different doses (100, 200 and 400 mg/kg body weight) orally for antidiarrheal activity using castor oil-induced diarrhea, charcoal meal transit time and castor oil-induced enteropooling in different groups of albino Wistar mice. The activity of the extract at different doses were compared to diphenoxylate (5 mg/kg) and atropine sulphate (3 mg/kg) which were used as standard reference drugs and also to the distilled water administered negative control group of mice. The extract at the doses used caused a significant (PPterocarpus erinaceus extract produced significant antidiarrheal activity and the action may attribute to inhibition of gastrointestinal movement and fluid secretion. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. Numerical and Experimental Study on Negative Buoyance Induced Vortices in N-Butane Jet Flames

    KAUST Repository

    Xiong, Yuan

    2015-07-26

    Near nozzle flow field in flickering n-butane diffusion jet flames was investigated with a special focus on transient flow patterns of negative buoyance induced vortices. The flow structures were obtained through Mie scattering imaging with seed particles in a fuel stream using continuous-wave (CW) Argon-ion laser. Velocity fields were also quantified with particle mage velocimetry (PIV) system having kHz repetition rate. The results showed that the dynamic motion of negative buoyance induced vortices near the nozzle exit was coupled strongly with a flame flickering instability. Typically during the flame flickering, the negative buoyant vortices oscillated at the flickering frequency. The vortices were distorted by the flickering motion and exhibited complicated transient vortical patterns, such as tilting and stretching. Numerical simulations were also implemented based on an open source C++ package, LaminarSMOKE, for further validations.

  14. A review of the evidence regarding associations between attachment theory and experimentally induced pain.

    Science.gov (United States)

    Meredith, Pamela Joy

    2013-04-01

    Theoretical and empirical evidence suggests that adult attachment and pain-related variables are predictably and consistently linked, and that understanding these links may guide pain intervention and prevention efforts. In general, insecure attachment has been portrayed as a risk factor, and secure attachment as a protective factor, for people with chronic pain conditions. In an effort to better understand the relationships among attachment and pain variables, these links have been investigated in pain-free samples using induced-pain techniques. The present paper reviews the available research linking adult attachment and laboratory-induced pain. While the diverse nature of the studies precludes definitive conclusions, together these papers offer support for associations between insecure attachment and a more negative pain experience. The evidence presented in this review highlights areas for further empirical attention, as well as providing some guidance for clinicians who may wish to employ preventive approaches and other interventions informed by attachment theory.

  15. Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Francis Lopes Pacagnelli

    2016-01-01

    Full Text Available Abstract Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8 and monocrotaline-induced pulmonary arterial hypertension (M; n = 8. Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test, and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05. Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05. Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

  16. α-adrenergic agonist brimonidine control of experimentally induced myopia in guinea pigs: A pilot study

    Science.gov (United States)

    Liu, Yan; Wang, Yuexin; Lv, Huibin; Jiang, Xiaodan; Zhang, Mingzhou

    2017-01-01

    Purpose To investigate the efficacy of α-adrenergic agonist brimonidine either alone or combined with pirenzepine for inhibiting progressing myopia in guinea pig lens–myopia-induced models. Methods Thirty-six guinea pigs were randomly divided into six groups: Group A received 2% pirenzepine, Group B received 0.2% brimonidine, Group C received 0.1% brimonidine, Group D received 2% pirenzepine + 0.2% brimonidine, Group E received 2% pirenzepine + 0.1% brimonidine, and Group F received the medium. Myopia was induced in the right eyes of all guinea pigs using polymethyl methacrylate (PMMA) lenses for 3 weeks. Eye drops were administered accordingly. Intraocular pressure was measured every day. Refractive error and axial length measurements were performed once a week. The enucleated eyeballs were removed for hematoxylin and eosin (H&E) and Van Gieson (VG) staining at the end of the study. Results The lens-induced myopia model was established after 3 weeks. Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone was capable of inhibiting progressing myopia, as shown by the better refractive error (p=0.024; p=0.006) and shorter axial length (p=0.005; p=0.0017). Treatment with 0.1% brimonidine and 0.2% brimonidine combined with 2% pirenzepine was also effective in suppressing progressing refractive error (p=0.016; p=0.0006) and axial length (p=0.017; p=0.0004). The thickness of the sclera was kept stable in all groups except group F; the sclera was much thinner in the lens-induced myopia eyes compared to the control eyes. Conclusions Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone, as well as combined with 2% pirenzepine, was effective in inhibiting progressing myopia. The result indicates that intraocular pressure elevation is possibly a promising mechanism and potential treatment for progressing myopia. PMID:29204068

  17. Experimental evidence of new tetragonal polymorphs of silicon formed through ultrafast laser-induced confined microexplosion

    OpenAIRE

    Rapp, L.; Haberl, B.; Pickard, C. J.; J.E. Bradby; Gamaly, E. G.; Williams, J.S.; Rode, A. V.

    2015-01-01

    Ordinary materials can transform into novel phases at extraordinary high pressure and temperature. The recently developed method of ultrashort laser-induced confined microexplosions initiates a non-equilibrium disordered plasma state. Ultra-high quenching rates overcome kinetic barriers to the formation of new metastable phases, which are preserved in the surrounding pristine crystal for subsequent exploitation. Here we demonstrate that confined microexplosions in silicon produce several meta...

  18. Experimental investigation of lateral forces induced by flow through model labyrinth glands

    Science.gov (United States)

    Leong, Y. M. M. S.; Brown, R. D.

    1984-01-01

    The lateral forces induced by flow through model labyrinth glands were investigated. Circumferential pressure distributions, lateral forces and stiffness coefficients data obtained are discussed. The force system is represented as a negative spring and a tangential force orthogonal to eccentricity. The magnitude of these forces are dependent on eccentricity, entry swirl, rotor peripheral velocity and seal size. A pressure equalization chamber at midgland tests should in significantly reduced forces and stiffness coefficients.

  19. Reversal of haloperidol-induced orofacial dyskinesia by Murraya koenigii leaves in experimental animals.

    Science.gov (United States)

    Patil, Rupali; Hiray, Yogesh; Shinde, Sandesh; Langade, Padmaja

    2012-06-01

    Orofacial dyskinesia (OD) is a late complication of prolonged neuroleptic treatment characterized by involuntary movements of the oral region. Chronic treatment with neuroleptics leads to development of vacuous chewing movements (VCMs). VCMs in rats are widely accepted as an animal model of OD. To study the effect of Murraya koenigii L. (Rutaceae) leaves on haloperidol-induced OD. Effect of alcohol extract of M. koenigii leaves (EEMK) and its alkaloid fraction (AMK) on body weight, locomotor activity, behavioral parameters, such as VCMs, tongue protrusions (TPs), orofacial bursts (OBs), and biochemical parameters such as antioxidant defense enzymes levels [superoxide dismutase (SOD) and catalase (CAT)], glutathione (GSH) levels, and lipid peroxidation (LPO) in the forebrain region was studied in haloperidol-treated rats. Rats chronically treated with haloperidol (1 mg/kg, i.p., 21 days) significantly decreased locomotion and developed VCMs, OBs, and TPs. Biochemical analysis reveals that chronic haloperidol-treated rats also showed decreased levels of SOD and CAT. Chronic haloperidol treatment significantly induced LPO and decreased the forebrain GSH levels in the rats. Co-administration of EEMK (100 and 300 mg/kg, p.o.) and AMK (30 and 100 mg/kg, p.o.) along with haloperidol significantly reversed the effect on locomotion. EEMK and AMK significantly reversed the haloperidol-induced decrease in forebrain SOD and CAT levels in rats and significantly reduced the LPO and restored the decreased GSH levels by chronic haloperidol treatment. The study concludes that M. koenigii could be screened as a potential drug for the prevention or treatment of neuroleptic-induced OD.

  20. Neural circuitry mediating inflammation-induced central pain amplification in human experimental endotoxemia.

    Science.gov (United States)

    Benson, Sven; Rebernik, Laura; Wegner, Alexander; Kleine-Borgmann, Julian; Engler, Harald; Schlamann, Marc; Forsting, Michael; Schedlowski, Manfred; Elsenbruch, Sigrid

    2015-08-01

    To elucidate the brain mechanisms underlying inflammation-induced visceral hyperalgesia in humans, in this functional magnetic resonance imaging (fMRI) study we tested if intravenous administration of lipopolysaccharide (LPS) involves altered central processing of visceral pain stimuli. In this randomized, double-blind, placebo-controlled fMRI study, 26 healthy male subjects received either an intravenous injection of low-dose LPS (N=14, 0.4 ng/kg body weight) or placebo (N=12, control group). Plasma cytokines (TNF-α, IL-6), body temperature, plasma cortisol and mood were assessed at baseline and up to 6 h post-injection. At baseline and 2 h post-injection (test), rectal pain thresholds and painful rectal distension-induced blood oxygen level-dependent (BOLD) responses in brain regions-of-interest were assessed. To address specificity for visceral pain, BOLD responses to non-painful rectal distensions and painful somatic stimuli (i.e., punctuate mechanical stimulation) were also analyzed as control stimuli. Compared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-α, IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced up-regulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all FWE-corrected ppain-induced neural activation in DLPFC and aMCC. No significant LPS effects were observed on neural responses to non-painful rectal distensions or mechanical stimulation. These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Lipid therapy with two agents in ropivacaine-induced toxicity: experimental study in swine

    OpenAIRE

    Matheus Rodrigues Bonfim; Marcos De Simone Melo; Elisabeth Dreyer; Luís Fernando Affini Borsoi; Thales Gê de Oliveira; Artur Udelsmann

    2012-01-01

    BACKGROUND AND OBJECTIVE: Compare hemodynamic changes after ropivacaine-induced toxicity followed by treatment with two lipid emulsions in swine. METHODS: Large White pigs were anesthetized with thiopental, followed by intubation, and kept on mechanical ventilation. Hemodynamic variables at rest were recorded with invasive pressure monitoring and pulmonary artery catheterization. After 30 minutes, 7 mg.kg-1 ropivacaine were injected intravenously and new hemodynamic measurements were performe...

  2. Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats.

    Science.gov (United States)

    Pacagnelli, Francis Lopes; Sabela, Ana Karênina Dias de Almeida; Mariano, Thaoan Bruno; Ozaki, Guilherme Akio Tamura; Castoldi, Robson Chacon; Carmo, Edna Maria do; Carvalho, Robson Francisco; Tomasi, Loreta Casquel; Okoshi, Katashi; Vanderlei, Luiz Carlos Marques

    2016-07-01

    Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

  3. Geraniol attenuates oxidative stress by Nrf2 activation in diet-induced experimental atherosclerosis.

    Science.gov (United States)

    Jayachandran, Muthukumaran; Chandrasekaran, Balaji; Namasivayam, Nalini

    2015-07-01

    Preclinical and clinical studies suggest the use of antioxidants as an effective measure to reduce the progression of oxidative-stress-related disorders. Nuclear factor E2-related factor 2 (Nrf2) is a key component to cellular redox homeostasis in the attenuation of oxidative-stress-associated pathological processes. The objective of the current study was to evaluate the role of geraniol (GOH) in preserving the plasma lipid status, endothelial function, antioxidant status, and inhibition of lipid peroxidation (LPO) in hamsters fed an atherogenic diet (AD). Male Syrian hamsters were randomly grouped into four groups: group 1 was control animals; group 2 was animals fed GOH alone (100 mg/kg bw po); group 3 was animals fed AD (standard pellet diet+10% coconut oil+0.25% cholesterol+0.25% cholic acid); and group 4 was fed AD+GOH (100 mg/kg bw) for 12 weeks. At the end of the feeding period, the animals were sacrificed and the liver, heart, and aorta from each group were analyzed for antioxidants, LPO markers, and histological changes. AD feeding induced a significant change in lipid profile, endothelial function marker, activities of the antioxidant enzymes, alterations in the LPO markers, Nrf2 expression, and equally significant changes in the organ histology. Supplementation with GOH appreciably prevented the alterations induced by the AD on all the above parameters. Thus, GOH offers marked protection against AD-induced abnormalities.

  4. Effect of Concentrated Apple Extract on Experimental Colitis Induced by Acetic Acid.

    Science.gov (United States)

    Pastrelo, Maurício Mercaldi; Dias Ribeiro, Carla Caroline; Duarte, Joselmo Willamys; Bioago Gollücke, Andréa Pitelli; Artigiani-Neto, Ricardo; Ribeiro, Daniel Araki; Miszputen, Sender Jankiel; Fujiyama Oshima, Celina Tizuko; Ribeiro Paiotti, Ana Paula

    2017-01-01

    Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1-Sham/saline solution, G2-CAE/control, G3-acetic acid/control, G4-curative- CAE treatment and G5-preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

  5. Therapeutic effect of coenzyme Q10 against experimentally-induced hepatocellular carcinoma in rats.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-01-01

    The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Evaluation of hepatoprotective potential of Erythrina indica leaves against antitubercular drugs induced hepatotoxicity in experimental rats.

    Science.gov (United States)

    Mujahid, Mohd; Hussain, Talib; Siddiqui, Hefazat Hussain; Hussain, Arshad

    Erythrina indica Lam. traditionally used in the treatment of laxative, diuretic, worm infestation, liver ailment and joints pain. To evaluate the antihepatotoxic potential of Erythrina indica against isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in rats. Liver toxicity was induced by antitubercular drugs (INH+ RIF) at dose level of 50 mg/kg each, p.o for 28 days. 50% methanolic extract of Erythrina indica (100 and 200 mg/kg) were administered orally once daily for 28 days. The hepatoprotective activity was assessed using various biochemical parameters SGOT, SGPT, ALP, bilirubin, total protein, albumin and LDH. Meanwhile, in vivo antioxidant activities as SOD, CAT, GSH and, LPO were measured in liver homogenate also histological examinations were carried out to assess hepatoprotective activity. The values were subjected to one way analysis of variance (ANOVA) followed by Tukey multiple compare test. Results were considered statistically significant when P indica (E. indica) significantly prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, Erythrina indica significantly reduced the lipid peroxidation (P indica attenuated the hepatocellular necrosis, regeneration and repair of cells toward normal. The results of this study strongly indicate the protective effect of Erythrina indica against liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  7. Azadirachta indica Attenuates Colonic Mucosal Damage in Experimental Colitis Induced by Trinitrobenzene Sulfonic Acid.

    Science.gov (United States)

    Gautam, M K; Goel, Shalini; Ghatule, R R; Singh, A; Joshi, V K; Goel, R K

    2013-09-01

    Azadirachta indica leaves indicated the presence of active principles with proven antioxidants, antiinflammatory, immunomodulatory, free radical scavenging and healing properties. In the present study we evaluated the healing effects of 50% ethanol extract of dried leaves of Azadirachta indica on trinitrobenzene sulfonic acid-induced colitis in rats. Azadirachta indica extract (500 mg/kg) was administered orally, once daily for 14 days and studied for its effects on diarrhoea, food and water intake, body weight changes, colonic damage and inflammation, histology, antibacterial activity and free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase activities in colonic tissue. Intracolonic trinitrobenzene sulfonic acid increased colonic mucosal damage and inflammation, diarrhea, but decreased body weight which were reversed by Azadirachta indica extract and sulfasalazine (positive control) treatments. Azadirachta indica extract showed antibacterial activity. Azadirachta indica extract and sulfasalazine enhanced the antioxidants but decreased free radicals and myeloperoxidase activities affected in trinitrobenzene sulfonic acid-induced colitis. Azadirachta indica extract, thus seemed to be effective in healing trinitrobenzene sulfonic acid-induced colitis in rats.

  8. Secondary current properties generated by wind-induced water waves in experimental conditions

    Directory of Open Access Journals (Sweden)

    Michio Sanjou

    2014-06-01

    Full Text Available Secondary currents such as the Langmuir circulation are of high interest in natural rivers and the ocean because they have striking impacts on scour, sedimentation, and mass transport. Basic characteristics have been well-studied in straight open-channel flows. However, little is known regarding secondary circulation induced by wind waves. The presented study describes the generation properties of wind waves observed in the laboratory tank. Wind-induced water waves are known to produce large scale circulations. The phenomenon is observed together with high-speed and low-speed streaks, convergence and divergence zones, respectively. Therefore, it is important to determine the hydrodynamic properties of secondary currents for wind-induced water waves within rivers and lakes. In this study, using two high-speed CMOS cameras, stereoscopic particle image velocimetry (PIV measurements were conducted in order to reveal the distribution of all three components of velocity vectors. The experiments allowed us to investigate the three-dimensional turbulent structure under water waves and the generation mechanism of large-scale circulations. Additionally, a third CMOS camera was used to measure the spanwise profile of thefree-surface elevation. The time-series of velocity components and the free-surface were obtained simultaneously. From our experiments, free-surface variations were found to influence the instantaneous velocity distributions of the cross-sectional plane. We also considered thegeneration process by the phase analysis related to gravity waves and compared the contribution of the apparent stress.

  9. Effects of calcium antagonists on K(+)-induced contraction in isolated aorta from diabetic and age-matched control rats

    NARCIS (Netherlands)

    Heijnis, J. B.; van Zwieten, P. A.

    1993-01-01

    The effects of nifedipine, verapamil and diltiazem on K(+)-induced contraction were investigated in isolated aortic rings from diabetic and age-matched control rats. Six weeks after streptozotocin injection there was no significant difference between the maximum isometric contraction to KCl (80

  10. Hepatoprotective effect of engineered silver nanoparticles coated bioactive compounds against diethylnitrosamine induced hepatocarcinogenesis in experimental mice.

    Science.gov (United States)

    Prasannaraj, Govindaraj; Venkatachalam, Perumal

    2017-02-01

    Nanoparticle based drug delivery can rapidly improves the therapeutic potential of anti-cancer agents. The present study focused to evaluate the hepatoprotective activity of silver nanoparticles (AgNPs) synthesized using aqueous extracts of Andrographis paniculata leaves (ApAgNPs) and Semecarpus anacardium nuts (SaAgNPs) against diethylnitrosamine (DEN) induced liver cancer in mice model. The physico-chemical properties of synthesized AgNPs were characterized by Fourier transform infrared (FTIR) spectroscopy, Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED), X-ray Diffraction (XRD), Energy Dispersive X-ray (EDX) spectrum, Zeta potential and Dynamic Light Scattering (DLS) analysis. The surface plasmon resonance (SPR) absorption spectrum revealed a strong peak at 420nm for both SaAgNPs and ApAgNPs. FTIR results exhibited the presence of possible functional groups in the synthesized AgNPs. TEM analysis determined the hexagonal, and spherical shape of the synthesized silver nanoparticles. The XRD and SAED pattern confirmed the crystalline nature and crystalline size of the AgNPs. EDX result clearly showed strong silver signals in the range between 2 and 4keV. Zeta potential measurements indicated a sharp peak at -3.93 and -13.8mV for ApAgNPs and SaAgNPs, respectively. DLS measurement expressed the particle size distribution was 70 and 60nm for ApAgNPs and SaAgNPs, respectively. DEN (20mg/kg b.wt.) was subjected to induce liver cancer in mice for 8weeks and treated with biosynthesized silver nanoparticles. Interestingly, ApAgNPs and SaAgNPs treated DEN induced animal groups show a decreased level of aspartate amino transferase (AST), alanine amino transferase (ALT), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) activity and elevated level of catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and superoxide dismutase (SOD) activity over untreated DEN control

  11. Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.

    Science.gov (United States)

    Deshmukh, Rahul; Kaundal, Madhu; Bansal, Vikas; Samardeep

    2016-07-01

    Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (plearning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. 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.

  13. 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.

  14. Experimental and numerical characterization of wind-induced pressure coefficients on nuclear buildings and chimney exhausts

    Energy Technology Data Exchange (ETDEWEB)

    Ricciardi, Laurent, E-mail: laurent.ricciardi@irsn.fr; Gélain, Thomas; Soares, Sandrine

    2015-10-15

    Highlights: • Experiments on scale models of nuclear buildings and chimney exhausts were performed. • Pressure coefficient fields on buildings are shown for various wind directions. • Evolution of pressure coefficient vs U/W ratio is given for various chimney exhausts. • RANS simulations using SST k–ω turbulence model were performed on most studied cases. • A good agreement is overall observed, with Root Mean Square Deviation lower than 0.15. - Abstract: Wind creates pressure effects on different surfaces of buildings according to their exposure to the wind, in particular at external communications. In nuclear facilities, these effects can change contamination transfers inside the building and can even lead to contamination release into the environment, especially in damaged (ventilation stopped) or accidental situations. The diversity of geometries of facilities requires the use of a validated code for predicting pressure coefficients, which characterize the wind effect on the building walls and the interaction between the wind and chimney exhaust. The first aim of a research program launched by the French Institut de Radioprotection et de Sûreté Nucléaire (IRSN), was therefore to acquire experimental data of the mean pressure coefficients for different geometries of buildings and chimneys through wind tunnel tests and then to validate a CFD code (ANSYS CFX) from these experimental results. The simulations were performed using a steady RANS approach and a two-equation SST k–ω turbulence model. After a mesh sensitivity study for one configuration of building and chimney, a comparison was carried out between the numerical and experimental values for other studied configurations. This comparison was generally satisfactory, averaged over all measurement points, with values of Root Mean Square Deviations lower than 0.15 for most cases.

  15. Minimal Physiologically Based Pharmacokinetic and Drug-Drug-Disease Interaction Model of Rivaroxaban and Verapamil in Healthy and Renally Impaired Subjects.

    Science.gov (United States)

    Ismail, Mohamed; Lee, Vincent H; Chow, Christina R; Rubino, Christopher M

    2017-12-14

    Current dosing recommendations for rivaroxaban advocate dosage reduction in patients with moderate to severe renal impairment and avoidance of concomitant strong inhibitors of CYP3A or P-glycoprotein. However, rivaroxaban dosing in patients with mild renal impairment taking concomitant moderate inhibitors of CYP3A and P-glycoprotein is not addressed. To quantify the impacts of concomitant verapamil administration and renal impairment on rivaroxaban pharmacokinetics, a minimal physiologically based pharmacokinetic model system was developed and used to evaluate potential increases in rivaroxaban exposure and the consequent increase in risk of major bleeding. Data from a phase 1, drug-drug interaction study were used to qualify the minimal physiologically based pharmacokinetic model system. Model-based simulations indicate that coadministration of rivaroxaban with verapamil substantially increases rivaroxaban exposure across all renal function categories, resulting in an exponential increase in bleeding risk. Reduction of the daily rivaroxaban dose to 10 to 15 mg reduces the major bleeding risk below the designated 4.5% threshold in the majority of patients with normal or mildly impaired renal function. A reduction to 10 mg daily in patients with moderate to severe renal impairment provides additional risk reduction so that 90% of those patients fall below the 4.5% threshold. A risk threshold of 4.5% was selected because it is the median predicted risk in patients treated concomitantly with ketoconazole, which is contraindicated for use with rivaroxaban. Patients taking both rivaroxaban and verapamil should take a reduced daily dose of rivaroxaban to minimize bleeding risk. © 2017, The American College of Clinical Pharmacology.

  16. Experimental Study of Synchro-Betatron Coupling Induced By Dipole Modulation

    Energy Technology Data Exchange (ETDEWEB)

    Syphers, M.; Ball, M.; Brabson, B.; Budnick, J.; Caussyn, D.D.; Chao, A.W.; Collins, J.; Derenchuk, V.; Dutt, S.; East, G.; Ellison, M.; Ellison, T.; Friesel, D.; Gabella, W.; Hamilton, B.; Huang, H.; Jones, W.P.; Lee, S.Y.; Li, D.; Minty, M.G.; Nagaitsev, S.; /Unlisted /Indiana U., IUCF /SLAC /Fermilab /Argonne /Brookhaven

    2011-11-04

    Synchro-betatron coupling in a proton storage ring with electron cooling was studied experimentally by modulating a transverse dipole field close to the synchrotron frequency. The combination of the electron cooling and transverse field modulation on the synchrotron oscillation is equivalent to a dissipative parametric resonant system. The proton bunch was observed to split longitudinally into two pieces, or beamlets, converging toward attractors of the dissipative system. These phenomena might be important in understanding the effect of ground vibration on the Superconducting Super Collider beam, and the effect of power supply ripple on the Relativistic Heavy-Ion Collider beam.

  17. Experimental and clinical studies with radiofrequency-induced thermal endometrial ablation for functional menorrhagia

    Energy Technology Data Exchange (ETDEWEB)

    Phipps, J.H.; Lewis, B.V.; Prior, M.V.; Roberts, T. (Watford General Hospital, Herts (England))

    1990-11-01

    A method of ablating the endometrium has been introduced into clinical practice that uses radiofrequency electromagnetic energy to heat the endometrium, using a probe inserted through the cervix. Preliminary studies suggest that over 80% of patients treated will develop either amenorrhea or a significant reduction in flow. The advantages of radiofrequency endometrial ablation over laser ablation or resection are the avoidance of intravascular fluid absorption, simplicity (no special operative hysteroscopic skills are required), speed of operation, and reduced cost compared with the Nd:YAG laser. In this paper, we describe the experimental studies performed during development of this new technique.

  18. Experimental analysis of energy harvesting from self-induced flutter of a composite beam

    Energy Technology Data Exchange (ETDEWEB)

    Zakaria, Mohamed Y., E-mail: zakaria@vt.edu; Al-Haik, Mohammad Y.; Hajj, Muhammad R. [Virginia Tech, Norris Hall, Blacksburg, Virginia 24061 (United States)

    2015-07-13

    Previous attempts to harvest energy from aeroelastic vibrations have been based on attaching a beam to a moving wing or structure. Here, we exploit self-excited oscillations of a fluttering composite beam to harvest energy using piezoelectric transduction. Details of the beam properties and experimental setup are presented. The effects of preset angle of attack, wind speed, and load resistance on the levels of harvested power are determined. The results point to a complex relation between the aerodynamic loading and its impact on the static deflection and amplitudes of the limit cycle oscillations on one hand and the load resistance and level of power harvested on the other hand.

  19. Protective effect of Calotropis procera latex extracts on experimentally induced gastric ulcers in rat.

    Science.gov (United States)

    Bharti, S; Wahane, V D; Kumar, V L

    2010-02-03

    Calotropis procera is a wild growing plant with multifarious medicinal properties. The present study was carried out to evaluate the effect of dried latex (DL) of Calotropis procera and its methanol extract (MeDL) against gastric ulcers induced in rats. Aqueous suspension of DL (20 and 100mg/kg) and MeDL (10 and 50mg/kg) were given orally to 36h fasted rats and ulcers were induced by ethanol, pyloric ligation and aspirin. Parameters like ulcer score and levels of oxidative stress markers were measured in all the models. The effect on gastric hemorrhage and tissue histology was studied in ethanol model and on acidity, pH and volume of gastric secretion was evaluated in pyloric ligation model. The protective effect of DL and MeDL was compared with that of standard anti-ulcer drug famotidine (20 mg/kg). DL and MeDL produced 85-95% inhibition of gastric mucosal damage in ethanol model and 70-80% inhibition in aspirin model. The protective effect of these extracts was associated with marked reduction in gastric hemorrhage, maintenance of tissue integrity and normalization of levels of oxidative stress markers like glutathione, thiobarbituric acid reactive substances and superoxide dismutase. Like famotidine, DL and MeDL decreased the gastric acidity from 376.17+/-21.47 mequiv./l to 163.88+/-6.86 and 201.48+/-8.86 mequiv./l respectively in pyloric ligation model. These extracts increased the gastric pH without affording any protection to gastric mucosa in this model. The latex of Calotropis procera has the therapeutic potential to relieve gastric hyperacidity and to prevent gastric ulceration induced by necrotizing agents. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  20. Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia.

    Science.gov (United States)

    Constantinescu, Ioana M; Bolfa, Pompei; Constantinescu, Dan; Mironiuc, Aurel I; Gherman, Claudia D

    2017-01-01

    Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.

  1. Effect of Oxysterol-Induced Apoptosis of Vascular Smooth Muscle Cells on Experimental Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Sonia Perales

    2009-01-01

    Full Text Available Smooth muscle cells (SMCs undergo changes related to proliferation and apoptosis in the physiological remodeling of vessels and in diseases such as atherosclerosis and restenosis. Recent studies also have demonstrated the vascular cell proliferation and programmed cell death contribute to changes in vascular architecture in normal development and in disease. The present study was designed to investigate the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, using an in vivo/in vitro cell model in which SMCs were isolated and culture from chicken exposed to an atherogenic cholesterol-rich diet (SMC-Ch and/or an antiatherogenic fish oil-rich diet (SMC-Ch-FO. Cells were exposed in vitro to 25-hydroxycholesterol to study levels of apoptosis and apoptotic proteins Bcl-2, Bcl-XL and Bax and the expression of bcl-2 and bcl-xL, genes. The quantitative real-time reverse transcriptase-polymerase chain reaction and the Immunoblotting western blot analysis showed that 25-hydroxycholesterol produces apoptosis in SMCs, mediated by a high increase in Bax protein and Bax gene expression. These changes were more marked in SMC-Ch than in SMC-Ch-FO, indicating that dietary cholesterol produces changes in SMCs that make them more susceptible to 25-hydroxycholesterol-mediated apoptosis. Our results suggest that the replacement of a cholesterol-rich diet with a fish oil-rich diet produces some reversal of cholesterol-induced changes in the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, making SMCs more resistant to apoptosis.

  2. [Therapeutic efficacy of Bushengzhuyang Fang (Yangjing Capsule) on phytoestrogen-induced erectile dysfunction: an experimental study].

    Science.gov (United States)

    Zhou, Yu-Chun; Li, Tian-Fu; Sun, Zhi-Xing; Fan, Qian; Liu, Tao; Jin, Bao-Fang

    2014-12-01

    To investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats. Fifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH). At 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

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

    DEFF Research Database (Denmark)

    Oji, Satoru; Nicolussi, Eva-Maria; Kaufmann, Nathalie

    2016-01-01

    , 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....

  4. Wound healing activity of Carica papaya L. in experimentally induced diabetic rats.

    Science.gov (United States)

    Nayak, Shivananda B; Pinto Pereira, Lexley; Maharaj, Dale

    2007-08-01

    The aqueous extract of C. papaya fruit (100 mg kg(-1) day(-1) for 10 days) was evaluated for its wound healing activity in streptozotocin-induced diabetic rats using excision and dead space wound models. Extract-treated animals exhibited 77% reduction in the wound area when compared to controls which was 59%. The extract treated wounds were found to epithelize faster as compared to controls. The wet and dry granulation tissue weight and hydroxyproline content increased significantly when compared to controls. The extract exhibited antimicrobial activity against the five organisms tested. Carica papaya promotes significant wound healing in diabetic rats and further evaluation of this activity in humans is suggested.

  5. Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

    Science.gov (United States)

    Qu, Chang; Yuan, Zhong-Wen; Yu, Xiu-Ting; Huang, Yan-Feng; Yang, Guang-Hua; Chen, Jian-Nan; Lai, Xiao-Ping; Su, Zi-Ren; Zeng, Hui-Fang; Xie, Ying; Zhang, Xiao-Jun

    2017-07-01

    Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to

  6. An experimental study of hemolysis induced by onion (Allium cepa) poisoning in dogs.

    Science.gov (United States)

    Tang, X; Xia, Z; Yu, J

    2008-04-01

    The mechanism of hemolysis induced by onion poisoning in dogs was studied. Six adult, clinically normal Pekingese dogs were fed cooked onions at 30 g/kg body weight/day for 2 days. Blood samples were collected on days 1, 3, 5, 8, 12, 18 and 24 after onion administration, and urine was collected the day after bleeding. Red blood cell counts, hemoglobin and hematocrit were decreased from day 1, and significantly so on day 5 (P onion poisoning in dogs causes hemolytic anemia.

  7. Experimental observation of disorder induced self-focusing in optical fibers

    Energy Technology Data Exchange (ETDEWEB)

    Leonetti, Marco, E-mail: marco.leonetti@roma1.infn.it [Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena, 291 00161 Roma (Italy); Karbasi, Salman [Department of Electrical and Computer Engineering, University of California, San Diego, La Jolla, California 92093 (United States); Mafi, Arash [Department of Physics and Astronomy and Center for High Technology Materials, University of New Mexico, Albuquerque, New Mexico 87131 (United States); Conti, Claudio [ISC-CNR and Department of Physics, University Sapienza, P.le Aldo Moro 5, I-00185, Roma (Italy)

    2014-10-27

    We observed disorder induced focusing nonlinearity activated by a monochromatic light beam in optical fibers composed by two kinds of plastics. The two materials, arranged in disordered fashion, support modes with a degree of localization which increases with the intensity of the optical beam. The temporal response of the optical fiber demonstrates the thermal origin of this nonlinearity. Measurements of the localization length as a function of the input power with broadband and monochromatic inputs show the effectiveness of focusing action with respect to the case of homogeneous fibers.

  8. Experimental approach to measure thick target neutron yields induced by heavy ions for shielding

    Directory of Open Access Journals (Sweden)

    Trinh N.D.

    2017-01-01

    Full Text Available Double differential (angular and energy neutron distributions were measured using an activation foil technique. Reactions were induced by impinging two low-energy heavy-ion beams accelerated with the GANIL CSS1 cyclotron: (36S (12 MeV/u and 208Pb (6.25 MeV/u onto thick natCu targets. Results have been compared to Monte-Carlo calculations from two codes (PHITS and FLUKA for the purpose of benchmarking radiation protection and shielding requirements. This comparison suggests a disagreement between calculations and experiment, particularly for high-energy neutrons.

  9. Can exit prizes induce lame ducks to shirk less? Experimental evidence

    Directory of Open Access Journals (Sweden)

    Leif Helland

    2012-12-01

    Full Text Available Elected representatives serving their final period face only weak incentives to provide costly effort. However, overlapping generations (OLG models suggest that exit prizes sustained by trigger strategies can induce representatives in their final period to provide such effort. We evaluate this hypothesis using a simple OLG public good experiment, the central treatment being whether exit prizes are permitted. We find that a significantly higher number of subjects in their final period contribute when exit prizes are permitted. However, this result does not originate from use of trigger strategies. More likely explanations include gift-exchange and focal-point effects.

  10. Experimental investigation and theoretical calculation for 3He induced nuclear reactions on vanadium

    Science.gov (United States)

    Ali, B. M.; Al-Abyad, M.; Seddik, U.; El-Kameesy, S. U.; Ditrói, F.; Takács, S.; Tárkányi, F.

    2016-04-01

    Using stacked-foil activation technique and gamma-ray spectrometry, excitation functions for 3He induced nuclear reactions on natV were measured. Cross-sections for natV(3He, xn)52m,gMn and natV(3He, pxn)51Cr nuclear reactions were measured up to 27 MeV utilizing the MGC-20E cyclotron of ATOMKI. The measurements establish for the first time consistent excitation curves. Comparisons with results for values derived from different theoretical codes were included. Integral yield were calculated.

  11. Experimental excitation functions of deuteron induced reactions on natural thallium up to 50 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Adam Rebeles, R., E-mail: radamreb@vub.ac.be [Cyclotron Laboratory, Vrije Universiteit Brussel, B-1090 Brussels (Belgium); Van den Winkel, P.; Hermanne, A. [Cyclotron Laboratory, Vrije Universiteit Brussel, B-1090 Brussels (Belgium); Tarkanyi, F.; Takacs, S. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen H-4026 (Hungary)

    2012-10-01

    Excitation functions of deuteron induced reactions on natural thallium leading to the formation of {sup 204m,203m2+m1+g,202m,201m+g,200}Pb and {sup 202,201m+g,200m+g}Tl isotopes were determined up to 50 MeV. The cross sections were measured by an activation technique using stacked foil irradiation. The excitation functions of the investigated reactions are compared with data reported in literature and also with the theoretical results of TALYS nuclear reaction code. From the measured cross section data, the thick target yield for the medical interesting {sup 203}Pb isotope is calculated.

  12. Experimental investigation and theoretical calculation for {sup 3}He induced nuclear reactions on vanadium

    Energy Technology Data Exchange (ETDEWEB)

    Ali, B.M. [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); Al-Abyad, M., E-mail: alabyad_m@yahoo.com [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); Seddik, U. [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); El-Kameesy, S.U. [Physics Department, Faculty of Science, Ain Shams University, Cairo (Egypt); Ditrói, F.; Takács, S.; Tárkányi, F. [Institute for Nuclear Research (ATOMKI), Hungarian Academy of Sciences, Debrecen H4026 (Hungary)

    2016-04-15

    Using stacked-foil activation technique and gamma-ray spectrometry, excitation functions for {sup 3}He induced nuclear reactions on {sup nat}V were measured. Cross-sections for {sup nat}V({sup 3}He, xn){sup 52m,g}Mn and {sup nat}V({sup 3}He, pxn){sup 51}Cr nuclear reactions were measured up to 27 MeV utilizing the MGC-20E cyclotron of ATOMKI. The measurements establish for the first time consistent excitation curves. Comparisons with results for values derived from different theoretical codes were included. Integral yield were calculated.

  13. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

    Directory of Open Access Journals (Sweden)

    Georgios Liappas

    2015-01-01

    Full Text Available Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

  14. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

    Science.gov (United States)

    Liappas, Georgios; Gónzalez-Mateo, Guadalupe Tirma; Majano, Pedro; Sánchez- Tomero, José Antonio; Ruiz-Ortega, Marta; Martín, Pilar; Sanchez-Díaz, Raquel; Selgas, Rafael; López-Cabrera, Manuel; Aguilera Peralta, Abelardo

    2015-01-01

    Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. PMID:26064907

  15. Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness.

    Science.gov (United States)

    Drake, C L; Roehrs, T A; Royer, H; Koshorek, G; Turner, R B; Roth, T

    There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Parallel control group comparison. Sleep laboratory in a large urban medical center. Twenty-one men and women with susceptibility to the rhinovirus type 23. Nasal inoculation with rhinovirus type 23. Polysomnographically recorded sleep for five nights (2300-0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3-5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.

  16. Blood gas stability and hematological changes in experimentally-induced acute porcine pleuropneumonia.

    Science.gov (United States)

    Kiorpes, A L; Mirsky, M L; MacWilliams, P S; Bäckström, L R; Collins, M T

    1989-01-01

    Blood gas and hematological responses to acute, mild Actinobacillus pleuropneumoniae infection of growing pigs was studied. Six pigs (average weight 10.1 kg) were experimentally infected intranasally with A. pleuropneumoniae serotype 5. Four pigs served as controls. Rectal temperatures and arterial blood for gas analysis and hematology were taken at 0, 8, 16, 24, 48 and 72 h postinfection. All infected pigs became febrile showing clinical signs typical of mild to moderate porcine pleuropneumonia; controls remained asymptomatic. Neutrophilia with bands and lymphopenia were observed only in infected pigs. Arterial partial pressures of O2 and CO2, and pH did not change in infected pigs. All pigs were killed after 72 h, and lungs were examined and cultured. Gross and microscopic lesions consistent with porcine pleuropneumonia were seen in 3/6 and 5/6 infected lungs, respectively. Control lungs were grossly normal with no histological evidence of pleuropneumonia. We conclude that in mild, acute porcine pleuropneumonia as established experimentally, a leukogram typical of acute inflammation and stress is seen; however, hypoxemia and alveolar hypoventilation are not features of this form of the disease. PMID:2914231

  17. Desferal-Induced Inhibition of Lipid Peroxidation Processes in Experimental Pancreatic Necrosis

    Directory of Open Access Journals (Sweden)

    Yu. P. Orlov

    2007-01-01

    Full Text Available Objective: To experimentally reduce the activity of hyperoxidative processes in experimental pancreatic necrosis, by pread-ministering desferal as a Fe2+ chelator, and to determine the implication of ionized iron in the intensification of endotoxi-cosis, one of the leading risk factors of multiple organ dysfunctions.Subjects and methods. An experiment was carried out in 60 albino male rats in which pancreatic necrosis was simulated, by administering 0.25 ml of autobile per kg into the pancreas and by ligating the common bile duct just at the mouth of the duodenum. The parameters of endogenous intoxication (the levels of oligopeptides and the rate of free radical oxidation processes were estimated in the experiment. The impact of prophylactic desferal administration on the parameters was also evaluated.Results. It has been ascertained that pread-ministration (3 hours before the simulation of pancreatic necrosis of desferal in a dose of 80 mg/kg can prevent the potentiation of LPO processes, which substantially reduces endotoxicosis that develops in pancreatic necrosis.Conclusion. The findings give grounds to use desferal in clinical practice as a pathogenetically warranted agent to perform an abolishing therapy for one of the pathogenetic factors (oxidative stress in acute progressive pancreatitis. 

  18. Sensory Re-Weighting in Human Bipedal Postural Control: The Effects of Experimentally-Induced Plantar Pain.

    Directory of Open Access Journals (Sweden)

    Antoine Pradels

    Full Text Available The present study was designed to assess the effects of experimentally-induced plantar pain on the displacement of centre of foot pressure during unperturbed upright stance in different sensory conditions of availability and/or reliability of visual input and somatosensory input from the vestibular system and neck. To achieve this goal, fourteen young healthy adults were asked to stand as still as possible in three sensory conditions: (1 No-vision, (2 Vision, and (3 No-vision - Head tilted backward, during two experimental conditions: (1 a No-pain condition, and (2 a condition when a painful stimulation was applied to the plantar surfaces of both feet (Plantar-pain condition. Centre of foot pressure (CoP displacements were recorded using a force platform. Results showed that (1 experimentally-induced plantar pain increased CoP displacements in the absence of vision (No-vision condition, (2 this deleterious effect was more accentuated when somatosensory information from the vestibular and neck was altered (No-vision - Head tilted backward condition and (3 this deleterious effect was suppressed when visual information was available (Vision condition. From a fundamental point of view, these results lend support to the sensory re-weighting hypothesis whereby the central nervous system dynamically and selectively adjusts the relative contributions of sensory inputs (i.e. the sensory weightings in order to maintain balance when one or more sensory channels are altered by the task (novel or challenging, environmental or individual conditions. From a clinical point of view, the present findings further suggest that prevention and treatment of plantar pain may be relevant for the preservation or improvement of balance control, particularly in situations (or individuals in which information provided by the visual, neck proprioceptive and vestibular systems is unavailable or disrupted.

  19. Efficacy of extended pirlimycin therapy for treatment of experimentally induced Streptococcus uberis intramammary infections in lactating dairy cattle.

    Science.gov (United States)

    Oliver, Stephen P; Almeida, Raul A; Gillespie, Barbara E; Ivey, Susan J; Moorehead, Hugh; Lunn, Phillip; Dowlen, Henry H; Johnson, David L; Lamar, Ken C

    2003-01-01

    Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, around the time of calving, and during early lactation. Strategies for controlling S. uberis mastitis have not received adequate research attention and are therefore poorly defined