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Sample records for calcium antagonistic effects

  1. Magnesium: Effect on ocular health as a calcium channel antagonist

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    Şafak Korkmaz

    2013-06-01

    Full Text Available Magnesium is the physiologic calcium channel blocker,involving in many different metabolic processes by maintainingcell membrane function, modulating smooth musclecontraction and influencing enzymatic activities. Magnesiumhas been shown to increase blood flow to tissuesby modifying endothelial function via endothelin-1 (ET-1and nitric Oxide (NO pathways. Magnesium also exhibitsneuroprotective role by blocking N-methyl-D-aspartate(NMDA receptor related calcium influx and by inhibitingthe release of glutamate, hence protects the cell againstoxidative stress and apoptosis. Both increase in bloodflow and its neuroprotective effect make magnesium agood candidate for glaucoma studies. Magnesium hasbeen shown to decrease oxidative stress and apoptosisin retinal tissue and to have retinal ganglion cell sparingeffect. A series of studies has been conducted aboutmagnesium could decrease insulin resistance in diabeticpatients, ease glycemia control and prevent diabetic retinopathy.Magnesium is found to be critically important inmaintaining normal ionic homeostasis of lens. Magnesiumdeficiency has been shown to cause increased lenticularoxidative stress and ionic imbalance in the lens so triggercataractogenesis. J Clin Exp Invest 2013; 4 (2: 244-251Key words: Magnesium, calcium channel blockage,glaucoma, neuroprotection, diabetic retinopathy, cataract

  2. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  3. PROTECTIVE EFFECTS OF CALCIUM ANTAGONIST ON VASCULAR SYSTEM AGAINST TOXICITY INDUCED BY MERCURIC CHLORIDE

    Institute of Scientific and Technical Information of China (English)

    马欣; 厉英倩; 白宇飞; 刘明

    2004-01-01

    Objective To explore the toxic effects of mercuric chloride (HgCl2) on vascular smooth muscle as well as its relationship to calcium antagonist. Methods By using isolated vascular tension methods, we studied the effect of HgCl2 on isolated rabbit aortic rings. Results HgCl2 (1-100μmol*L-1) caused a concentration-dependent contraction of rabbit aortic rings, which did not change with phentolamin or without endothelium. In KH solution with Ca2+ , the maximum contraction amplitude reduced by(61.2±3.3)%. Nifedipine produced a concentration-dependent decrease of the maximum contraction amplitude. Conclusion Calcium antagonist has protective effects on vascular smooth muscle against damage induced by HgCl2.

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

    NARCIS (Netherlands)

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

    1988-01-01

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

  5. Differences between negative inotropic and vasodilator effects of calcium antagonists acting on extra- and intracellular calcium movements in rat and guinea-pig cardiac preparations

    NARCIS (Netherlands)

    Hugtenburg, J.G.; Mathy, M.-J.; Boddeke, H.W.G.M.; Beckeringh, J.J.; Van Zwieten, P.A.

    1989-01-01

    In order to get more insight into the utilization of calcium in the mammalian heart and the influence of calcium antagonists on this process we have evaluated the negative inotropic and vasodilator effect of nifedipine, diltiazem, verapamil, bepridil and lidoflazine as well as of the intracellularly

  6. [Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion].

    Science.gov (United States)

    Manna, V

    1991-11-01

    Treatment with lithium salts produces improvements in bipolar affective disorders. Up to date, the relationship between neurochemical and behavioural effects of lithium and its actions on intraneuronal free calcium ions is not well known. Some calcium antagonist drugs resulted active in the treatment of bipolar affective syndromes, with therapeutic effects similar to lithium salts. Some studies suggest that also lithium salts act as calcium antagonist at intraneuronal level. In this preliminary open study the activity of nimodipine, a selective neuronal calcium antagonist drug, was evaluated alone and in association with lithium salts in the treatment of rapid cycling bipolar manic-depressive illness. During three periods of 6 months 12 rapid cycling patients were treated with lithium salts, lithium salts plus nimodipine 30 mg x 3/day, nimodipine 30 mg x 3/day. The association of lithium with nimodipine resulted more effective than lithium alone or nimodipine alone in the reduction of episodes of affective disorder. These results suggest a probable sinergic activity of both treatments. Further studies will be necessary to confirm the mechanism of action, perhaps calcium antagonism, at the basis of therapeutic effects of both treatments. The results seem to confirm the hypothesis that a calcium-ionic disorders play a role in the pathogenesis of bipolar affective disorders.

  7. Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice.

    Science.gov (United States)

    Serrano, A; Menéndez, J; Casarejos, M J; Solano, R M; Gallego, E; Sánchez, M; Mena, M A; García de Yebenes, J

    2005-08-01

    Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls. PK-KO mice have high striatal dopamine levels and increased dopamine metabolism in spite of low reduced tyrosine hydroxylase protein. Cinnarizine, which blocks dopamine receptors and increases dopamine release, further increased dopamine metabolism. PK-KO mice increased GSH levels as a compensatory mechanism against enhanced free radical production related to acceleration of dopamine turnover. Neuronal markers, such as beta-tubulin slightly increased in PK-KO and furthermore with cinnarizine. Astroglial markers were decreased in PK-KO mice, and this effect was potentiated by cinnarizine, suggesting abnormal glia in these animals. Microglia was hyperactivated in PK-KO midbrain, suggesting inflammation in these animals. Proapoptotic proteins were increased by cinnarizine and, to a lesser extent, in PK-KO mice. Our data indicate that mutation of parkin is a risk factor for drug-induced parkinsonism. PMID:15993444

  8. Calcium antagonistic effects of Bambusa Rigida investigated by 45Ca and its protection on myocardial ischemia of rats

    Institute of Scientific and Technical Information of China (English)

    LIN Rushan; YE Ling; YANG Yuanyou; LIAO Jiali; MO Shangwu; LIU Ning

    2008-01-01

    An investigation was conducted using 45Ca as a radioactive tracer to evaluate calcium antagonistic effects of several extracts from Bambusa Rigida in living rats. The relationship between the flavonoid and saccharide contents of Bambusa Rigida and calcium antagonistic effects were also analyzed. The protective effects of the alkali extracts ofBambusa Rigida on myocardial ischemia were investigated in living rats. The results indicated that the alkali extracts of Bambusa Rigida had a prominent influence on Ca2+ influx and efflux in the isolated rat aorta and heart, as they could obviously block 45Ca entering into cells and stimulate efflux of intracellular Ca2+. Moreover, the alkali extracts of Bambusa Rigida had favorable protective effects on myocardial ischemia induced either by isoproterenol injection (ISO) or by the ligation of coronary artery. These results implied that the Bambusa Rigida had attractive potential for the treatment of heart, cerebrovascular and other diseases. However, the conclusion that whether the flavonoid or saccharide in Bambusa Rigida affected the calcium antagonistic effects and Ca2+ channels or not was hard to make within the results of the investigation.

  9. "Synthesis and smooth muscle Calcium channel antagonist effects of new derivatives of 1,4-Dihydropyridine containing Nitroimidazol substituent "

    Directory of Open Access Journals (Sweden)

    Miri R

    2002-09-01

    Full Text Available A group of racemic 3-[(2-hydroxyethyl, (2-Methoxyethyl, (2-acetylethyl or (2-cyanoethyl], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle (GPILSM which was induced by carbacol (1.67 χ 10^-7 M. All compounds exhibited calcium channel antagonist activity (IC50=10^-12 to 10^-13 M range comparable to nifedipine as reference drug (IC50=1.07±0.12x 10^-11 M.

  10. Secondary prevention with calcium antagonists after acute myocardial infarction

    DEFF Research Database (Denmark)

    Hansen, J F

    1992-01-01

    Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival...

  11. Effects of isradipine and other calcium antagonists on arteriovenous-shunt flow in anesthetized rabbits and cats

    Energy Technology Data Exchange (ETDEWEB)

    Hof, R.P.

    1989-04-17

    The effects of vasodilators on arteriovenous (AV)-shunt flow was investigated in anesthetized cats and rabbits, using the tracer microsphere method. In cats, the calcium antagonist isradipine reduced AV-shunt flow; verapamil showed a similar tendency and nicardipine was without effect. Dihydralazine strongly increased, but nitroglycerin and dipyridamole decreased AV-shunt flow. In rabbits, the effects of isradipine and verapamil were similar to those seen in cats. Sodium nitroprusside had no effect, whereas prazosin, minoxidil, and the potassium-channel activator cromakalim increased AV-shunt flow. The contrasting effects of drugs sharing the same mechanism of action suggest that target-tissue selectivity is more important than the mechanism of action. An increase of AV-shunt flow is unlikely to be beneficial but could be associated with a number of undesirable side effects. It might negatively affect migraine sufferers and, if AV-shunt dilatation shows no tolerance development, it represents an unnecessary hemodynamic burden for the heart.

  12. "Synthesis and smooth muscle Calcium channel antagonist effect of Alkyl, Aminoalkyl 1,4-Dihydro-2,6-Dimethyl-4-Nitroimidazole-3,5 Pyridine Dicarboxylates "

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    Miri R

    2001-08-01

    Full Text Available The discovery that 1,4-dihydropyridine (DHP class of calcium channel antagonist inhibits the Ca+² influx represented a major therapeutic advance in the treatment of cardiovascular diseases such as hypertension, angina pectoris and other spastic smooth muscle disorders. A novel class of calcium channel antagonist of flunarizine containing arylpiperazinyl moiety has recently been reported. It was therefore of interest to determine the effect that selected C-3 substituents contained amino alkyl and arylpiperazine, in conjunction with a C-4 1-methyl-5-nitro-2-imidazolyl substituents on calcium channel antagonist activity. The unsymmetrical analogues were prepared by a procedure reported by Meyer in which 1-methyl-5-nitro-imidazol-2-carboxaldehyde was reacted with acetoacetic esters and alkyl 3-aminocrotonate. In vitro calcium channel antagonist activities were determined by the use of high K+ contraction of guinea pig ileal longitudinal smooth muscle. All compounds exhibited comparable calcium channel antagonist activity (IC50=10^-9 to 10^-11 M against reference drug nifedipine (IC50=2.75±0.36 x 10^-10 M.

  13. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

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    Bruce Lyeth

    2013-06-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.

  14. Radioprotective effect of calcium channel antagonist nifedipine on rat lungs following thoracic X-ray irradiation

    International Nuclear Information System (INIS)

    Nifedipine was administered to rats following 18 Gy thoracic irradiation. Compared with the rats subjected to irradiation alone, in rats administered nifedipine after irradiation, although there was no difference in the phospholipid contents in lung lavage fluid and in the number of type 2 pneumocytes, the survival rate within 30 days and body weight increased, lung weight decreased, in lung lavage fluid the macrophages increased and the neutrophils decreased in number, and pathological changes in lung abated. These results indicated that nifedipine had marked radioprotective effect on rat lungs following thoracic X-ray irradiation. The possible mechanism of the effect is discussed

  15. Renal hemodynamics in hypertensive renal allograft recipients: effects of calcium antagonists and ACE inhibitors.

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    Grekas, D; Dioudis, C; Kalevrosoglou, I; Alivanis, P; Derveniotis, V; Tourkantonis, A

    1996-06-01

    Hypertension present in more than 50% of successfully renal transplanted patients and its prevalence has slightly increased since the introduction of cyclosporine A. Twenty patients, 9 women and 11 men aged from 30 to 58 years, with stable cadaveric renal allograft function and moderate to severe hypertension, were included in the study. Renal artery graft stenosis causing hypertension were excluded. All patients were given triple drug immunosuppressive treatment with methylprednisolone, azathioprine and cyclosporine A (CsA) and their hypertension was treated with a nifedipine dose of 20 mg twice daily. To evaluate the effect of ACE inhibitors on renal hemodynamics and hypertension, a 4 mg/daily dose of perindopril was added to the above regimen for two months. Effective renal plasma flow (ERPF) decreased from 208 +/- 54 to 168 +/- 61 ml/min and renal vascular resistance (RVR) increased from 75 +/- 12 to 88 +/- 17 mm Hg/ml/min (P nifedipine. It is suggested that the combination of both antihypertensive agents was more effective than monotherapy with nifedipine in controlling blood pressure, but less favorable on the renal hemodynamic response in hypertensive renal transplant patients who were maintained on CsA.

  16. The effect of the calcium antagonist, isradipine, on working capacity, pulmonary function, morbidity and survival rate in patients with severe chronic obstructive pulmonary disease (COPD): a randomized, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Galløe, Anders Michael; Graudal, Niels Albert; Petersen, J.R.;

    1991-01-01

    Beneficial effects of calcium antagonists on the pulmonary haemodynamics of patients with chronic obstructive pulmonary disease (COPD) have been observed in several studies. Such effects include a decrease in pulmonary vascular resistance, an increase in cardiac output, and an increase in oxygen ...... to these parameters. It is concluded that the existing evidence does not justify the introduction of calcium antagonists as part of the routine treatment of COPD....

  17. Pharmacokinetic interactions with calcium channel antagonists (Part I).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-11-01

    Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. PMID:1773549

  18. Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

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    Farzin Hadizadeh

    2010-01-01

    Full Text Available Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT1 and L-type calcium channels were investigated on isolated rat aorta. Materials and MethodsAortic rings were pre-contracted with 1 µM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution.ResultsThe results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100,000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. ConclusionFinally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents.

  19. Pharmacokinetic interactions with calcium channel antagonists (Part II).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-12-01

    Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents. PMID:1782739

  20. Effects of glycoprotein Ⅱb/Ⅲa antagonists and chloride channel blockers on platelet cytoplasmic free calcium

    Institute of Scientific and Technical Information of China (English)

    YIN Song-mei; XIE Shuang-feng; NIE Da-nian; LI Yi-qing; LI Hai-ming; MA Li-ping; WANG Xiu-ju; WU Yu-dan; FENG Jian-hong

    2005-01-01

    @@ Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱb/Ⅲa (GP Ⅱb/Ⅲa) is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GPⅡb/Ⅲa is the process of thrombosis. Ca2+ is an important intracellular second messenger in platelet activation. It has been reported that GPⅡb/Ⅲa receptors were involved in the calcium influx of activated platelet, and GPⅡb/Ⅲa receptor had characteristics of calcium channel or an adjacent calcium channel.

  1. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

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    S. Y. Martsevich

    2015-12-01

    Full Text Available The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antagonists is stressed.

  2. The acute effects of intravenously administered mibefradil, a new calcium antagonist, on the electrophysiologic characteristics of the human heart

    NARCIS (Netherlands)

    Rosenquist, M; BrembillaPerrot, B; Meinertz, T; Neugebauer, A; Crijns, HJMG; Smeets, JLRM; vanderVring, JAFM; Fromer, M; Kobrin, [No Value

    1997-01-01

    Objective: This multicenter, double-blind, placebo-controlled, parallel-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human heart. Methods: Seventy-one patients referred for routine electrophysiologic testing were rand

  3. Synthesis of carbon-11 labelled calcium channel antagonists

    International Nuclear Information System (INIS)

    A useful synthetic approach to carbon-11 labelled 1,4-dihydropyridines is described. Carbon-11 labelled calcium channel antagonists 11C-Nifedipine, 11C-Nisoldipine, 11C-nitrendipine and 11C-CF3-Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with 11CH3I produced the labelled compounds in very good chemical and radiochemical yields (94%). (author)

  4. Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists.

    Science.gov (United States)

    King, G N; Fullinfaw, R; Higgins, T J; Walker, R G; Francis, D M; Wiesenfeld, D

    1993-04-01

    Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Effect of calcium antagonists and metabolic inhibitors on the retention of adriamycin, in both free and liposomal form, in a number of tumor cells lines

    International Nuclear Information System (INIS)

    Adriamycin (ADR) encapsulated in liposomes (MLV-ADR) accumulated at a lower rate, with a concomitant reduced cytotoxicity, in comparison to the free drug form (F-ADR) in all murine tumors tested. However, inhibition of [3H] thymidine incorporation into DNA appeared nearly equal between F-ADR and MLV-ADR treated tumor cells suggesting that the concentration necessary to inhibit DNA synthesis is only a fraction of the total drug content within the cells. Electrophoretic mobility of tumor cells was unaffected by exposure to either F-ADR or MLV-ADR. The metabolic inhibitor N-ethylmaleimide (NEM) when coincubated with F-ADR in P388 adriamycin-resistant leukemia cells (P388-ADR) resulted in a marked increase in intracellular drug accumulation. Use of the calcium channel blockers verapamil (VRP) and N-3,4-dimethoxyphenethyl)-N-methyl-2-(2-napthyl)-m-dithane-2-propylamine hydrochloride, (DMDP), a derivative of verapamil, in conjunction with adriamycin treatment demonstrated a near reversal of resistance in P388/ADR. Retention of drug increased 4-5 fold in the presence of each of the calcium antagonists in vitro studies with a concomitant drop in viability which surpassed that observed in P388/O. P388/ADR tumor bearing mice treated with the combination of VRP or DMDP and F-ADR exhibited no increase in mean survival times (MST) over F-ADR therapy alone. Scanning electron microscopy (SEM) studies of P388/O tumor cells demonstrated numerous, small villi-like processes, whereas P388/ADR cells possessed many large membraneous folds. Transmission electron microscopy (TEM) demonstrated not only the membrane folding seem by SEM, but also the presence of large numbers of C type viral particles in P388/ADR cells in comparison to the small amounts detected in P388/O cells

  6. Different effects of calcium antagonist and beta-blocker therapy on left-ventricular diastolic function in ischemic heart disease. A direct comparison of the impact of mibefradil and atenolol

    DEFF Research Database (Denmark)

    Hassager, C; Thygesen, K; Grande, P;

    2001-01-01

    OBJECTIVE: To compare the effect of a calcium antagonist and a beta-blocker on left-ventricular diastolic function in patients with ischemic heart disease. METHODS: 138 patients with chronic stable angina pectoris were randomized in a multicenter, double-blind trial to treatment with either...... mibefradil or atenolol for 6 weeks (50 mg once daily for 2 weeks followed by 100 mg once daily for 4 weeks). The ratio between early (E) and late (A) diastolic mitral flow velocities (E/A), the E wave deceleration time (DT) and the left ventricular isovolumetric relaxation time (IRT) were measured by Doppler...... echocardiography as parameters of left-ventricular diastolic function initially, after 4 and after 6 weeks of treatment. RESULTS: Mibefradil did not change the E/A ratio significantly (+4%, NS), while atenolol treatment resulted in a significant increase in the E/A ratio (+20%, p treatment...

  7. Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine.

    Science.gov (United States)

    Martínez, J A; Bello, A; Rubio, L L; Rodríguez, C; Galán, L; Caudales, E; Alvarez, J L

    1998-01-01

    The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro-5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for cycleanine and nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The results suggest that cycleanine can act as a potent vascular selective Ca-antagonist. PMID:9565772

  8. Effects of N- and L-type calcium channel antagonists on the responses of nociceptive spinal cord neurons to mechanical stimulation of the normal and the inflamed knee joint.

    Science.gov (United States)

    Neugebauer, V; Vanegas, H; Nebe, J; Rümenapp, P; Schaible, H G

    1996-12-01

    innocuous and noxious pressure applied to the noninflamed ankle joint. 3. The topical administration of nimodipine decreased the responses to innocuous and noxious pressure applied to the knee in a sample of 9 neurons with input from the normal joint and in a sample of 16 neurons with input from the inflamed knee joint (hyperexcitable neurons). Within administration times of 30 min, the responses were reduced to approximately 70% of the predrug values. In hyperexcitable neurons, the responses to innocuous and noxious pressure applied to the knee were also decreased during ionophoretic administration of nimodipine (6 neurons) and diltiazem (9 neurons). When the noninflamed ankle was stimulated, the responses to innocuous pressure were reduced neither in neurons with input from the normal knee nor in neurons with input from the inflamed knee, but the responses of hyperexcitable neurons to noxious pressure onto the ankle were reduced. The ionophoretic administration of the agonist at the L-type calcium channel, S(-)-Bay K 8644, enhanced the responses to mechanical stimulation of the knee joint in all 14 hyperexcitable neurons tested. The effect of S(-)-Bay K 8644 was counteracted by both diltiazem (in 6 of 6 neurons) and nimodipine (in 5 of 5 neurons). 4. These data show that antagonists at both the N- and the L-type voltage-dependent calcium channels influence the spinal processing of input from the knee joint. The data suggest, therefore, that voltage-dependent calcium calcium channels of both the N and the L type are important for the sensory functions of the spinal cord. They are involved in the spinal processing of nonnociceptive as well as nociceptive mechanosensory input from the joint, both under normal and inflammatory conditions. The present results show in particular that N- and L-type channels are likely to be involved in the generation of pain evoked by noxious mechanical stimulation in normal tissue as well as in the mechanical hyperalgesia that is usually pres

  9. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

    Science.gov (United States)

    Graudins, Andis; Lee, Hwee Min; Druda, Dino

    2016-03-01

    Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock. PMID:26344579

  10. AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels

    International Nuclear Information System (INIS)

    In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) [3H]ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) [3H]nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing

  11. Effective use of TNF antagonists

    OpenAIRE

    Yocum, David

    2004-01-01

    Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined...

  12. Antischistosomal activity of a calcium channel antagonist on schistosomula and adult Schistosoma mansoni worms

    Directory of Open Access Journals (Sweden)

    Vanessa Silva-Moraes

    2013-08-01

    Full Text Available Current schistosomiasis control strategies are largely based on chemotherapeutic agents and a limited number of drugs are available today. Praziquantel (PZQ is the only drug currently used in schistosomiasis control programs. Unfortunately, this drug shows poor efficacy in patients during the earliest infection phases. The effects of PZQ appear to operate on the voltage-operated Ca2+channels, which are located on the external Schistosoma mansoni membrane. Because some Ca2+channels have dihydropyridine drug class (a class that includes nifedipine sensitivity, an in vitro analysis using a calcium channel antagonist (clinically used for cardiovascular hypertension was performed to determine the antischistosomal effects of nifedipine on schistosomula and adult worm cultures. Nifedipine demonstrated antischistosomal activity against schistosomula and significantly reduced viability at all of the concentrations used alone or in combination with PZQ. In contrast, PZQ did not show significant efficacy when used alone. Adult worms were also affected by nifedipine after a 24 h incubation and exhibited impaired motility, several lesions on the tegument and intense contractility. These data support the idea of Ca2+channels subunits as drug targets and favour alternative therapeutic schemes when drug resistance has been reported. In this paper, strong arguments encouraging drug research are presented, with a focus on exploring schistosomal Ca2+channels.

  13. [Cutaneous adverse effects of TNFalpha antagonists].

    Science.gov (United States)

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  14. The T-type calcium channel antagonist Z944 disrupts prepulse inhibition in both epileptic and non-epileptic rats.

    Science.gov (United States)

    Marks, Wendie N; Greba, Quentin; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2016-09-22

    The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure of sensorimotor gating which is a basic process whereby the brain filters incoming stimuli to enable appropriate responding in sensory rich environments. The regulation of PPI involves a network of limbic, cortical, striatal, pallidal and pontine brain areas, many of which show high levels of T-type calcium channel expression. Therefore, we tested the effects of blocking T-type calcium channels on PPI with the potent and selective T-type antagonist Z944 (0.3, 1, 3, 10mg/kg; i.p.) in adult Wistar rats and two related strains, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non-Epileptic Control (NEC). PPI was tested using a protocol that varied prepulse intensity (3, 6, and 12dB above background) and prepulse-pulse interval (30, 50, 80, 140ms). Z944 decreased startle in the Wistar strain at the highest dose relative to lower doses. Z944 dose-dependently disrupted PPI in the Wistar and GAERS strains with the most potent effect observed with the higher doses. These findings suggest that T-type calcium channels contribute to normal patterns of brain activity that regulate PPI. Given that PPI is disrupted in psychiatric disorders, future experiments that test the specific brain regions involved in the regulation of PPI by T-type calcium channels may help inform therapeutic development for those suffering from sensorimotor gating impairments. PMID:27365170

  15. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  16. Effect of calmodulin antagonists on the growth and graviresponsiveness of primary roots of maize

    Science.gov (United States)

    Stinemetz, C. L.; Hasenstein, K. H.; Young, L. M.; Evans, M. L.

    1992-01-01

    We examined the effect of calmodulin (CaM) antagonists applied at the root tip on root growth, gravity-induced root curvature, and the movement of calcium across the root tip and auxin (IAA) across the elongation zone of gravistimulated roots. All of the CaM antagonists used in these studies delayed gravity-induced curvature at a concentration (1 micromole) that did not affect root growth. Calmodulin antagonists (> or = 1 micromole) inhibited downward transport of label from 45Ca2+ across the caps of gravistimulated roots relative to the downward transport of 45Ca2+ in gravistimulated roots which were not treated with CaM antagonists. Application of CaM antagonists at the root tip (> or = 1 micromole) also decreased the relative downward movement of label from 3H-IAA applied to the upper side of the elongation zone of gravistimulated roots. In general, tip application of antagonists inhibited neither the upward transport of 45Ca2+ in the root tip nor the upward movement of label from 3H-IAA in the elongation zone of gravistimulated roots. Thus, roots treated with CaM antagonists > or = 1 micromole become less graviresponsive and exhibit reduced or even a reversal of downward polarity of calcium transport across the root tip and IAA transport across the elongation zone. The results indicate that calmodulin-regulated events play a role in root gravitropism.

  17. SNX-325, a novel calcium antagonist from the spider Segestria florentina.

    Science.gov (United States)

    Newcomb, R; Palma, A; Fox, J; Gaur, S; Lau, K; Chung, D; Cong, R; Bell, J R; Horne, B; Nadasdi, L

    1995-07-01

    A novel selective calcium channel antagonist peptide, SNX-325, has been isolated from the venom of the spider Segestria florentina. The peptide was isolated using as bioassays the displacement of radioiodinated omega-conopeptide SNX-230 (MVIIC) from rat brain synaptosomal membranes, as well as the inhibition of the barium current through cloned expressed calcium channels in oocytes. The primary sequence of SNX-325 is GSCIESGKSCTHSRSMKNGLCCPKSRCNCRQIQHRHDYLGKRKYSCRCS, which is a novel amino acid sequence. Solid-phase synthesis resulted in a peptide that is chromatographically identical with the native peptide and which has the same configuration of cysteine residues as the spider venom peptide omega-Aga-IVa [Mintz, I. M., et al., (1992) Nature 355, 827-829]. At micromolar concentrations, SNX-325 is an inhibitor of most calcium, but not sodium or potassium, currents. At nanomolar concentrations, SNX-325 is a selective blocker of the cloned expressed class B (N-type), but not class C (cardiac L), A, or E, calcium channels. SNX-325 is approximately equipotent with the N-channel selective omega-conopeptides (GVIA and MVIIA as well as closely related synthetic derivatives) in blocking the potassium induced release of tritiated norepinephrine from hippocampal slices (IC50s, 0.1-0.5 nM) and in blocking the barium current through cloned expressed N-channels in oocytes (IC50s 3-30 nM). By contrast, SNX-325 is 4-5 orders of magnitude less potent than is SNX-111 (synthetic MVIIA) at displacing radioiodinated SNX-111 from rat brain synaptosomal membranes. SNX-325 will be a useful comparative tool in further defining the function and pharmacology of the N- and possibly other types of high-voltage activated calcium channels. PMID:7541240

  18. ACE inhibitors and calcium antagonists in the treatment of congestive heart failure

    DEFF Research Database (Denmark)

    Hansen, J F

    1995-01-01

    The increased mortality after myocardial infarction is related to the risk of reinfarction, sudden death, and the development and progression of heart failure; in congestive heart failure it is due to the progression of heart failure and sudden death. ACE inhibitors have been proven to prevent...... cardiovascular events, especially the progression of heart failure, in postinfarct patients with reduced ejection fraction and heart failure in the SAVE and AIRE trials. In patients with congestive heart failure, ACE inhibitor treatment has prevented cardiovascular death and reduced morbidity due to progressive...... heart failure in the SOLVD trials. In post-myocardial infarction patients, the calcium antagonist nifedipine did not affect mortality or morbidity; diltiazem improved prognosis in patients without congestive heart failure and in patients with non-Q-wave infarction; and verapamil improved prognosis...

  19. Phosphorylation and calcium antagonistically tune myosin-binding protein C's structure and function.

    Science.gov (United States)

    Previs, Michael J; Mun, Ji Young; Michalek, Arthur J; Previs, Samantha Beck; Gulick, James; Robbins, Jeffrey; Warshaw, David M; Craig, Roger

    2016-03-22

    During each heartbeat, cardiac contractility results from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filaments to shorten cellular length. Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filament that appears to tune these mechanochemical interactions by its N-terminal domains transiently interacting with actin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding velocity. Both functional mechanisms are potentially further tunable by phosphorylation of an intrinsically disordered, extensible region of cMyBP-C's N terminus, the M-domain. Using atomic force spectroscopy, electron microscopy, and mutant protein expression, we demonstrate that phosphorylation reduced the M-domain's extensibility and shifted the conformation of the N-terminal domain from an extended structure to a compact configuration. In combination with motility assay data, these structural effects of M-domain phosphorylation suggest a mechanism for diminishing the functional potency of individual cMyBP-C molecules. Interestingly, we found that calcium levels necessary to maximally activate the thin filament mitigated the structural effects of phosphorylation by increasing M-domain extensibility and shifting the phosphorylated N-terminal fragments back to the extended state, as if unphosphorylated. Functionally, the addition of calcium to the motility assays ablated the impact of phosphorylation on maximal sliding velocities, fully restoring cMyBP-C's inhibitory capacity. We conclude that M-domain phosphorylation may have its greatest effect on tuning cMyBP-C's calcium-sensitization of thin filaments at the low calcium levels between contractions. Importantly, calcium levels at the peak of contraction would allow cMyBP-C to remain a potent contractile modulator, regardless of cMyBP-C's phosphorylation state.

  20. Effect of BN 52021, a specific antagonist of platelet activating factor (PAF-acether), on calcium movements and phosphatidic acid production induced by PAF-acether in human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.F.; Chap, H.; Braquet, P.; Douste-Blazy, L.

    1987-02-15

    /sup 32/P-labelled human platelets loaded with quin 2 and pretreated with aspirin were stimulated with 1-100 nM platelet activating factor (PAF-acether or 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in a medium containing the ADP-scavenging system creatine phosphate/creatine phosphokinase. Under these conditions, PAF-acether evoked a characteristic fluorescence change allowing to quantify elevations in cytoplasmic free Ca/sup 2 +/ from internal stores (Ca/sup 2 +/ mobilization) or from external medium (Ca/sup 2 +/ influx), as well as an increased production of phosphatidic acid, reflecting phospholipase C activation. These effects, which can be attributed to PAF-acether only and not to released products such as ADP or thromboxane A2, were strongly inhibited in a dose-dependent manner by BN 52021, a specific antagonist of PAF-acether isolated from Ginkgo biloba. As the drug remained inactive against the same effects elicited by thrombin, it is concluded that BN 52021 does not interfere directly with the mechanism of transmembrane signalling involving inositol-phospholipids or (and) some putative receptor-operated channels, but rather acts on the binding of PAF-acether to its presumed membrane receptor.

  1. Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

    DEFF Research Database (Denmark)

    Haunsø, Stig; Sejrsen, Per; Svendsen, Jesper Hastrup

    1991-01-01

    of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion......Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion....... In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion...

  2. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit+ bosentan group and Nit+ losartan group. Nitroglycerin tolerance was induced by 2-day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg- 1· d- 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg- 1· d- 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit+ losartan group and Nit+ bosentan group compared with Nit group [(31.95± 4.45 ) % vs (21.00± 3.69 ) % , P Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance .

  3. Penta-substituted benzimidazoles as potent antagonists of the calcium-sensing receptor (CaSR-antagonists).

    Science.gov (United States)

    Gerspacher, Marc; Altmann, Eva; Beerli, René; Buhl, Thomas; Endres, Ralf; Gamse, Rainer; Kameni-Tcheudji, Jacques; Kneissel, Michaela; Krawinkler, Karl Heinz; Missbach, Martin; Schmidt, Alfred; Seuwen, Klaus; Weiler, Sven; Widler, Leo

    2010-09-01

    A series of novel benzimidazole derivatives has been designed via a scaffold morphing approach based on known calcilytics chemotypes. Subsequent lead optimisation led to the discovery of penta-substituted benzimidazoles that exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR) inhibitory profiles. In addition, synthesis and structure-activity relationship data are provided.

  4. Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

    Science.gov (United States)

    Gulizia, M; Valenti, R; Platania, F; D'Onofrio, V; Rizzini, P; Circo, A

    1994-01-01

    Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose). PMID:7609494

  5. Action of pinaverium bromide, a calcium-antagonist, on gastrointestinal motility disorders.

    Science.gov (United States)

    Christen, M O

    1990-01-01

    1. The evidence reviewed here indicates that pinaverium bromide (Dicetel) relaxes gastrointestinal (GI) structures primarily by inhibiting Ca2+ influx through potential-dependent channels of surface membranes of smooth muscle cells. 2. The in vivo selectivity of pinaverium bromide for the GI tract appears to be due mainly to its pharmacokinetic properties. Because of its low absorption (typical for quaternary ammonium compounds) and marked hepatobiliary excretion, most of the orally-administered dose of pinaverium bromide remains in the GI tract. 3. Orally-administered pinaverium bromide does not elicit adverse cardiovascular side-effects at doses that effectively relieve GI spasm, pain, transit disturbances and other symptoms related to motility disorders. 4. Pinaverium bromide is the only Ca2(+)-antagonist with known therapeutic efficacy in the treatment of irritable bowel syndrome and certain other functional intestinal disorders. PMID:2177709

  6. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    张建梅; 陈永红; 王晓红; 唐朝枢

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n =6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment ofnitroglycerin patch (0. 05mg/h). Angiotensin I1 receptor antagonist losartan (10mg ·kg-1·d-1) and endothe-lin receptor antagonist bosentan ( 100 mg·kg-1· d-1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effec-tive percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentangroup compared with Nit group [(31.95±4.45) % vs (21.00±3.69) %, P <0.01and (33. 18±6. 16)% vs (21.00±3.69 ) %, P < 0. 01 , respectivelyl. The maximal vessel relaxation induced by SNP was thesame in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response toSNP) was found in tolerant group[ (34 ±10) nmol/L, P < 0. 01 ]. The ET-1 amounts in plasma and vasculartissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P<0. 01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartangroup compared with those in Nit group ( P < 0.01 ). Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance.

  7. Behavioural effects of histamine and its antagonists: a review.

    Science.gov (United States)

    White, J M; Rumbold, G R

    1988-01-01

    This review focuses on the behavioural effects of histamine and drugs which affect histaminergic function, particularly the H1- and H2-receptors antagonists. Research in this area has assumed considerable importance with increasing interest in the role of brain histamine, the clinical use of both H1 and H2 antagonists and evidence of nonmedical use of H1 antagonists. Results from a number of studies show that H1 and H2 antagonists have clear, but distinct subjective effects and that H1 antagonists have discriminative effects in animals. While H1 antagonists are reinforcers in certain conditions, histamine itself is a punisher. Moderate doses of H1 antagonists affect psychomotor performance in some situations, but the results are variable. The exceptions are terfenadine and astemizole, which do not seem to penetrate the blood-brain barrier readily. In studies of schedule-controlled behaviour, marked changes in response rate have been observed following administration of H1 antagonists, with the magnitude and direction dependent on the dose and the baseline behaviour. Histamine reduces avoidance responding, an effect mediated via H1-receptors. Changes in drinking and aggressive behaviour have also been observed following histamine administration and distinct roles for H1- and H2-receptors have been delineated. Separate H1- and H2-receptor mechanisms have also been suggested to account for changes in activity level. While the H2 antagonists do not always have strong behavioural effects when administered peripherally, there is evidence that cimetidine has a depressant effect on sexual function. These and other findings reveal an important role for histaminergic systems in a wide range of behaviour. PMID:3133686

  8. 钙通道阻滞剂对胃泌素促人结肠癌细胞增殖的影响%Effects of Calcium Channel Antagonist on Gastrin-induced Pro liferation of HT29 Colon Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    吴浩; 张正; 黄兴兰; 魏于全; 雷松

    2001-01-01

    Objective This study aimed to assess the effects of nifedipine ongastrin-induced proliferation of HT29 colon carcinoma cells and inqurire into the possible mech anisms. Methods Flow cytometry was used to monitor the cytoplas mic free calcium; MTT colorimetry was used to determine the proliferation of HT2 9 cells.Results The results showed that 2.5×10-6 mol/L pentagastrin(PG) induced a quick rise of intracellular free calcium(〔Ca2+ 〕i)(P<0.01). 10-5 mol/L nifedipin e can significantly inhibited the rise of 〔Ca2+〕i induced by pentagas tri n(P<0.01), in parallel, at growth assay we demonstrated that 10-5-10-6mol/L nifedipine could obviously block the increase in cell number elicit ed by 2.5×10-6 mol/L PG. Conculsion These data indicate that nifedipine can stop the influx of Ca2+ and hence inhibit the pentaga strin-induced proliferation.%目的 观察硝苯地平(Nif)对五肽胃泌素促人结肠癌细胞增殖的影响并初步探讨其作用机制。方法 采用流式细胞仪检测细胞内游离钙离子浓度水平(〔Ca2+〕i),结合MTT比色法测定细胞增殖情况。结果 2.5×10-6mol/L的五肽胃泌素(PG)作用于HT29细胞后,可引起〔Ca2+〕i水平迅速升高(P<0.01)。10-5mol/L的Nif可使PG引起的〔Ca2+〕i水平升高幅度明显降低(P<0.01),同时10-5~10-6mol/L的Nif可以抑制PG促HT29细胞增殖的作用(P<0.05)。结论 Nif通过抑制胞外Ca2+内流,阻止〔Ca2+〕i水平升高,是其抑制PG促HT29细胞增殖的一个主要机制。

  9. 钙拮抗剂在高血压治疗中的应用%Application of calcium antagonists in hypertension

    Institute of Scientific and Technical Information of China (English)

    徐胜勇

    2012-01-01

    Calcium antagonists have become the first - line drug in the treatment of hypertension, and the use of which has been keeping in clinical first position since 2000 in China. Besides its definite efficacy in lowering blood pressure, calcium antagonists can remarkably protect the functions of many important organs such as brain, heart and kidney. It is widely used in hypertension of the elderly, isolated systolic hypertension and hypertension with angina, peripheral vessels, carotid atherosclerosis, diabetes or pregnancy with few side - effects and no absolute contraindication.%钙拮抗剂从21世纪初已成为高血压的第一线用药,2000年以来在国内临床高血压药用量上一直占据第一.钙拮抗剂除了有明确的降压作用外,还具有显著的保护心、脑、肾等脏器功能的作用,对于老年性高血压、收缩期高血压、合并心绞痛、外周血管病、颈动脉粥样硬化、糖尿病、妊娠都是强适应证,副作用小,无绝对使用禁忌证.

  10. Structure-activity studies on 1,4-dihydropyridine calcium channel antagonists and activators

    International Nuclear Information System (INIS)

    Four series of 1,4-dihydropyridine Ca2+ channel antagonists related to mifedipine were synthesized by a modified Hantzsch procedure to determine the effects of ester (C3 = CO2Me, C5 = CO2R) and phenyl (C4) substituents on pharmacological and radioligand binding ([H]nitrendipine) activities in guinea pig ileal longitudinal smooth muscle. Two series of Ca2+ channel activator 1,4-dihydropyridines, BAY K 8644 (C3 = NO2, C5 = CO2Me) and CGP 28392 (C2,3 = lactone, C5 = CO2Me) were biochemically evaluated by inhibition of [3H]nitrendipine binding in guinea pig ileal longitudinal smooth muscle membranes to establish fundamental structure-activity requirements. A homologous series of bis-1,4-dihydropyridines were synthesized, pharmacologically and biochemically evaluated in an attempt to explore the distribution of the 1,4-dihydropyridine receptor in guinea pig ileal longitudinal smooth muscle membranes. Several potential affinity labels including ester substituted 3- and 4-fluorosulfonyl benzoyl and isothiocyanate derivatives were synthesized and evaluated by inhibition of [3H]nitrendipine binding

  11. Determinants of effective, safe and convenient vitamin K antagonist use

    NARCIS (Netherlands)

    Kooistra, Hilde Afra Margaretha

    2016-01-01

    Vitamin K antagonists (VKA) are frequently used anticoagulants. They are very effective in preventing atrial fibrillation related strokes and recurrent venous thrombosis. However, it can be difficult to achieve an optimal balance between the efficacy and side effects (bleeding), as the dose response

  12. The use of [11C]diazomethane for labelling a calcium channel antagonist: PN 200-110 (Isrodipine)

    International Nuclear Information System (INIS)

    PN 200-110 (Isrodipine), a calcium channel antagonist, was labelled with 11C (t1/2 20.4 min) by a reaction between [11C]diazomethane and the carboxyl precursor. The [11C]CH2N2 is prepared in two stages from [11C]CH4: [11C]CH4→[11C]CHCl3→[11C]CH2N2. When a mixture of nitrogen (95%) and hydrogen (5%) is irradiated with 20 MeV protons (30 min, 30 μ A), 60-80 mCi of product are prepared and purified with HPLC. The 11C product is ready for medical use within 35 min of the end of bombardment. (author)

  13. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    Science.gov (United States)

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  14. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  15. [Control of generalized chronic periodontitis combined with calcium-antagonist-related gingival overgrowth by a complex periodontal-endodontic-prosthodontic treatment. Case report].

    Science.gov (United States)

    Szánto, Erika; Gera, István

    2011-12-01

    To day a relatively high percentage of elderly population of the industrialized world suffers with different cardiovascular diseases and are on permanent antihypertensive therapy. One of the most frequently used drugs is the calcium channel blockers prescribed against high blood pressure. The most common oral side effect of these drugs is the gingival enlargement that might develop even on otherwise healthy gingiva. The incidence of chronic periodontitis in this age group is also high and the Ca antagonist medication in those individuals might substantially modify the clinical course of periodontal inflammation leading to gingival enlargement and hypertrophic pocket wall. The case presented here is a 52 years old hypertonic woman with a long history of Ca-antagonist therapy and generalized chronic periodontitis combined with gingival hyperplasia. After the change of medication the 1,5 years comprehensive periodontal endodontic and prosthodontic therapy restored patient's periodontal health and provided complex dental rehabilitation. Nevertheless, only regular periodontal supportive therapy could ensure predictable outcome and guarantee long lasting periodontal health.

  16. Solution structure of the calcium channel antagonist omega-conotoxin GVIA.

    OpenAIRE

    Skalicky, J. J.; Metzler, W. J.; Ciesla, D. J.; Galdes, A.; Pardi, A

    1993-01-01

    The three-dimensional solution structure is reported for omega-conotoxin GVIA, which is a potent inhibitor of presynaptic calcium channels in vertebrate neuromuscular junctions. Structures were generated by a hybrid distance geometry and restrained molecular dynamics approach using interproton distance, torsion angle, and hydrogen-bonding constraints derived from 1H NMR data. Conformations of GVIA with low constraint violations converged to a common peptide fold. The secondary structure in th...

  17. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  18. Effects of Nickel on Calcium Phosphate Formation

    Science.gov (United States)

    Guerra-López, J.; González, R.; Gómez, A.; Pomés, R.; Punte, G.; Della Védova, C. O.

    2000-05-01

    We have investigated the effect of nickel on calcium phosphate formation from aqueous solutions. The calcium phosphates prepared under different reaction conditions (pH, temperature, and nickel concentration) were characterized by X-ray diffraction, FTIR spectroscopy, and chemical analysis. The apatite compounds were also studied thermogravimetrically. From the combined results of the techniques employed we have determined that nickel favors the formation of brushite and amorphous calcium phosphate. We have found, as well, that the presence of nickel in the solution inhibits calcium hydroxyapatite (CaHAP) and octacalcium phosphate formation. However in the synthesis performed at basic pH and 95°C the apatitic phase (HAP) could be obtained. The present results suggest that the presence of nickel may modify the precipitation of oral calcium phosphate.

  19. Biological effects of growth hormone and its antagonist.

    Science.gov (United States)

    Okada, S; Kopchick, J J

    2001-03-01

    Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and has been implicated in diabetic eye and kidney damage. Additionally the GH/IGF-1 system has been postulated as a risk factor for several types of cancers. Thus both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago the first drug of a new class, a GH antagonist, was discovered. This molecule is now being tested for its ability to combat the effects of high circulating levels of GH. Here, we discuss some of the detrimental actions of GH, and how a GH antagonist can be used to combat these effects. PMID:11286784

  20. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists

    International Nuclear Information System (INIS)

    The biological activity of the (+)-S- and (-)-R-enantiomers of niguldipine, of the (-)-S- and (+)-R-enantiomers of felodipine and nitrendipine, and of rac-nisoldipine and rac-nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)-mimetic U-46619 in guinea pig Langendorff hearts, displacement of (+)-[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T-tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross-contamination was less than 0.5% for both S- and R-enantiomers of niguldipine and nitrendipine and less than 1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)-(S)-/(-)-(R)-niguldipine, (-)-(S)-/(+)-(R)-felodipine, and (-)-(S)-/(+)-(R)-nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio rac-nisoldipine/rac-nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)-(S)-/(-)-(R)-niguldipine = 45 and 35, (-)-(S)-/(+)-(R)-felodipine = 12 and 13, (-)-(S)-/(+)-(R)-nitrendipine = 8 and 8, and rac-nisoldipine/rac-nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U-46619-induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity

  1. Studies of the voltage-sensitive calcium channels in smooth muscle, neuronal, and cardiac tissues using 1,4-dihydropyridine calcium channel antagonists and activators

    International Nuclear Information System (INIS)

    This study describes the investigation of the voltage-sensitive Ca+ channels in vascular and intestinal smooth muscle, chick neural retina cells and neonatal rat cardiac myocytes using 1,4-dihydropyridine Ca2+ channel antagonists and activators. In rat aorta, the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) produced Ca2+-dependent contractile responses. The responses to TPA were blocked by the Ca2+ channel antagonists. The effects of the enantiomers of Bay K 8644 and 202-791 were characterized in both rat tail artery and guinea pig ileal longitudinal smooth muscle preparations using pharmacologic and radioligand binding assays. The (S)-enantiomers induced contraction and potentiated the responses to K+ depolarization. The (R)-enantiomers inhibited the tension responses to K+. All the enantiomers inhibited specific [3H]nitrendipine binding. The pharmacologic activities of both activator and antagonist ligands correlated on a 1:1 basis with the binding affinities. In chick neural retina cells the (S)-enantiomers of Bay K 8644 and 202-791 enhanced Ca2+ influx. In contrast, the (R)-enantiomers inhibited Ca2+ influx. The enantiomers of Bay K 8644 and 202-791 inhibited specific [3H]PN 200-110 binding competitively. Binding of 1,4-dihydropyridines was characterized in neonatal rat heart cells

  2. Antagonistic Regulation of Parvalbumin Expression and Mitochondrial Calcium Handling Capacity in Renal Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Henzi

    Full Text Available Parvalbumin (PV is a cytosolic Ca2+-binding protein acting as a slow-onset Ca2+ buffer modulating the shape of Ca2+ transients in fast-twitch muscles and a subpopulation of neurons. PV is also expressed in non-excitable cells including distal convoluted tubule (DCT cells of the kidney, where it might act as an intracellular Ca2+ shuttle facilitating transcellular Ca2+ resorption. In excitable cells, upregulation of mitochondria in "PV-ergic" cells in PV-/- mice appears to be a general hallmark, evidenced in fast-twitch muscles and cerebellar Purkinje cells. Using Gene Chip Arrays and qRT-PCR, we identified differentially expressed genes in the DCT of PV-/- mice. With a focus on genes implicated in mitochondrial Ca2+ transport and membrane potential, uncoupling protein 2 (Ucp2, mitocalcin (Efhd1, mitochondrial calcium uptake 1 (Micu1, mitochondrial calcium uniporter (Mcu, mitochondrial calcium uniporter regulator 1 (Mcur1, cytochrome c oxidase subunit 1 (COX1, and ATP synthase subunit β (Atp5b were found to be up-upregulated. At the protein level, COX1 was increased by 31 ± 7%, while ATP-synthase subunit β was unchanged. This suggested that these mitochondria were better suited to uphold the electrochemical potential across the mitochondrial membrane, necessary for mitochondrial Ca2+ uptake. Ectopic expression of PV in PV-negative Madin-Darby canine kidney (MDCK cells decreased COX1 and concomitantly mitochondrial volume, while ATP synthase subunit β levels remained unaffected. Suppression of PV by shRNA in PV-expressing MDCK cells led subsequently to an increase in COX1 expression. The collapsing of the mitochondrial membrane potential by the uncoupler CCCP occurred at lower concentrations in PV-expressing MDCK cells than in control cells. In support, a reduction of the relative mitochondrial mass was observed in PV-expressing MDCK cells. Deregulation of the cytoplasmic Ca2+ buffer PV in kidney cells was counterbalanced in vivo and in vitro

  3. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    Science.gov (United States)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  4. The effect of calcium gluconate and other calcium supplements as a dietary calcium source on magnesium absorption in rats.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Yasui, H; Watanuki, M

    1997-01-01

    The effects of commercially available calcium supplements (calcium carbonate, calcium gluconate, oyster shell preparation and bovine bone preparation) and gluconic acid on the absorption of calcium and magnesium were evaluated for 30 days in male Wistar rats. There were no differences in the apparent absorption ratio of calcium among rats fed each calcium supplement; however, the rats fed the calcium gluconate diet had a higher apparent absorption ratio of magnesium than the rats fed the other calcium supplements. Dietary gluconic acid also more markedly stimulated magnesium absorption than the calcium carbonate diet, and the bone (femur and tibia) magnesium contents of rats fed the gluconic acid diet were significantly higher than those of the rats fed the calcium carbonate diet. Furthermore, the weight of cecal tissue and the concentrations of acetic acid and butyric acid in cecal digesta of rats fed the calcium gluconate diet or the gluconic acid diet were significantly increased. We speculate that the stimulation of magnesium absorption in rats fed the calcium gluconate diet is a result of the gluconic acid component and the effect of gluconic acid on magnesium absorption probably results from cecal hypertrophy, magnesium solubility in the large intestine and the effects of volatile fatty acids on magnesium absorption.

  5. Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro

    International Nuclear Information System (INIS)

    The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that varapamil (104-105M) and nimodipine (104-106M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by stimultancous addition of calcium chloride (5x103M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blokade of specific voltage-dependent calcium channels. (author)

  6. Huwentoxin-XVI, an analgesic, highly reversible mammalian N-type calcium channel antagonist from Chinese tarantula Ornithoctonus huwena.

    Science.gov (United States)

    Deng, Meichun; Luo, Xuan; Xiao, Yucheng; Sun, Zhenghua; Jiang, Liping; Liu, Zhonghua; Zeng, Xiongzhi; Chen, Hanchun; Tang, Jianhua; Zeng, Weimin; Songping Liang

    2014-04-01

    N-type calcium channels play important roles in the control of neurotransmission release and transmission of pain signals to the central nervous system. Their selective inhibitors are believed to be potential drugs for treating chronic pain. In this study, a novel neurotoxin named Huwentoxin-XVI (HWTX-XVI) specific for N-type calcium channels was purified and characterized from the venom of Chinese tarantula Ornithoctonus huwena. HWTX-XVI is composed of 39 amino acid residues including six cysteines that constitute three disulfide bridges. HWTX-XVI could almost completely block the twitch response of rat vas deferens to low-frequency electrical stimulation. Electrophysiological assay indicated that HWTX-XVI specifically inhibited N-type calcium channels in rat dorsal root ganglion cells (IC50 ∼60 nM). The inhibitory effect of HWTX-XVI on N-type calcium channel currents was dose-dependent and similar to that of CTx-GVIA and CTx-MVIIA. However, the three peptides exhibited markedly different degrees of reversibility after block. The toxin had no effect on voltage-gated T-type calcium channels, potassium channels or sodium channels. Intraperitoneal injection of the toxin HWTX-XVI to rats elicited significant analgesic responses to formalin-induced inflammation pain. Toxin treatment also changed withdrawal latency in hot plate tests. Intriguingly, we found that intramuscular injection of the toxin reduced mechanical allodynia induced by incisional injury in Von Frey test. Thus, our findings suggest that the analgesic potency of HWTX-XVI and its greater reversibility could contribute to the design of a novel potential analgesic agent with high potency and low side effects. PMID:24467846

  7. [Effect of calcium on medium alkalinization induced by salicylic acid in Salvia miltiorrhiza suspension cultures].

    Science.gov (United States)

    Liu, Liancheng; Wang, Cong; Dong, Juan'e; Su, Hui; Zhuo, Zequn; Xue, Yaxin

    2013-07-01

    We studied medium alkalinization in Salvia miltiorrhiza suspension cultures treated with salicylic acid and the effect of Ca2+ in this process through application of calcium channel antagonists (Verapamil, LaCl3, LiCl, 2-APB) and ionophore A23187. The results show that salicylic acid could induce significant medium alkalinization in S. miltiorrhiza culture. Verapamil and LaCl3 or LiCl and 2-APB, two different groups of calcium channel antagonist, significantly inhibited the medium alkalinization induced by salicylic acid. However, the suppression effect of verapamil or LaCl3 on medium alkalinization induced by salicylic acid was higher than that of LiCl or 2-APB. When two types of calcium channel inhibitor (LaCl3 and 2-APB) were used together, the medium alkalinization induced by salicylic acid was completely suppressed and even reduced the pH in medium. On the other hand, A23187 could promote the medium alkalinization. Based on the results above, we speculated that salicylic acid could induce significant medium alkalinization in S. miltiorrhiza culture, depending on the calcium from both extracell and intracell. Moreover, calcium from extracell plays a more dominant role in this process. Reveal of relationship in this research between Ca2+ and medium alkalinization can provide theory evidence for mechanism of the plant secondary metabolism.

  8. The L-Type Calcium Channel Blocker Nifedipine Impairs Extinction, but Not Reduced Contingency Effects, in Mice

    Science.gov (United States)

    Jami, Shekib; Barad, Mark; Cain, Christopher K.; Godsil, Bill P.

    2005-01-01

    We recently reported that fear extinction, a form of inhibitory learning, is selectively blocked by systemic administration of L-type voltage-gated calcium channel (LVGCC) antagonists, including nifedipine, in mice. We here replicate this finding and examine three reduced contingency effects after vehicle or nifedipine (40 mg/kg) administration.…

  9. The effect of dimethylsulfoxide on the calcium paradox.

    OpenAIRE

    Ruigrok, T. J.; Moes, D.; Slade, A.M.; Nayler, W. G.

    1981-01-01

    Reperfusion of isolated rat hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). Experiments were undertaken to study the effect of dimethylsulfoxide (DMSO) on the occurrence of the calcium paradox in rat heart muscle. DMSO (1.4 mol/l) was added to the calcium-free or the reperfusion medium. Cell damage was quantitated in terms of creatine kinase (CK) release, cardiac electrogram (CEG) changes, and ultras...

  10. [The clinical pharmacology and efficacy of the new Soviet calcium antagonist foridon].

    Science.gov (United States)

    Kukes, V G; Rumiantsev, A S; Gneushev, E T; Al'perovich, B R; Svetyĭ, L I; Nasyrov, M N; Taratuta, T V

    1990-01-01

    A total of 56 patients with coronary heart disease (CHD), angina pectoris of effort, functional classes II-III, were placed under observation. All the patients received 20 mg foridon (F), 20 mg corinfar (C), 80 mg anapriline (A). 24 patients were subjected to the continuous treatment with F (20 mg 4 times a day). The antianginal action of the drug was compared to the blood concentration on days 7, 14, 21, 28, 43 and 57 of the treatment with F. In 14 patients with angina pectoris and in 18 patients with essential hypertension, the efficacy of F and C was cross correlated. It has been demonstrated that F can be successfully used for the treatment of patients with CHD, angina pectoris of effort and (or) essential hypertension. The increase of the single dose of foridon from 20 to 40 mg does not result in the potentiation of its hypotensive effect. F and C provoke the highest rise of exercise tolerance with combined angina pectoris. Continuous concomitant administration of F and C with A leads to the potentiation of the antianginal action. PMID:2084878

  11. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    Science.gov (United States)

    Casillas-Espinosa, Pablo Miguel; Hicks, Ashleigh; Jeffreys, Amy; Snutch, Terrance P; O'Brien, Terence J; Powell, Kim L

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg) was assessed in fully kindled rats (5 class V seizures) as compared to vehicle, ethosuximide (ETX, 100mg/kg) and carbamazepine (30mg/kg). Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg), ETX (100mg/kg) or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (pkindled state (pkindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  12. Effects of Adding Chymosin to Milk on Calcium Homeostasis

    DEFF Research Database (Denmark)

    Møller, Ulla Kristine; Jensen, Lars Thorbjørn; Mosekilde, Leif;

    2014-01-01

    Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome...... of the study was 24-h renal calcium excretion that is considered a proxy measure of the amount of calcium absorbed from the intestine. We studied 125 healthy men and women, aged 34 (25-45) years on two separate days. On each day, a light breakfast was served together with 500 ml of semi-skimmed milk to which...... not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further...

  13. Coupling Effect of Ion Channel Clusters on Calcium Signalling

    International Nuclear Information System (INIS)

    Based on a modified intracellular Ca2+ model involving diffusive coupling of two calcium ion channel clusters, the effects of coupling on calcium signalling are numerically investigated. The simulation results indicate that the diffusive coupling of clusters together with internal noise determine the calcium dynamics of single cluster, and for either homogeneous or heterogeneous coupled clusters, the synchronization of clusters, which is important to calcium signalling, is enhanced by the coupling effect

  14. Coupling Effect of Ion Channel Clusters on Calcium Signalling

    Institute of Scientific and Technical Information of China (English)

    TANG Jun; JIA Ya; YI Ming; MA Jun; YU Guang

    2008-01-01

    @@ Based on a modified intracellular Ca2+ model involving diffusive coupling of two calcium ion channel clusters,the effects of coupling on calcium signalling are numerically investigated.The simulation results indicate that the diffusive coupling of clusters together with internal noise determine the calcium dynamics of single cluster,and for either homogeneous or heterogeneous coupled clusters,the synchronization of clusters,which is important to calcium signalling,is enhanced by the coupling effect.

  15. Impact of Trichoderma spp. on Soybean Seed Germination and Potential Antagonistic Effect on Sclerotinia sclerotiorum

    OpenAIRE

    Sonja Tančić; Jelica Skrobonja; Mirjana Lalošević; Radivoje Jevtić; Miloš Vidić

    2013-01-01

    Trichoderma species have been registered as species with important plant growth promoting potential and antagonistic effect against various phytopathogens. Trichoderma isolates originating from different soil types from the Vojvodina region (Serbia) were screened using dual culture test for their antagonistic effect against the pathogen Sclerotinia sclerotiorum. All tested isolates had high radial growth inhibition (RGI) factors of the pathogen and high col...

  16. [Vascular calcifications, the hidden side effects of vitamin K antagonists].

    Science.gov (United States)

    Bennis, Youssef; Vengadessane, Subashini; Bodeau, Sandra; Gras, Valérie; Bricca, Giampiero; Kamel, Saïd; Liabeuf, Sophie

    2016-09-01

    Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA. This is the case of matrix Gla-protein (MGP), a protein that plays a major inhibitory role in the development of vascular calcifications. Several experimental and epidemiological results suggest that the use of the VKA could promote the development of vascular calcifications increasing thus the cardiovascular risk. This risk seems to be higher in patients with chronic kidney disease or mellitus diabetes who are more likely to develop vascular calcifications, and may be due to a decrease of the MGP activity. This review aims at summarizing the data currently available making vascular calcifications the probably underestimated side effects of VKA.

  17. Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    A. Rodriguez-Barbero

    1992-01-01

    Full Text Available To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-β-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.

  18. Effect of L-lactic acid on calcium absorption in rats fed omeprazole.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Yasui, H; Watanuki, M

    1998-06-01

    We examined the effect of L-lactic acid on calcium absorption in male Wistar rats made achlorhydric by dietary omeprazole, a proton pump inhibitor. The dietary omeprazole intake (0.03 g/100 g of diet) increased the gastric pH and decreased the apparent calcium absorption ratio. Dietary famotidine (0.03 g/100 g of diet), an H2-receptor antagonist, and lower doses of omeprazole (0.005 or 0.01 g/100 g of diet) did not affect the gastric pH or the calcium absorption. In a second experiment, dietary lactic acid (0.5, 1.0, or 2.5 g/100 g of diet) increased the intestinal calcium absorption dose dependently in rats fed omeprazole (0.03 g/100 g of diet). The gastric pH was significantly decreased only in the rats fed higher doses of lactic acid (1.0, or 2.5 g/100 g of diet). In a third experiment, a dietary sour milk beverage containing lactic acid (0.5 g/100 g of diet) increased the intestinal calcium absorption, but did not affect the gastric pH in rats fed omeprazole (0.03 g/100 g of diet). Although the significance of gastric acid in terms of overall calcium absorption is not known, under the present experimental conditions, the inhibition of gastric acid secretion by dietary omeprazole decreased the apparent calcium absorption, and the dietary lactic acid prevented the calcium absorption in rats fed omeprazole.

  19. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    Directory of Open Access Journals (Sweden)

    Pablo Miguel Casillas-Espinosa

    Full Text Available Temporal lobe epilepsy (TLE is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg was assessed in fully kindled rats (5 class V seizures as compared to vehicle, ethosuximide (ETX, 100mg/kg and carbamazepine (30mg/kg. Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg, ETX (100mg/kg or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05, IV (p<0.01 or V (p<0.0001 seizure, and to reach a fully kindled state (p<0.01, than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  20. Effect of combining different calcium concentration dialysate on calcium balance in peritoneal dialysis patients

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hui-ping; WU Bei; LU Li-xia; QIAO Jie; WU Xiang-lan; WANG Mei

    2012-01-01

    Background Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality.Therefore,maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone(iPTH)level has become the focus of attention.We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis(CAPD)patients.Methods Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate(DCa1.25,PD4,22 patients)or a combination of 1.75 mmol/L calcium dialysate(DCa1.75,PD2)and PD4(18 patients)twice a day respectively.Total serum calcium(after albumin correction),serum phosphorus,iPTH,alkaline phosphatase(ALP)and blood pressure were recorded before and 1,3 and 6 months after treatment commenced.Results No significant difference was found in baseline serum calcium,phosphorus between the two patient groups,but the levels of iPTH were significantly different.No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months.In the PD4 group,serum calcium level at the 1st,3rd,6th months were significantly lower than the baseline(P<0.05).There was no significant difference in serum phosphorus after 6 months treatment.iPTH was significantly higher(P<0.001)at the 1st,3rd,and 6th months compared with the baseline.No differences were seen in ALP and blood pressure.In the PD4+PD2 group,no significant changes in serum calcium,phosphorus,iPTH,ALP and BP during the 6-month follow-up period.Conclusions Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium,increase iPTH,without change in serum phosphorus,ALP,and BP.The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.

  1. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  2. Effects of alpha 1-adrenoceptor antagonists on male sexual function

    NARCIS (Netherlands)

    M.M. van Dijk; J.J.M.C.H. de la Rosette; M.C. Michel

    2006-01-01

    alpha(1)-Adrenoceptor antagonists such as alfuzosin, doxazosin, tamsulosin and terazosin are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), but are only second-line agents (doxazosin and terazosin only) for the treatment of arter

  3. Protective effects of calmodulin antagonists (trifluoperazine and W-7 on hypothermic ischemic rat hearts.

    Directory of Open Access Journals (Sweden)

    Sugawara,Eiji

    1991-06-01

    Full Text Available The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP and N-(6-aminohexyl-5-chloro-1-naphthalene sulfonamide (W-7 was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.

  4. Effects of calcium gluconate on the utilization of magnesium and the nephrocalcinosis in rats fed excess dietary phosphorus and calcium.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Kado, S; Nagata, Y; Kimura, H; Uchida, K; Watanuki, M

    1996-08-01

    The effects of calcium gluconate on the utilization of magnesium and nephrocalcinosis in male Wistar rats made magnesium-deficient by adding excess dietary phosphorus (1.195 g of phosphorus/100 g of diet) and calcium (1.04 g of calcium/100 g of diet) were compared with the effects of calcium carbonate. The effects of dietary magnesium concentration on the magnesium status and nephrocalcinosis were also examined. Adding excess dietary phosphorus and calcium decreased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur and increased the deposition of calcium in the kidney, and the low magnesium condition (0.024 g of magnesium/100 g of diet) aggravated the deposition of calcium and the low magnesium status. The apparent magnesium absorption ratios and femur magnesium concentration in the rats fed a calcium gluconate diet (an equimolar mixture of calcium gluconate and calcium carbonate was used as a source of calcium) were significantly higher than in the rats fed a calcium carbonate diet (only calcium carbonate was used as a source of calcium), irrespective of dietary magnesium concentration. Dietary calcium gluconate lessened the accumulation of calcium in the kidney and increased the serum magnesium concentration compared with dietary calcium carbonate, when the rats were fed the normal magnesium diet (0.049 g of magnesium/100 g of diet) but not the low magnesium diet. We speculate that the increased utilization of magnesium by feeding the calcium gluconate diet to a limited extent prevented the low magnesium status and the severity of nephrocalcinosis caused by adding excess dietary phosphorus and calcium.

  5. Effect of calcium on moving-bed biofilm reactor biofilms.

    Science.gov (United States)

    Goode, C; Allen, D G

    2011-03-01

    The effect of calcium concentration on the biofilm structure, microbiology, and treatment performance was evaluated in a moving-bed biofilm reactor. Three experiments were conducted in replicate laboratory-scale reactors to determine if wastewater calcium is an important variable for the design and optimization of these reactors. Biofilm structural properties, such as thickness, oxygen microprofiles, and the composition of extracellular polymeric substances (EPS) were affected by increasing calcium concentrations. Above a threshold concentration of calcium between 1 and 50 mg/L, biofilms became thicker and denser, with a shift toward increasingly proteinaceous EPS at higher calcium concentrations up to 200 mgCa2+/L. At 300 mgCa2+/L, biofilms were found to become primarily composed of inorganic calcium precipitates. Microbiology was assessed through microscopy, denaturing grade gel electrophoresis, and enumeration of higher organisms. Higher calcium concentrations were found to change the bacterial community and promote the abundant growth of filamentous organisms and various protazoa and metazoan populations. The chemical oxygen demand removal efficiency was improved for reactors at calcium concentrations of 50 mg/L and above. Reactor effluents for the lowest calcium concentration (1 mgCa2+/L) were found to be turbid (>50 NTU), as a result of the detachment of small and poorly settling planktonic biomass, whereas higher concentrations promoted settling of the suspended phase. In general, calcium was found to be an important variable causing significant changes in biofilm structure and reactor function.

  6. Effects of certain muscarinic antagonists on the actions of anticholinesterases on cat skeletal muscle.

    Science.gov (United States)

    Brimblecombe, R W; French, M C; Webb, S N

    1979-04-01

    1. The effects of some muscarinic antagonists, namely, N-ethyl-2-pyrrolidylmethyl-cyclopentylphenyl glycollate (PMCG), N-methyl-4-piperidyl-phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4'-N-methyl-piperidyl-1-phenyl-cyclopentane carboxylate (G3063) on organophosphate (sarin, soman)- and carbamate (neostigmine)-induced twitch augmentation have been studied in cat soleus muscle. 2. The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function. 3. The muscarinic antagonists studied were capable of preventing or reversing sarin-, soman- or neostigmine-induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle. 4. The protective action of these muscarinic antagonists is dose-dependent but independent of known antagonist actions at muscarinic receptors. 5. The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action. PMID:435681

  7. Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

    Science.gov (United States)

    Weems, Y S; Randel, R D; Carstens, G E; Welsh, T H; Weems, C W

    2004-04-01

    The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186-245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 degrees C under 95% air: 5% CO2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP3; PGE2; CaCl2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17beta; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE2 and PGF2alpha by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 x 2 x 21). Since hormone data secreted by placental tissue in vitro did not differ (P > or = 0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE2 in uterine venous blood were two-fold greater (P Angus than Brahman cows. PGE2 and PGF2alpha in vehicle controls increased from 4 to 8h (P or = 0.05) Progesterone in culture media treated with RU-486 increased (P or = 0

  8. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2008-01-01

    Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  9. Effects of opiate antagonists on hormones and behavior of male and female rhesus monkeys.

    Science.gov (United States)

    Abbott, D H; Holman, S D; Berman, M; Neff, D A; Goy, R W

    1984-02-01

    Opiate antagonists, naloxone (100 micrograms/kg) and naltrexone (1 mg/kg) were given to singly housed adult male or female rhesus prior to a 20-minute behavioral test with an oppositely sexed stimulus monkey. Four of the intact adult males were socially and sexually experienced. The remaining two intact males and two castrated males had been reared in socially restricted conditions and were psychosexually deficient. Adult females were ovariectomized, and the effects of opiate antagonists were examined with or without concurrent estradiol treatment. Both antagonists inhibited sexual behavior of the socially reared, sexually active, intact males. No stimulatory effects on sexual behavior were observed for sexually deficient males, whether intact or castrated. Females showed little change in sexual behavior following opiate antagonist treatment, regardless of endocrine status. The proportion of approaches of the female to the male was increased when naloxone, but not naltrexone, was given. Specific endocrine effects of the opiate antagonists were only found in intact males. Naltrexone significantly increased LH concentrations in the two males tested, while the increase in LH in the four males receiving naloxone was not significant. In all intact males, increases in LH were accompanied by statistically significant increases in circulating concentrations of testosterone following naloxone and naltrexone. The gonadotropic stimulating effect of the opiate antagonists was specific to LH, and no changes were observed in circulating concentrations of FSH in either sex. PMID:6424632

  10. Effect of galactooligosaccharides on calcium absorption in rats.

    Science.gov (United States)

    Chonan, O; Watanuki, M

    1995-02-01

    The effect of transgalactosylated oligosaccharides (TOS), which are oligosaccharides that are unhydrolyzed in the small intestine and are fermented by the intestinal bacteria, on calcium absorption was examined in male Wistar rats for 10 days. The apparent calcium absorption ratios and the apparent retention ratios were significantly higher in the rats fed TOS-containing diets (5 or 10 g/100 g of diet). In the second experiment, the cecum was ligated in situ and calcium absorption from the cecum was observed after injecting TOS into the cecal lumen. Four hours after the injection, the calcium concentration in the cecal vein of the rats given TOS was significantly higher than that of the control. The calcium content in the liquid phase of the cecal lumen and the liquid phase weight were also increased by the injection of TOS into the cecum. Although the extent of calcium absorption from the cecum of rats fed TOS is due to overall calcium absorption is not known, under the experimental conditions used in the present study the stimulatory effect of TOS on calcium absorption may be partly associated with increased solubility of calcium and the fluid content in the intestinal lumen.

  11. Effect of three different calcium hydroxide mixtures (calcium hydroxide with glycerine, normal saline and distilled water) on root dentin microhardness

    OpenAIRE

    Hasheminia SM; Norouzynasab S

    2007-01-01

    Background and Aim: During root canal therapy, it is necessary to remove as many bacteria as possible from the root canal. The use of medicaments is recommended to reduce the microbial population prior to root filling. Calcium hydroxide pastes have been used because of their antibacterial effects and the ability of tissue dissolving. The aim of this study was to evaluate the effect of calcium hydroxide/glycerine mixture, calcium hydroxide/normal saline mixture and calcium hydroxide/distilled ...

  12. An integrated multiassay approach to the discovery of small-molecule N-type voltage-gated calcium channel antagonists.

    Science.gov (United States)

    Finley, Michael F A; Lubin, Mary Lou; Neeper, Michael P; Beck, Edward; Liu, Yi; Flores, Christopher M; Qin, Ning

    2010-12-01

    Abstract The N-type voltage-gated calcium channel (Cav2.2) has been intensively explored as a target for novel, small-molecule analgesic drugs because of its distribution in the pain pathway and its role in nociceptive processing. For example, Cav2.2 is localized at presynaptic terminals of pain fibers in the dorsal horn, and it serves as a downstream effector of μ-opioid receptors. Most importantly, antagonism of the channel by the highly specific and potent Cav2.2 blocker ω-conotoxin MVIIA (ziconotide) produces clinical efficacy in the treatment of severe, intractable pain. To identify novel small-molecule Cav2.2 inhibitors, we developed new tools and screening methods critical to enhance the efficiency and probability of success. First, we established and characterized a new cell line stably expressing the three subunits of the Cav2.2, including an α-subunit splice variant that is uniquely expressed by dorsal root ganglion neurons. Second, using this cell line, we validated and employed a fluorescence-based calcium flux assay. Third, we developed a new "medium-throughput" electrophysiology assay using QPatch-HT to provide faster turnaround on high-content electrophysiology data that are critical for studying ion channel targets. Lastly, we used a therapeutically relevant, ex vivo spinal cord calcitonin gene-related peptide-release assay to confirm activities in the other assays. Using this approach we have identified compounds exhibiting single-digit nM IC₅₀ values and with a positive correlation across assay methods. This integrated approach provides a more comprehensive evaluation of small-molecule N-type inhibitors that may lead to improved therapeutic pharmacology. PMID:21050074

  13. [3H]TA-3090, a selective benzothiazepine-type calcium channel receptor antagonist: In vitro characterization

    International Nuclear Information System (INIS)

    Binding of the new benzothiazepine calcium channel blocker, (+)-(2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2- (4- methoxyphenyl)-1,5-benzothiazepine-4-(5H)-one maleate, [3H]TA-3090, was characterized and its specificity for rat myocardial benzothiazepine receptors described. Scatchard plots and nonlinear regression analysis of specific [3H]TA-3090 binding best fit a one-site binding model (Kd = 8.8 +/- 2.7 nM, Bmax = 132 +/- 38 fmol/mg protein). Kinetically derived affinity constants were in close agreement (Kd = 7.86 nM) with those obtained from analysis of equilibrium binding data. In comparison, under identical conditions [3H]diltiazem exhibited a Kd of 38 nM and Bmax, 106 fmol/mg protein. Specific binding was saturable, reversible and stereoselective (d-cis-TA-3090 Ki = 14 nM; 1-cis-TA-3090 Ki = 2700 nM). Competitions for [3H]TA-3090 binding were conducted with nifedipine, propranolol, prazosin, quinuclidinyl benzilate, verapamil and yohimbine. Only the calcium channel blockers nifedipine and verapamil inhibited specific [3H]TA-3090 binding. Nifedipine could maximally inhibit only 52% of specifically bound [3H]TA-3090 at 10 microM. In contrast, however, 10 microM verapamil completely inhibited specific radioligand binding (Ki = 93 +/- 28 nM) but with six times less efficacy than TA-3090. Thus, these data demonstrate that [3H]TA-3090 is a potent radioligand selective for the benzothiazepine binding site and is consistent with the hypothesis that [3H]TA-3090 interacts with a myocardial benzothiazepine receptor site

  14. CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

    Science.gov (United States)

    Mamedova, Liaman; Capra, Valérie; Accomazzo, Maria Rosa; Gao, Zhan-Guo; Ferrario, Silvia; Fumagalli, Marta; Abbracchio, Maria P.; Rovati, G. Enrico; Jacobson, Kenneth A.

    2016-01-01

    Montelukast and pranlukast are orally active leukotriene receptor antagonists selective for the CysLT1 receptor. Conversely, the hP2Y1,2,4,6,11,12,13,14 receptors represent a large family of GPCRs responding to either adenine or uracil nucleotides, or to sugar-nucleotides. Montelukast and pranlukast were found to inhibit nucleotide-induced calcium mobilization in a human monocyte-macrophage like cell line, DMSO-differentiated U937 (dU937). Montelukast and pranlukast inhibited the effects of UTP with IC50 values of 7.7 and 4.3 μM, respectively, and inhibited the effects of UDP with IC50 values of 4.5 and 1.6 μM, respectively, in an insurmountable manner. Furthermore, ligand binding studies using [3H]LTD4 excluded the possibility of orthosteric nucleotide binding to the CysLT1 receptor. dU937 cells were shown to express P2Y2, P2Y4, P2Y6, P2Y11, P2Y13 and P2Y14 receptors. Therefore, these antagonists were studied functionally in a heterologous expression system for the human P2Y receptors. In 1321N1 astrocytoma cells stably expressing human P2Y1,2,4,6 receptors, CysLT1 antagonists inhibited both the P2Y agonist-induced activation of phospholipase C and intracellular Ca2+ mobilization. IC50 values at P2Y1 and P2Y6 receptors were astrocytoma cells expressing an endogenous M3 muscarinic receptor, 10 μM montelukast had no effect on the carbachol-induced rise in intracellular Ca2+. These data demonstrated that CysLT1 receptor antagonists interact functionally with signaling pathways of P2Y receptors, and this should foster the study of possible implications for the clinical use of these compounds in asthma or in other inflammatory conditions. PMID:16280122

  15. Studies on the Calcium Antagonist Action of Arctigenin%牛蒡苷元钙拮抗作用的研究(英文)

    Institute of Scientific and Technical Information of China (English)

    高阳; 康廷国; 张效禹

    2000-01-01

    The calcium antagonist action of arctigenin (ACT) was studied in order to verify the ef-fect of Fructus Arctii for the relieve of exterior syndrome. Muscular contraction of isolated rat trachea,colon, pulmonary artery and thoracic aorta induced by KC1, that of guinea pig trachea induced by CaCI2,before and after the addition of ACT were assessed and their contraction-response curves drawn and PD'2calculated according to Scott. The inhibition rate of two-phase contraction of guinea pig trachea induced byacetylcholine chloride (Ach) in comparison with verapamil (VER) was calculated. Results of the studyshowed that ACT could non-compatitively antagonize the muscular contraction of the test specimens withPD'2 of 4.01, 5.11, 5.98 and 6.05 respectively. Similar to VER, ACT could non-competitively antagonizethe isolated guinea pig trachea with PD'2 of 4.04 and 5.62 respectively. Both of them could inhibit thefirst phase contraction induced by Ach with inhibition rates of 66.14% and 81.42% respectively. It wasconcluded that ACT, as the active constituent of Fructus Arctii, relaxed smooth muscle contraction byblocking the potential dependant Ca2+ channel and the internal release of Ca2+.%对牛蒡苷元(ACT)的钙拮抗作用进行探讨,为确认ACT是牛蒡子解表功能的有效成分提供实验依据。描记给ACT前后,各标本对KCl或CaCl2诱发收缩的量效曲线,按Scott法计算PD'2;测定给ACT后,标本对乙酰胆硷(Ach)诱发的两相收缩的抑制百分率。ACT对离体大鼠气管、结肠、肺动脉、胸主动脉平滑肌由KCl引起的收缩产生非竞争性拮抗作用,其PD'2分别为4.01,5.11,5.98,6.05 ACT和维拉帕米(Verapamil)相似,对离体豚鼠气管平滑肌由CaCl2引起的收缩产生非竞争性拮抗作用,其PD'2分别为4.04,5.62;对Ach诱发的两相收缩只明显抑制第一时相收缩,抑制率分别为66.14%,8L 42%.ACT对平滑肌的松弛作用可能是由于阻滞电

  16. The Effect of U50488 on the Cardiac Rhythm and Intracellular Calcium in the Rat Heart.

    Institute of Scientific and Technical Information of China (English)

    Zhang Weimin; Xin Dalin; Wong Takming

    2000-01-01

    The effect of U50488, a selective k-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed that U50488 can induce arrhythmias dose-dependently in the isolated perfused rat heart and increase [Ca2+] i in the single ventricular myocyte. The effect of U50488 can be blocked by a selectivek-receptor antagonist, nor-binaltorphimine.The arrhythmogenic effects and the increase of [ Ca2 + ] i induced by U50488 were blocked by U73122, neomycin and streptomycin, which are selective phospolipase C inhibitors, but not by U73433, the inactive structural analog of U73122. These results demonstrated that the arrhythmogenic effect of cardiac k-receptor is due to activation of phosphoinositol/Ca2+ pathway.

  17. Genetic determinants of response and adverse effects following vitamin K antagonist oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Parameshwar S.

    2016-06-01

    Full Text Available Background: Vitamin K antagonist anticoagulants (warfarin/acenocoumarol are commonly used anticoagulants that require careful clinical management to balance the risks of over anticoagulation and bleeding with those of under anticoagulation and clotting. Genetic variants of the enzyme that metabolizes vitamin K antagonist anticoagulant, cytochrome P-450 2C9 (CYP2C9, and of a key pharmacologic target of vitamin K antagonists anticoagulant, vitamin K epoxide reductase (VKORC1, contribute to differences in patients responses to various anticoagulant doses. Methods: In thirty patients on oral vitamin K antagonist anticoagulant therapy, presented with either clotting manifestations (valve thrombosis, pulmonary embolism and DVT or prolonged INR/bleeding manifestations, we assessed CYP2C9 genotypes, VKORC1 haplotypes, clinical characteristics, response to therapy (as determined by the international normalized ratio [INR], and bleeding events. Results: Of the thirty patients, thirteen patients INR was high and four patients presented with major bleeding and four with minor bleeding manifestations. Out of thirteen patients with high INR, ten patients showed CYP2C9 polymorphism ( 1/ 3 and 2/ 3 of poor metabolizer genotype. Most of the high INR patients were recently started on oral vitamin K antagonist anticoagulant. Most patients presented with clotting manifestations with below therapeutic INR are noncompliant with anticoagulants. Conclusions: The results of this study suggest that the CYP2C9 polymorphisms are associated with an increased risk of over anticoagulation and of bleeding events among patients on vitamin K antagonists' anticoagulant setting. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving vitamin K antagonist anticoagulants. However the cost-effectiveness of genotyping of patients must be considered. [Int J Res Med Sci

  18. Tree species effects on calcium cycling: The role of calcium uptake in deep soils

    NARCIS (Netherlands)

    Dijkstra, F.A.; Smits, M.M.

    2002-01-01

    Soil acidity and calcium (Ca) availability in the surface soil differ substantially beneath sugar maple (Acer saccharum) and eastern hemlock (Tsuga canadensis) trees in a mixed forest in northwestern Connecticut. We determined the effect of pumping of Ca from deep soil (rooting zone below 20-cm mine

  19. Effect of lactose on intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Calcium absorption was immediately increased when lactose was administered in large amounts in the intestine of standard rats fed on a vitamin D diet. The same effect could be reproduced with lactulose, a glucid un-hydrolyzed by lactase and unabsorbed. The occurrence of a saturation process for high doses of calcium agrees with a biochemical process through a carrier; this process was not inhibited by actinomycin D, which does not agree with a 'de novo' synthesis of a calcium binding protein; yet activation of the preexisting protein cannot be excluded. The intestinal effect of lactose resulted in an inhibition of bone catabolism in the adult normocalcemic rat indicating a possible interference of thyrocalcitonin. Finally in the young rat, hypocalcemic by lack of vitamin D, on account of the lactose effect, calcium can be considered as a 'third messenger' in the chain of intracellular events between the interaction of the parathyroid hormone with the bone receptor and the expression of its activity. (author)

  20. Effect of the cannabinoid receptor-1 antagonist rimonabant on lipolysis in rats

    DEFF Research Database (Denmark)

    Mølhøj, Signe; Hansen, Harald S; Schweiger, Martina;

    2010-01-01

    The cannabinoid receptor 1 antagonist, rimonabant, reduces food intake and body weight, but contradictory findings have been reported as to whether the weight-reducing effect is fully accounted for by the reduced food intake or if rimonabant also mediates a lipolytic effect. In the present study...

  1. Effects of Exterior Abscisic Acid on Calcium Distribution of Mesophyll Cells and Calcium Concentration of Guard Cells in Maize Seedlings

    Institute of Scientific and Technical Information of China (English)

    GUO Xiu-lin; MA Yuan-yuan; LIU Zi-hui; LIU Bin-hui

    2008-01-01

    In this study, the direct effects of exterior abscisic acid (ABA) on both calcium distribution of mesophyll cells and cytosolic calcium concentration of guard cells were examined. The distribution of Ca2+ localization were observed with calcium antimonate precipitate-electromicroscopic-cyto-chemical methods after treated with ABA and pretreated with ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), verapamil (Vp), and trifluoperazine (TFP). The laser scanning confocal microscopy was used to measure the cytosolic calcium concentrations of guard cells under different treatments. The results showed that the cytosolic Ca2+ concentration of mesophyll cells was induced to increase by ABA, but to decrease in both outside cell and the vacuoles within 10 min after treatments. The cytosolic calcium concentration of guard cells was increased gradually with the lag in treatment time. However, both EGTA and TFP could inverse those effects, indicating that the increase of cytosolic calcium induced by exterior ABA was mainly caused by calcium influx. The results also showed that calmodulin could influence both the calcium distribution of mesophyll cells and calcium concentration of guard cells. It shows that calmodulin participates in the process of ABA signal transduction, but the mechanism is not known as yet. The changes both calcium distribution of mesophyll cells and calcium concentration of guard cells further proved that the variations of cytosolic Ca2+ concentration induced by ABA were involved in the stomatal movements of maize seedlings.

  2. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  3. Effect of calmodulin antagonists on contraction and45Ca movements in rat aorta

    NARCIS (Netherlands)

    Wermelskirchen, D.; Koch, P.; Wilhelm, D.; Nebel, U.; Leidig, A.; Wilffert, B.; Peters, Thies

    1989-01-01

    To study the selectivity of calmodulin antagonists it was assumed that they should inhibit noradrenaline (NA)- and K+-induced contractions similarly without an accompanying inhibition of45Ca uptake. Therefore, in isolated rat aorta the effects of W-7, calmidazolium and trifluoperazine on contraction

  4. Effect of the Urotensin Receptor Antagonist Palosuran in Hypertensive Patients With Type 2 Diabetic Nephropathy

    NARCIS (Netherlands)

    L. Vogt; C. Chiurchiu; H. Chadha-Boreham; P. Danaietash; J. Dingemanse; S. Hadjadj; H. Krum; G. Navis; E. Neuhart; A.I. Parvanova; P. Ruggenenti; A.J. Woittiez; R. Zimlichman; G. Remuzzi; D. de Zeeuw

    2010-01-01

    The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion an

  5. EFFECTS OF THE ANGIOTENSIN-II ANTAGONIST LOSARTAN IN HYPERTENSIVE PATIENTS WITH RENAL-DISEASE

    NARCIS (Netherlands)

    GANSEVOORT, RT; DEZEEUW, D; SHAHINFAR, S; REDFIELD, A; DEJONG, PE

    1994-01-01

    Objective: To study the effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease. Design: A single-blind longitudinal study was performed, lasting 4 months. Patients were treated once a day with placebo, 50 mg losartan, 100 mg losartan and placebo, each for 1 mon

  6. Therapeutic effect of pranlukast, a cysteinyl leukotriene receptor antagonist, on focal cerebral ischemia in mice

    Institute of Scientific and Technical Information of China (English)

    XUQiu-Qin; WEIEr-Qing; YUYue-Ping; ZHANGQi; ZHANGShi-Hong; ZHUChao-Yang

    2004-01-01

    AIM: To determine whether pranlukast (ONO-1078 ), a cysteinyl leukotriene receptor antagonist, possesses therapeutic effect when administered after focal cerebral ischemia in mice. METHODS: Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion, pranlukast and edaravone, a positive control drug, were ip injected 1, 6 and

  7. Effect of resorbable calcium aluminate ceramics on regulation of calcium and phosphorus in rats.

    Science.gov (United States)

    Carvalho, B A; Bajpai, P K; Graves, G A

    1976-06-01

    Ions released from resorbable ceramics could be toxic to the animal. Experiments were designed to study the effect of implanting three different weights of porous resorbable calcium aluminate ceramics (0.172, 0.332, and 0.504 g) in rats for a total duration of 300 days. Gross and microscopic examination of heart, liver, kidneys, trachea with thyroid, and muscle adjacent to the implant did not show any pathological changes. Calcium and inorganic phosphate content of bone, serum and urine were not affected by the implants. Urine hydroxyproline excretion did not change in the animals implanted with ceramics. Animals implanted with 0.332 g of ceramics had a significantly higher serum alkaline phosphatase activity than the control animals. Resorption of calcium and depositon of inorganic phosphates in the implanted ceramics suggested that ions were being exchanged with the body fluids. Implantation of 0.172 to 0.332 g porous resorbable calcium aluminate ceramic was not toxic to the animal.

  8. Effect of nano-calcium-enriched milk on calcium metabolism in ovariectomized rats.

    Science.gov (United States)

    Park, Heung-Sik; Ahn, Joungjwa; Kwak, Hae-Soo

    2008-09-01

    This study was designed to examine the effect of different kinds of calcium enrichment on serum and urine indices of mineral status in ovariectomized rats. Twenty-four 7-week-old Sprague-Dawley female rats were divided into four groups, ovariectomized, and fed diets containing the following: (1) Control, non-Ca-enriched milk; (2) OVX1, calcium carbonate-enriched milk; (3) OVX2, ionized Ca-enriched milk; and (4) OVX3, nano-Ca-enriched milk. After 18 weeks of feeding, the food efficiency ratio in the nano-Ca-fed group was significantly lower compared with those in the Control and OVX2 groups. There was no difference in serum and fecal Ca among the groups. The bone/total alkaline phosphatase ratio was significantly higher in rats fed milk enriched with nano-Ca (59%) and calcium carbonate (62%) than in control (44%) animals. Urinary Ca was the highest in the nano-Ca-enriched group; however, urinary excretions of deoxypyridinoline and hydroxyproline were significantly decreased in the nano-Ca-enriched group. The present results indicate that consumption of nano-Ca-enriched milk resulted in an increase of urinary excretion of calcium and a decrease in deoxypyridinoline and hydroxyproline in ovariectomized rats.

  9. Infusions of alpha-2 noradrenergic agonists and antagonists into the amygdala: effects on kindling.

    Science.gov (United States)

    Pelletier, M R; Corcoran, M E

    1993-12-31

    We reported previously that activation of alpha-2 adrenoceptors with infusions of clonidine into the amygdala/pyriform region is sufficient to retard kindling. To characterize further the involvement in kindling of alpha-2 receptors in the amygdala/pyriform, we exposed rats to unilateral intraamygdaloid infusions of a variety of noradrenergic drugs followed by either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Infusions and electrical stimulation were administered once every 48 h. The prophylactic effects of clonidine were blocked by simultaneous infusion of idazoxan, an alpha-2 adrenergic antagonist, which suggests strongly that these effects were produced at an alpha-2 receptor. Intraamygdaloid infusions of xylazine, another alpha-2 agonist, also significantly retarded low-frequency kindling. Unexpectedly, intraamygdaloid infusions of the alpha-2 antagonists idazoxan, yohimbine, and SK&F 104856 failed to accelerate kindling. Infusion of the alpha-1 antagonist corynanthine also failed to affect kindling. We propose that the alpha-2 adrenoceptors in the amygdala/pyriform region contribute to the prophylactic effects of systemically administered clonidine and that the facilitation of kindling observed after systemic administration of alpha-2 antagonists may be due to blockade of alpha-2 adrenoceptors outside of the amygdala/pyriform region.

  10. Comparative study of the antihypertensive activity of Marrubium vulgare and of the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive rat.

    Science.gov (United States)

    El Bardai, Sanae; Lyoussi, Badiaa; Wibo, Maurice; Morel, Nicole

    2004-08-01

    Water extract of Marrubium vulgare is widely used as antihypertensive treatment in folk medicine. We have compared the effect of 10-week-long treatment with amlodipine or Marrubium water extract on systolic blood pressure (SBP), cardiovascular remodeling and vascular relaxation in spontaneously hypertensive rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium treatment had a significant antihypertrophic effect in aorta only. Relaxation to acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by amlodipine treatment. These results demonstrate that, in addition to its antihypertensive effect, Marrubium water extract improved the impaired endothelial function in SHR. PMID:15554450

  11. Comparative study of the antihypertensive activity of Marrubium vulgare and of the dihydropyridine calcium antagonist amlodipine in spontaneously hypertensive rat.

    Science.gov (United States)

    El Bardai, Sanae; Lyoussi, Badiaa; Wibo, Maurice; Morel, Nicole

    2004-08-01

    Water extract of Marrubium vulgare is widely used as antihypertensive treatment in folk medicine. We have compared the effect of 10-week-long treatment with amlodipine or Marrubium water extract on systolic blood pressure (SBP), cardiovascular remodeling and vascular relaxation in spontaneously hypertensive rats (SHR). Both treatments produced similar decrease in SBP. Amlodipine treatment reduced left ventricle, aortic and mesenteric artery weight. Marrubium treatment had a significant antihypertrophic effect in aorta only. Relaxation to acetylcholine (ACh) of mesenteric artery was improved by Marrubium but not by amlodipine treatment. These results demonstrate that, in addition to its antihypertensive effect, Marrubium water extract improved the impaired endothelial function in SHR.

  12. Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects.

    Science.gov (United States)

    Kabanov, D S; Serov, D A; Zubova, S V; Grachev, S V; Prokhorenko, I R

    2016-03-01

    The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.

  13. Releasing effects in flame photometry: Determination of calcium

    Science.gov (United States)

    Dinnin, J.I.

    1960-01-01

    Strontium, lanthanum, neodymium, samarium, and yttrium completely release the flame emission of calcium from the depressive effects of sulfate, phosphate, and aluminate. Magnesium, beryllium, barium, and scandium release most of the calcium emission. These cations, when present in high concentration, preferentially form compounds with the depressing anions when the solution is evaporated rapidly in the flame. The mechanism of the interference and releasing effects is explained on the basis of the chemical equilibria in the evaporating droplets of solution and is shown to depend upon the nature of the compounds present in the aqueous phase of the solution. The need for background correction techniques is stressed. The releasing effect is used in the determination of calcium in silicate rocks without the need for separations.

  14. Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake

    DEFF Research Database (Denmark)

    Lorenzen, J.K.; Nielsen, S.; Holst, J.J.;

    2007-01-01

    Background: High calcium intake has been shown to increase fecal fat excretion. Objective: Our aim was to examine whether a high calcium intake from dairy products or from supplements affects postprandial fat metabolism and appetite through fat malabsorption. Design: Four different isocaloric meals...... were tested in 18 subjects according to a randomized crossover design. The test meals contained high (HC meal: 172 mg/MJ), medium (MC meal: 84 mg/MJ), or low (LC meal: 15 mg/MJ) amounts of calcium from dairy products or a high amount of calcium given as a calcium carbonate supplement (Suppl meal: 183...... and approximate to 15% lower after the MC meal (P = 0.0495) and approximate to 17% lower after the HC meal (P = 0.02) than after the Suppl meal. No consistent effects of calcium on appetite sensation, or on energy intake at the subsequent meal, or on the postprandial responses of cholecystokinin, glucagon...

  15. Effects of dietary clinoptilolite and calcium levels on uric acid and calcium blood concentrations and bone quality of commercial layers

    Directory of Open Access Journals (Sweden)

    DA Berto

    2013-06-01

    Full Text Available The objective of the present study was to evaluate the effect of clinoptilolite and calcium levels on uric acid and calcium blood profile and bone quality of commercial layers. A total of 576 birds were distributed according to a completely randomized experimental design in a 3x4 factorial arrangement (calcium levels of 2.5, 3.1, or 3.7% and clinoptilolite levels of 0.0, 0.15, 0.25, or 0.50%, into 12 treatments with six replicates of eight birds per cage (experimental unit. The experimental period was 112 days. The experimental diets were based on corn and soybean meal. Results were submitted to analysis of variance and means were compared by the test of Tukey at 5% significance level using SISVAR statistical package. Blood uric acid was significantly influenced by the interaction of the evaluated factors. Clinoptilolite levels significantly increased blood calcium levels. There was no effect of dietary calcium levels on any of the evaluated characteristics. It was concluded that feeding layers with up to 0.50% clinoptilolite does not benefit blood uric acid and calcium concentrations and does not affect their bone quality. When layers at the end of the first laying cycle are fed ad libitum and present 119.50g/hen/day average feed intake, 3.1% dietary calcium promotes 3.7g/hen/day calcium intake, which is sufficient to maintain adequate calcium blood levels and bone quality.

  16. The effect of purging on sexually selected traits through antagonistic pleiotropy with survival

    OpenAIRE

    Bolstad, Geir H.; Pélabon, Christophe; Larsen, Line-K; Fleming, Ian A; Viken, Åslaug; Rosenqvist, Gunilla

    2012-01-01

    Sexually selected traits are expected to evolve to a point where their positive effect on reproductive success is counterbalanced by their negative effect on survival. At the genetic level, such a trade-off implies antagonistic pleiotropy between survival and the expression of sexually selected traits. Yet, the consequences of such a genetic architecture have been largely overlooked in studies examining how inbreeding influences sexually selected traits. These studies have solely interpreted ...

  17. ANTAGONISTIC EFFECT OF EDIBLE MUSHROOM EXTRACT ON CANDIDA ALBICANS GROWTH

    Directory of Open Access Journals (Sweden)

    Paccola Edneia A. de Souza

    2001-01-01

    Full Text Available Five species of edible mushrooms, Lentinula edodes, Pleurotus ostreatus, Pholiota nameko, Macrolepiota bonaerensis and Agaricus blazei, were tested for their potential to inhibit the in vitro growth of the pathogenic yeast Candida albicans. Only L. edodes had a fungistatic effect on this human pathogen. The inhibitory compound was produced intra and extracellularly in submersed L. edodes culture, and was also present in fresh and dehydrated mushroom basidiocarps. The fungistatic compound was heat sensitive and lost activity after 72 hours.

  18. Antagonistic effects of soybean viruses on soybean aphid performance.

    Science.gov (United States)

    Donaldson, Jack R; Gratton, Claudio

    2007-08-01

    Although there is long-standing recognition that pest complexes require different management approaches than individual pests, relatively little research has explored how pests interact. In particular, little is known of how herbivorous insects and plant pathogens interact when sharing the same host plant. The soybean aphid, Aphis glycines Mastumura, a recently introduced pest of soybean in the upper midwestern United States, and a complex of plant viruses vectored to soybean by insects have become a major concern for growers in the region. Given the abundance of soybean aphid and the increase in virus incidence in recent years, soybean aphids often use soybean infected by plant viral pathogens. We tested the hypothesis that soybean aphid performance is affected by virus infection of soybean plants. We conducted a series of field and laboratory experiments that examined how infection of soybeans with the common plant viruses, alfalfa mosaic, soybean mosaic, and bean pod mottle viruses, influenced soybean aphid performance. Soybean plants (in the field and laboratory) were hand inoculated with individual viruses, and aphids were allowed to colonize plants naturally in field experiments or added to the plants in clip-cages or within mesh bags in laboratory assays. In the field, aphid density on uninfected control soybean plants was nearly double that on infected plants. In laboratory assays, aphid population growth rates were on average 20% lower for aphids on virus infected compared with uninfected plants. Life table analyses showed that increased mortality on virus-infected plants likely explain differences in aphid population growth. Although there was some heterogeneity in the significance of treatment effects among different experiments, when independent experiments are taken together, there is on average an overall negative effect of these viruses on soybean aphids. PMID:17716484

  19. Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators

    OpenAIRE

    Gotter, Anthony L.; Garson, Susan L.; Stevens, Joanne; Munden, Regina L; Fox, Steven V.; Tannenbaum, Pamela L.; Yao, Lihang; Kuduk, Scott D.; McDonald, Terrence; Uslaner, Jason M.; Tye, Spencer J.; Coleman, Paul J.; Winrow, Christopher J; Renger, John J.

    2014-01-01

    Background The current standard of care for insomnia includes gamma-aminobutyric acid receptor A (GABAA) activators, which promote sleep as well as general central nervous system depression. Dual orexin receptor antagonists (DORAs) represent an alternative mechanism for insomnia treatment that induces somnolence by blocking the wake-promoting effects of orexin neuropeptides. The current study compares the role and interdependence of these two mechanisms on their ability to influence sleep arc...

  20. Effect of gonadal hormones on hypophagic property of opioid antagonist Naloxone

    OpenAIRE

    Gargate Ashwini R, Kulkarni Dushant V

    2014-01-01

    Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these Gonadal hormones interact with Opioid ...

  1. Antimicrobial effectiveness of different preparations of calcium hydroxide

    Directory of Open Access Journals (Sweden)

    Anshul Gangwar

    2011-01-01

    Results and Conclusions: It was seen that calcium hydroxide and CMCP combination showed the maximum zone of inhibition, and maximum inhibitory effect was seen at 24 hours. The bacteria most susceptible was found to be S. aureus and the least susceptible was E. faecalis. Further clinical studies are required to substantiate these results.

  2. Effects of N-methyl-D-aspartate antagonists on different measures of motion sickness in cats.

    Science.gov (United States)

    Lucot, J B

    1998-11-15

    Because N-methyl-D-aspartate (NMDA) antagonists prevent cisplatin-induced emesis and NMDA receptors are in both emetic pathways and structures associated with the final common pathway for vomiting, they have the potential to be broad-spectrum antiemetics. This was evaluated by determining their effects on motion sickness in cats. The measures included the number vomiting, the number of symptom points, which reflect activity early in the final common path and the duration of the retch/vomit sequence, which reflects activity late in the path. Dextrorphan, ketamine and dextromethorphan decreased the number vomiting with the same rank order of potency as at NMDA receptors. Additional studies with 1,3-dio-tolylguaninidine (DTG) and haloperidol ruled out a role for sigma receptors. The NMDA antagonists produced a nonsignificant dose-dependent decrease in symptoms and had no effects on the duration of vomiting. They also produced motor abnormalities at the highest doses. The competitive antagonist LY 233053 also decreased the number vomiting without altering the duration. It produced a nonsignificant non-dose-dependent decrease in symptoms and had no effects on gross motor output. The results are consistent with a broad spectrum of antiemetic efficacy with at least a part of its action in the early to middle portions of the final common pathway for vomiting. Additional actions on the vestibular nuclei are possible. PMID:10052568

  3. Antagonistic and synergistic effects of light irradiation on the effects of copper on Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Highlights: • Light intensity and spectral composition affect Cu uptake and effects to C. reinhardtii. • High light (HL) reduced Cu effect on growth inhibition, oxidative stress and damage. • HL in combination with Cu up-regulated genes involved in the antioxidant responses. • HL with increased UVB radiation exacerbated Cu uptake and Cu-induced toxic effects. - Abstract: The present study showed the important role of light intensity and spectral composition on Cu uptake and effects on green alga Chlamydomonas reinhardtii. High-intenisty light (HL) increased cellular Cu concentrations, but mitigated the Cu-induced decrease in chlorophyll fluorescence, oxidative stress and lipid peroxidation at high Cu concentrations, indicating that Cu and HL interact in an antagonistic manner. HL up-regulated the transcription of genes involved in the antioxidant response in C. reinhardtii and thus reduced the oxidative stress upon exposure to Cu and HL. Combined exposure to Cu and UVBR resulted in an increase of cellular Cu contents and caused severe oxidative damage to the cells. The observed effects were higher than the sum of the effects corresponding to exposure to UVBR or Cu alone suggesting a synergistic interaction

  4. Antagonistic and synergistic effects of light irradiation on the effects of copper on Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Cheloni, Giulia; Cosio, Claudia; Slaveykova, Vera I., E-mail: vera.slaveykova@unige.ch

    2014-10-15

    Highlights: • Light intensity and spectral composition affect Cu uptake and effects to C. reinhardtii. • High light (HL) reduced Cu effect on growth inhibition, oxidative stress and damage. • HL in combination with Cu up-regulated genes involved in the antioxidant responses. • HL with increased UVB radiation exacerbated Cu uptake and Cu-induced toxic effects. - Abstract: The present study showed the important role of light intensity and spectral composition on Cu uptake and effects on green alga Chlamydomonas reinhardtii. High-intenisty light (HL) increased cellular Cu concentrations, but mitigated the Cu-induced decrease in chlorophyll fluorescence, oxidative stress and lipid peroxidation at high Cu concentrations, indicating that Cu and HL interact in an antagonistic manner. HL up-regulated the transcription of genes involved in the antioxidant response in C. reinhardtii and thus reduced the oxidative stress upon exposure to Cu and HL. Combined exposure to Cu and UVBR resulted in an increase of cellular Cu contents and caused severe oxidative damage to the cells. The observed effects were higher than the sum of the effects corresponding to exposure to UVBR or Cu alone suggesting a synergistic interaction.

  5. Zeolite A effect on calcium homeostasis in growing goats.

    Science.gov (United States)

    Schwaller, D; Wilkens, M R; Liesegang, A

    2016-04-01

    The purpose of this study was to investigate the influence of 2 different concentrations of zeolite A on calcium homeostasis. Seventeen growing goats were divided into 3 groups. Whereas the control group (5 animals) received no supplementation, 2 treatment groups were supplemented with zeolite A at either 1.2 (6 animals) or 1.6 g/kg BW (6 animals), respectively. Blood and urine samples were continually drawn and bone mineral density was measured weekly by peripheral quantitative computed tomography. After 3 wks, the animals were slaughtered and samples were taken from the rumen, duodenum, and kidneys. Plasma concentrations of phosphate ( Ussing chamber technique and quantification of RNA and protein expression of genes known to be involved in active calcium absorption did not reveal any stimulating effect of zeolite. Plasma calcium concentrations were not altered, probably because of the sufficient dietary calcium supply. However due to the effects of zeolite on 1,25 dihydroxycholecalciferol, bone metabolism and serum concentrations of phosphate and magenesium shown in the present study, potential negative long-termin effects on the animals should be considered whenever rations with zeolite are designed. PMID:27136016

  6. Effect of lowering dietary calcium intake on fractional whole body calcium retention

    Energy Technology Data Exchange (ETDEWEB)

    Dawson-Hughes, B.; Stern, D.T.; Shipp, C.C.; Rasmussen, H.M.

    1988-07-01

    Although fractional calcium absorption is known to vary inversely with calcium intake, the extent and timing of individual hormonal and calcium absorption responses to altered calcium intake have not been defined. We measured fractional whole body retention of orally ingested /sup 47/Ca, an index of calcium absorption, in nine normal women after they had eaten a 2000-mg calcium diet for 8 weeks and a 300-mg calcium diet for 1, 2, 4, and 8 weeks. After the diet change, serum intact PTH (32.2% increase; P = 0.005), serum 1,25-dihydroxyvitamin D (1,25-(OH)2D; 43.8% increase; P = 0.003), and fractional whole body calcium retention (42.8% increase; P = 0.004) increased within 1 week. Although the PTH and calcium retention responses remained fairly constant throughout the low calcium intake period, serum 1,25-(OH)2D concentrations declined toward baseline after week 1. Thus, the late increase in calcium retention may have resulted from calcium absorption that was independent of 1,25-(OH)2D stimulation.

  7. Effect of humic substances on the precipitation of calcium phosphate

    Institute of Scientific and Technical Information of China (English)

    SONG Yong-hui; Hermann H. HAHN; Erhard HOFFMANN; Peter G. WEIDLER

    2006-01-01

    For phosphorus (P) recovery from wastewater, the effect of humic substances (HS) on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate (as P) and 20 mg/L HS (as dissolved organic carbon, DOC) at a constant pH value in the range of 8.0-10.0. The concentration variations of phosphate, calcium (Ca) and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction (XRD) and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH ≥9.0,the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations ≤ 3.5 mg/L, and at pH ≥ 9.0 and HS concentrations ≤ 10 mg/L, the final precipitates were proved to be hydroxyapatite (HAP) by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate.

  8. The Central Reinforcing Properties of Ethanol Are Mediated by Endogenous Opioid Systems: Effects of Mu and Kappa Opioid Antagonists.

    Directory of Open Access Journals (Sweden)

    Norman E. Spear

    2009-09-01

    Full Text Available Endogenous opioid systems are implicated in the reinforcing effects of ethanol and may play a substantial role in modulating the central reinforcing effects of ethanol early in ontogeny. This possibility was explored in the present study through the use of an olfactory conditioning paradigm with centrally administered ethanol serving as an unconditioned stimulus (US. In Experiment 1, newborn rat pups were treated with either a selective mu antagonist CTOP or kappa selective antagonist nor-BNI prior to olfactory conditioning. Experiment 2 tested the effectiveness of an alternative, shorter-duration kappa opioid antagonist GNTI in altering ethanol reinforcement. Experiment 3 investigated whether the effectiveness of pharmacological blockade of opioid receptors was due to the disruption of learning per se using an olfactory aversive conditioning paradigm with intraoral quinine serving as a US. Central administration of either mu or kappa opioid antagonists prior to conditioning disrupted the reinforcing effects of ethanol in newborn rats. The kappa opioid antagonist GNTI was as effective as nor-BNI. These effects of opioid antagonists on ethanol reinforcement are unlikely to be due to a disruption of all types of conditioning, since CTOP did not affect aversive reinforcement to intraoral infusions of quinine. The present results support the hypothesis that in newborn rats, the reinforcing properties of ethanol are mediated by the endogenous activity at mu and kappa opioid receptors.

  9. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander;

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  10. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander;

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with ß-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with ß-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  11. Calcium intake and prostate cancer among African Americans: effect modification by vitamin D receptor calcium absorption genotype.

    Science.gov (United States)

    Rowland, Glovioell W; Schwartz, Gary G; John, Esther M; Ingles, Sue Ann

    2012-01-01

    High dietary intake of calcium has been classified as a probable cause of prostate cancer, although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African-American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African-American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared with men in the lowest quartile of calcium intake, men in the highest quartile had an approximately twofold increased risk of localized and advanced prostate cancer (odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR = 0.41, 95% CI = 0.19, 0.90). The gene-calcium interaction was statistically significant (p = 0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared with men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium.

  12. Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation

    DEFF Research Database (Denmark)

    Sampson, Anthony P; Pizzichini, Emilio; Bisgaard, Hans

    2003-01-01

    treatment and management, and investigation of the relation between CysLTs and airway inflammation in asthma. Nitric oxide is also a surrogate marker of asthma and reflects airway inflammation. The anti-inflammatory effects of the leukotriene receptor antagonists and the markers of their activity continue......The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct...

  13. The salutary effect of dietary calcium on bone mass in a rat model of simulated weightlessness

    Science.gov (United States)

    Bikle, D. D.; Globus, R.; Halloran, B. P.; Morey-Holton, E.

    1985-01-01

    Whether supplementation of dietary calcium reduces the differences in bone mass of unweighed limbs and normally weighted limbs, and whether parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) respond differently to dietary calcium in unweighted animals in comparison with pair-fed controls was studied. The hind limbs of rats were unweighted by a tail suspension method and diets containing 0.1% to 2.4% calcium. After 2 weeks serum calcium, phosphorus, PTH and 1,25(OH)2D intestinal calcium transport were determined and bone mass, ash weight, and calcium in the tibia, L-1 vertebra, and humerus were measured. No significant differences in body weights were observed among the various groups. Suspended rats maintained constant levels of serum calcium and phosphate over the wide range of dietary calcium. Serum PTH and 1,25(OH)2D and intestinal calcium transport fell as dietary calcium was increased. Bone calcium in the tibia and vertebra from suspended rats remained less than that from pair-fed control. It is suggested that although no striking difference between suspended and control animals was observed in response to dieteary calcium, increasing dietary calcium may reduce the negative impact of unloading on the calcium content of the unweighted bones. The salutary effect of high dietary calcium appears to be due to inhibition of bone resorption rather than to stimulation of bone formation.

  14. Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients

    Directory of Open Access Journals (Sweden)

    Nishiura J.L.

    2002-01-01

    Full Text Available Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 ± 10 years old, whose 4-day dietary records revealed a regular low calcium intake (<=500 mg/day, received an oral calcium load (1 g/day for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15, diet-dependent hypercalciuric (DDHC, N = 9 or diet-independent hypercalciuric (DIHC, N = 26. On regular diet, mean oxaluria was 30 ± 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 ± 12 vs 26 ± 7 and 27 ± 18 vs 32 ± 15 mg/24 h, respectively, P<0.05 but not in DDHC patients (22 ± 10 vs 23 ± 5 mg/24 h. The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.

  15. Antagonistic Effects of Sodium Butyrate and N-(4-Hydroxyphenyl-retinamide on Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Rainer Kuefer

    2007-03-01

    Full Text Available Butyrates and retinoids are promising antineoplastic agents. Here we analyzed effects of sodium butyrate and N-(4-hydroxyphenyl-retinamide (4-HPR on prostate cancer cells as monotherapy or in combination in vitro and in vivo. Sodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered together antagonize effects of each other. For the in vivo studies, a water-soluble complex (4-HPR with a cyclodextrin was created. A single dose of sodium butyrate and 4-HPR showed a peak level in chicken plasma within 30 minutes. Both compounds induced inhibition of proliferation and apoptosis in xenografts of the chicken chorioallantoic membrane. Analysis of the cytotoxic effects of the drugs used in combination demonstrated an antagonistic effect on inhibition of proliferation and on induction of apoptosis. Prolonged jun N-terminal kinase phosphorylation induced by sodium butyrate and 4-HPR was strongly attenuated when both compounds were used in combination. Both compounds induced inhibition of NF-κ,B. This effect was strongly antagonized in LNCaP cells when the compounds were used in combination. These results indicate that combinational therapies have to be carefully investigated due to potential antagonistic effects in the clinical setting despite promising results of a monotherapy.

  16. Differential effect of glucocorticoid receptor antagonists on glucocorticoid receptor nuclear translocation and DNA binding

    Science.gov (United States)

    Spiga, Francesca; Knight, David M; Droste, Susanne K; Conway-Campbell, Becky; Kershaw, Yvonne; MacSweeney, Cliona P; Thomson, Fiona J; Craighead, Mark; Peeters, Bernard WMM; Lightman, Stafford L

    2016-01-01

    The effects of RU486 and S-P, a more selective glucocorticoid receptor antagonist from Schering-Plough, were investigated on glucocorticoid receptor nuclear translocation and DNA binding. In the in vitro study, AtT20 cells were treated with vehicle or with RU486, S-P or corticosterone (3–300 nM) or co-treated with vehicle or glucocorticoid receptor antagonists (3–300 nM) and 30 nM corticosterone. Both glucocorticoid receptor antagonists induced glucocorticoid receptor nuclear translocation but only RU486 induced DNA binding. RU486 potentiated the effect of corticosterone on glucocorticoid receptor nuclear translocation and DNA binding, S-P inhibited corticosterone-induced glucocorticoid receptor nuclear translocation, but not glucocorticoid receptor-DNA binding. In the in vivo study, adrenalectomized rats were treated with vehicle, RU486 (20 mg/kg) and S-P (50 mg/kg) alone or in combination with corticosterone (3 mg/kg). RU486 induced glucocorticoid receptor nuclear translocation in the pituitary, hippocampus and prefrontal cortex and glucocorticoid receptor-DNA binding in the hippocampus, whereas no effect of S-P on glucocorticoid receptor nuclear translocation or DNA binding was observed in any of the areas analysed. These findings reveal differential effects of RU486 and S-P on areas involved in regulation of hypothalamic–pituitary–adrenal axis activity in vivo and they are important in light of the potential use of this class of compounds in the treatment of disorders associated with hyperactivity of the hypothalamic–pituitary–adrenal axis. PMID:20093322

  17. Pharmacodynamic responses to combined treatment regimens with the calcium sensing receptor antagonist JTT-305/MK-5442 and alendronate in osteopenic ovariectomized rats.

    Science.gov (United States)

    Fisher, John E; Scott, Kevin; Wei, Nan; Zhao, Jing Z; Cusick, Tara; Tijerina, Monica; Karanam, Bindhu; Duong, Le; Glantschnig, Helmut

    2012-06-01

    Parathyroid hormone (PTH) is the anabolic standard of care for patients with severe osteoporosis. The CaSR allosteric antagonist JTT-305/MK-5442, a PTH secretagogue, could offer an oral osteoanabolic treatment alternative for postmenopausal women with osteoporosis. Here we disclose the pharmacokinetic profile of JTT-305/MK-5442 and its activity on bone remodeling in ovariectomized (OVX) osteopenic rats. Daily treatments (0.3 to 2.4 mg/kg/d) for 12 weeks resulted in plateaued BMD increases (3.8 to 5.3%) at axial and appendicular skeletal sites. However, treatment effects were not statistically significant, in agreement with effects seen in animals treated with low dose PTH (1-84) (5 μg/kg/d). In a consecutive study we tested JTT-305/MK-5442 effects on bone formation in OVX-rats challenged with combined alendronate (ALN) treatment paradigms. At 7 month, JTT-305/MK-5442 treatment significantly increased BMD in lumbar vertebrae (LV), while no change in BMD was observed in femora or tibiae. ALN add-on co-treatment produced incremental increases in LV, distal femur (DF) and proximal tibia (PT) BMD over the respective ALN control. Histological analyses confirmed modest increases in mineralized surface (MS/BS) and bone formation rate (30.5±1.9%) on trabecular surfaces by JTT-305/MK-5442. As expected, ALN administration profoundly reduced bone formation, however, JTT-305/MK-5442 significantly stimulated MS/BS and BFR in ALN treated groups. In summary, JTT-305/MK-5442 acts as a PTH secretagogue in the osteopenic OVX-rat, eliciting consistent, though modest effects on remediation of BMD due to estrogen depletion. Induction of bone formation by JTT-305/MK-5442 at trabecular bone surfaces appears to be resilient to ALN-mediated suppression of bone formation. This study provides for the first time, a mechanistic evaluation of combination treatment of a PTH secretagogue with ALN.

  18. Effects of selenium, calcium and calcium ionophore on human oocytes in vitro maturation in a chemically defined medium

    OpenAIRE

    Hessam Roustaei; Mohammad Hasan Fallahian; Fatemeh Peyghambari; Raheleh Aram; Mohammad Ali Sabbaghi; Elham Saboori; Mehri Makki; Abbas Ahmadi

    2012-01-01

    Background: In vitro maturation (IVM) of human oocytes is an emerging procedure quickly incorporated into the world of assisted reproductive technologies. As an effective method of in vitro maturation, several studies have reported the critical role of differentions on activating the complex process involved in both gamete maturation and fertilization. Objective: In this study, we supplemented a chemically defined medium with different combinations of selenium, calcium and calcium ionophore c...

  19. A quantitative model for presynaptic free calcium dynamics during the induction of long-term effects

    CERN Document Server

    Erler, F; Soff, G; Erler, Frido; Meyer-Hermann, Michael; Soff, Gerhard

    2002-01-01

    The presynaptic free calcium dynamics of neurons due to various stimulation protocols is investigated in a mathematical model. Especially, connections between free calcium dynamics and the induction of synaptic long-term effects are considered. The model includes calcium influx through voltage-directed calcium channels, calcium buffering by endogenous and exogenous buffers as well as calcium efflux through ATP-driven plasma membrane calcium pumps and sodium/calcium exchangers. A classification of parameters into universal (widely independent of neuron types) and specific ones (depending on neuron type and experimental setup) allows the applications of the model to different classes of neurons and experiments. This is demonstrated for single boutons of pyramidal neurons of the rat neocortex. The model parameters are determined using corresponding fluorescence measurements. The model enables us to reconstruct the free calcium dynamics in neurons as it would have been without fluorescence indicators starting fro...

  20. No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

    DEFF Research Database (Denmark)

    Estrup, T M; Paulson, O B; Strandgaard, S

    2001-01-01

    Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral...... circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT2-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control...

  1. Effect of albumin and free calcium concentrations on calcium binding in vitro.

    OpenAIRE

    Besarab, A; DeGuzman, A; Swanson, J W

    1981-01-01

    In vivo equilibrium dialysis studies were performed to define further the characteristics of calcium binding to bovine albumin. The concentration range for albumin (1 to 9 g/dl) as well as ultrafilterable calcium (0.5 to 2.5 mM) studied encompassed those that might be ordinarily encountered in most clinical situations. Major differences in the regressions of total calcium on ultrafilterable calcium occurred at albumin concentrations of 1, 2, and 9 g/dl but only small differences at albumin co...

  2. Effect of Calcium on the Vanadium Extraction from High Calcium Type Stone Coal

    Institute of Scientific and Technical Information of China (English)

    BAO Shenxu; LIANG Liang; ZHANG Yimin; HAN Shihua; HU Yangjia

    2015-01-01

    The high calcium type stone coal from Hubei province was leached by water and dilute acid separately after being roasted with different dosage of NaCl. The water leaching rate of vanadium (WLRV) was low and only 26.8%of vanadium can be leached by water when 4%NaCl was added, but the acid leaching rate of vanadium (ALRV) was relatively high. Calcium in the high calcium type stone coal is greatly superfluous relative to vanadium, hence, the calcium reacts with vanadium to form Ca(VO3)2, Ca2V2O7 and Ca3(VO4)2 orderly during the stone coal roasting process and high temperature is beneficial to the reactions between calcium and vanadium, which was validated by simulated reactions between pure calcium carbonate and vanadium pentoxide. These calcium vanadates are all water insoluble but acid soluble and this causes the low WLRV and relatively high ALRV. After calcium removal by HCl, the WLRV is highly enhanced and reaches about 50%when only 2%NaCl was added. If the HCl content is too high, the stone coal is easily sintered and the formed glass structure can enwrap vanadium, which leads the WLRV to decline. Single water leaching process is not appropriate to extract vanadium from high calcium type stone coal.

  3. Effect of Strength Enhancement of Soil Treated with Environment-Friendly Calcium Carbonate Powder

    OpenAIRE

    Kyungho Park; Sangju Jun; Daehyeon Kim

    2014-01-01

    This study aims to investigate the effects of the strength improvement of soft ground (sand) by producing calcium carbonate powder through microbial reactions. To analyze the cementation effect of calcium carbonate produced through microbial reaction for different weight ratios, four different types of specimens (untreated, calcium carbonate, cement, and calcium carbonate + cement) with different weight ratios (2%, 4%, 6%, and 8%) were produced and cured for a period of 3 days, 7 days, 14 day...

  4. Two short-acting kappa opioid receptor antagonists (zyklophin and LY2444296) exhibited different behavioral effects from the long-acting antagonist norbinaltorphimine in mouse anxiety tests.

    Science.gov (United States)

    Huang, Peng; Yakovleva, Tatyana; Aldrich, Jane V; Tunis, Julia; Parry, Christopher; Liu-Chen, Lee-Yuan

    2016-02-26

    Prototypical long-acting kappa opioid receptor (KOPR) antagonists [e.g., norbinaltorphimine (norBNI)] have been reported to exert anxiolytic-like effects in several commonly used anxiety tests in rodents including the novelty-induced hypophagia (NIH) and elevated plus maze (EPM) tests. It remains unknown if the short-acting KOPR antagonists (e.g., zyklophin and LY2444296) have similar effects. In this study effects of zyklophin and LY2444296 (s.c.) were investigated in the NIH and EPM tests in mice 1h post-injection and compared with norBNI (i.p.) 48h post-administration. In the NIH test, zyklophin at 3 and 1mg/kg, but not 0.3mg/kg, or LY2444296 at 30mg/kg decreased the latency of palatable food consumption in novel cages, but had no effect in training cages, similar to norBNI (10mg/kg). Zyklophin at 3 or 1mg/kg increased or had a trend of increasing the amount of palatable food consumption in novel cages, with no effects in training cages, further indicating its anxiolytic-like effect, but norBNI (10mg/kg) and LY2444296 (30mg/kg) did not. In the EPM test, norBNI (10mg/kg) increased open arm time and % open arm entries or time, but zyklophin at all three doses and LY2444296 (30mg/kg) had no effects. In addition, zyklophin at 3mg/kg increased numbers of close and total arm entries on EPM, suggesting increased activity; however, norBNI and LY2444296 had no effects on close and total arm entries. Thus, all three KOPR antagonists had anxiolytic-like effects in the NIH test. However, only the long-acting one (norBNI), but not the short-acting ones (zyklophin and LY2444296), demonstrated anti-anxiety like effects in the EPM test. It remains to be investigated if the differences are due to the differences in their durations of action and/or pharmacodynamic properties.

  5. The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats

    Directory of Open Access Journals (Sweden)

    Colin N. Haile

    2012-11-01

    Full Text Available Medications that target norepinephrine (NE neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX, a longer-acting α1 antagonist blocked cocaine’s subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6–8 were administered saline, cocaine (COC, 10 mg/kg or DOX (0.3 or 1.0 mg/kg alone or in combination for 5 consecutive days (development. Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression. COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg, but not the low dose (0.3 mg/kg of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine’s behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.

  6. Nitroester drug's effects and their antagonistic effects against morphine on human sphincter of Oddi motility

    Institute of Scientific and Technical Information of China (English)

    Shuo-Dong Wu; Zhen-Hai Zhang; Dong-Yan Li; Jun-Zhe Jin; Jing Kong; Zhong Tian; Wei Wang; Min-Fei Wang

    2005-01-01

    AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P<0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P<0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P<0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most

  7. Effect of α7 nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    International Nuclear Information System (INIS)

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  8. Antagonistic effect of Pseudomonas aeruginosa isolates from various ecological niches on Vibrio species pathogenic to crustaceans

    Institute of Scientific and Technical Information of China (English)

    Prabhakaran Priyaja; Puthumana Jayesh; Neil Scolastin Correya; Balachandran Sreelakshmi; Naduthalmuriparambil S Sudheer; Rosamma Philip; Isaac Sarogeni Bright Singh

    2014-01-01

    Objective: To abrogate pathogenic vibrios in aquaculture by testing the potential of Pseudomonas isolates from fresh water, brackish and marine environments as probiotics.Methods:Antagonistic activity of the compound against 7 Vibrio spp. was performed. Influence of salinity on the production of pyocyanin and the toxicity was done through the compound using brine shrimp lethality assay. Molecular characterization was performed to confirm that the isolates werePseudomonas aeruginosa. Results: Salinity was found to regulate the levels of pyocyanin production, with 5-10 g/L as the optimum. All Pseudomonas isolates grew at salinities ranging from 5 to 70 g/L. Isolates of marine origin produced detectable levels of pyocyanin up to 45 g/L salinity. Brackish and freshwater isolates ceased to produce pyocyanin at salinities above 30 g/L and 20 g/L, respectively. Culture supernatants of all 5 Pseudomonas isolates possessed the ability to restrict the growth of Vibrio spp. and maximum antagonistic effect on Vibrio harveyi was obtained when they were grown at salinities of 5 to 10 g/L. The marine isolate MCCB117, even when grown at a salinity of 45 g/L possessed the ability to inhibit Vibrio spp.Conclusions:Purification and structural elucidation of antagonistic compound were carried out. ideal for application in freshwater, MCCB102 and MCCB103 in brackish water and MCCB117 and The present investigation showed that Pseudomonas aeruginosa MCCB119 would be MCCB118 in marine aquaculture systems as putative probiotics in the management of vibrios.

  9. Effect of α₇ nicotinic acetylcholine receptor agonists and antagonists on motor function in mice.

    Science.gov (United States)

    Welch, Kevin D; Pfister, James A; Lima, Flavia G; Green, Benedict T; Gardner, Dale R

    2013-02-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline.

  10. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3, 25,26-dihydroxyvitamin D3, and 1,24,25-trihydroxyvitamin D3), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3, the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

  11. Suppressant effects of selective 5-HT2 antagonists on rapid eye movement sleep in rats.

    Science.gov (United States)

    Tortella, F C; Echevarria, E; Pastel, R H; Cox, B; Blackburn, T P

    1989-04-24

    The effects of the novel, highly selective serotonin-2 (5-HT2) antagonists, ICI 169,369 and ICI 170,809, on 24 h EEG sleep-wake activity were studied in the rat. Both compounds caused a dose-related increase in the latency to rapid eye movement sleep (REMS) and significantly suppressed cumulative REMS time up to 12 h postinjection. In contrast, neither drug disrupted slow-wave sleep continuity in as much as the latency to non-REMS (NREMS) and cumulative NREMS time were unchanged. However, at the highest dose tested (20 mg/kg) ICI 170,809 did produce a significant increase in total NREMS time during the second half of the sleep-awake cycle. These results demonstrate effects of selective 5-HT2 antagonists on sleep in rats which appear to be specific for REMS behavior, suggesting that the priming influence of serotonin on REMS may involve 5-HT2 receptor subtypes. The relationship between the REMS suppressant actions of these compounds and their consideration as therapeutic agents in depression is discussed.

  12. Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Sherry; Chen, Jin Ching; Hsu, Chin Wei; Chang, Walter H, E-mail: whchang@cycu.edu.t [Center for Nano Bioengineering, Chung Yuan Christian University, Chung Li 32023, Taiwan (China); Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li 32023, Taiwan (China)

    2009-09-16

    Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg{sup -1} body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

  13. Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model

    Science.gov (United States)

    Huang, Sherry; Chen, Jin Ching; Hsu, Chin Wei; Chang, Walter H.

    2009-09-01

    Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg-1 body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

  14. Effect of calcium on adsorption capacity of powdered activated carbon.

    Science.gov (United States)

    Li, Gang; Shang, Junteng; Wang, Ying; Li, Yansheng; Gao, Hong

    2013-12-01

    We investigated the effect of calcium ion on the adsorption of humic acid (HA) (as a target pollutant) by powered activated carbon. The HA adsorption isotherms at different pH and kinetics of two different solutions including HA alone and HA doped Ca(2+), were performed. It was showed that the adsorption capacity of powdered activated carbon (PAC) for HA was markedly enhanced when Ca(2+) was doped into HA. Also, HA and Ca(2+) taken as nitrate were tested on the uptake of each other respectively and it was showed that the adsorbed amounts of both of them were significantly promoted when HA and calcium co-existed. Furthermore, the adsorbed amount of HA slightly decreased with the increasing of Ca(2+) concentration, whereas the amount of calcium increased with the increasing of HA concentration, but all above the amounts without addition. Finally, the change of pH before and after adsorption process is studied. In the two different solutions including HA alone and HA doped Ca(2+), pH had a small rise, but the extent of pH of later solution was bigger. PMID:25078809

  15. Effect of mitochondrial calcium uniporter blocking on human spermatozoa.

    Science.gov (United States)

    Bravo, A; Treulen, F; Uribe, P; Boguen, R; Felmer, R; Villegas, J V

    2015-08-01

    Calcium (Ca(2+) ) regulates a number of essential processes in spermatozoa. Ca(2+) is taken up by mitochondria via the mitochondrial calcium uniporter (mCU). Oxygen-bridged dinuclear ruthenium amine complex (Ru360) has been used to study mCU because it is a potent and specific inhibitor of this channel. In bovine spermatozoa, it has been demonstrated that mitochondrial calcium uptake inhibition adversely affects the capacitation process. It has been demonstrated in human spermatozoa that mCU blocking, through Ru360, prevents apoptosis; however, the contribution of the mCU to normal human sperm function has not been studied. Therefore, the aim of this study was to evaluate the effect of mCU blocking on human sperm function. Spermatozoa obtained from apparently healthy donors were incubated with 5 and 10 μm Ru360 for 4 h at 37 °C. Viability was assessed using propidium iodide staining; motility was determined by computer-aided sperm analysis, adenosine triphosphate (ATP) levels using a luminescence-based method, mitochondrial membrane potential (ΔΨm) using JC-1 staining and reactive oxygen species (ROS) production using dihydroethidium dye. Our results show that mCU blocking significantly reduced total sperm motility and ATP levels without affecting sperm viability, ΔΨm and ROS production. In conclusion, mCU contributes to the maintenance of sperm motility and ATP levels in human spermatozoa.

  16. Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway.

    Science.gov (United States)

    Lee, Eunkyung; Choi, So-Young; Yang, Jae-Ho; Lee, Youn Ju

    2016-07-01

    Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway. PMID:27382356

  17. Effect of GnRH antagonist on follicular development and uterine biophysical profile in controlled ovarian stimulation

    Directory of Open Access Journals (Sweden)

    Bhawana Tiwary

    2015-02-01

    Full Text Available Background: Objective of current study was to assess the effect of GnRH antagonist on follicular development, premature luteinization, uterine biophysical profile and pregnancy rate in controlled ovarian stimulation with clomiphene and gonadotropins for intrauterine insemination in women with unexplained infertility. Methods: Randomised controlled trial. Minimal stimulation protocol with or without GnRH antagonist was compared. Setting: Infertility clinic, PGIMER, Chandigarh. Patients: Couples with unexplained infertility, age of female partner between 20-39 years. Intervention: GnRH antagonist 0.25 mg since follicle size 14 mm till hCG administration. Main outcome measures: Follicle characteristics, premature luteinisation, uterine biophysical profile and pregnancy rate. Results: The mean number of follicles recruited in group A was 2.32 +/- 1.01 while that in group B (receiving GnRH antagonist it was 4.10 +/- 1.69. Statistically significant increase in total biophysical profile score was observed in periovulatory phase in the antagonist group. 40% women in group A had premature luteinization whereas only 4% women in group B suffered from premature luteinization. 20% women who received GnRH antagonist conceived against only 6% in group A, this difference however was not statistically significant Conclusions: GnRH antagonist has a role in increasing the number of follicles recruited. Furthermore, GnRH antagonist can improve the total uterine biophysical profile score by improving the endometrial thickness, endometrial pattern, blood flow and decreasing the impedance to the blood flow in uterine artery. The drug can potentially help in improving pregnancy rates by decreasing the rate of premature luteinisation. [Int J Reprod Contracept Obstet Gynecol 2015; 4(1.000: 157-163

  18. Effect of calcium chloride and calcium lactate on quality and shelf-life of fresh-cut guava slices

    International Nuclear Information System (INIS)

    Present study was conducted to investigate the effectiveness of chemical treatments at low temperature on the quality of fresh-cut guava slices during 2011-12. Uniform sized guava slices were made free from seeds and treated with calcium chloride and calcium lactate with concentration 0.9%, 1.8%, 2.7% or 3.6%. After packing in plastic boxes, all treated samples were stored at 5 degree C + 2 degree C in a refrigerator for 24 days with 6 day interval between different removals. The results obtained from physico-chemical analysis showed decrease in firmness (111.67-12.67gf) and increase in browning (1.19-1.93nm) of guava slices compared to control with the passage of storage interval. Moreover, scores in taste (7.33-1.00), flavour (7.33-1.00), colour (7.50-1.00) and texture (7.67-1.00) of guava slices was also decreased with respect to interaction of treatments and storage period. Calcium chloride at the rate 2.7% showed significantly higher stability than other concentrations of calcium chloride and calcium lactate in delaying firmness and browning of fresh-cut guava slices along with maintaining their organoleptic properties for longer storage period. However, calcium chloride imparted undesirable bitterness to fresh-cut guava slices at the concentration of 3.6%. Based on the overall quality performance, 2.7% calcium chloride and 3.6% calcium lactate exhibited better results than other concentrations and control with storage life of 8 days at 5 degree C + 2 degree C. (author)

  19. Effect of calcium and vitamin D supplementation on serum calcium level in children with idiopathic nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Vaya Dasitania

    2014-05-01

    Full Text Available Background Patients with idiopathic nephrotic syndrome (NS may develop hypocalcemia caused by low levels of albumin and vitamin D-binding protein, which subsequently decreases calcium absorption in the intestine. Hypocalcemia may result in neuromuscular manifestations, such as Chvostek’s and Trosseau’s signs. Objectives To evaluate the effect of calcium and vitamin D supplementation on hypocalcemia and its clinical manifestations in idiopathic NS children. Methods A randomized, single-blind, controlled trial was performed in idiopathic NS patients aged 1−14 years. Subjects were divided into treatment and placebo groups. Subjects in the treatment group received 800 mg elemental calcium and 400 IU vitamin D supplementation, while they in control group received placebo syrup, both for 8 weeks. Serum calcium and manifestations of hypocalcemia were examined before and after supplementation. Results Thirty subjects completed the study (15 in each group. Seventeen subjects experienced hypocalcemia. Chvostek’s and Trosseau’s signs were observed in 6 subjects in the treatment group and 2 subjects in the placebo group (P= 0.427. After 8 weeks of intervention, Chvostek’s and Trosseau’s signs disappeared in both groups, and calcium levels were significantly increased in both groups compared to the levels before intervention. However, there was no significant difference in serum calcium levels after 8 weeks between the treatment and placebo groups (P =0.707. Conclusion Normalization of serum calcium levels and improved clinical manifestations of hypocalcemia occur both in NS patients who receive calcium and vitamin D supplementation and those who do not.

  20. Characterization of mechanisms involved in presynaptic inhibition of sympathetic pressor effects induced by some 5-HT1 receptor antagonists.

    Science.gov (United States)

    Fernández, M M; Calama, E; Morán, A; Martín, M L; San Román, L

    2000-01-01

    1. In a previous study, we showed that the presynaptic inhibitory action of 5-hydroxytryptamine receptor agonists on sympathetic pressor effects obtained in the pithed rats were mainly mediated by activation of 5-HT1A and 5-HT1D receptor subtypes. At the time, we observed that some 5-HT1 receptors antagonists - WAY 100,635 and NAN-190 (both 5-HT1A receptor antagonists), methiothepin (a 5-HT1,2,5,6,7 receptor antagonist) and spiperone (a 5-HT1,2 receptor antagonist) - reduced per se the pressor effects obtained by electrical stimulation. The aim of the present work was to investigate the mechanism participating in this inhibitory effect. 2. The inhibition induced by WAY 100,635 (1000 microg kg-1, i.v.) was blocked after i.v. treatment with idazoxan, an alpha2-adrenoceptor antagonist (300 and 1000 microg kg-1) and was not modified after i.v. treatment with propranolol, a beta-adrenoceptor antagonist (1000 microg kg-1) and sulpiride, a D2 receptor antagonist (1000 microg kg-1). The inhibition induced by spiperone (500 microg kg-1 i.v.) was significantly blocked by sulpiride (1000 microg kg-1) and was not modified by idazoxan or propranolol. 3. Sulpiride (1000 microg kg-1) partially blocked the inhibition induced by methiothepin (50 microg kg-1 i.v.). Only pretreatment with idazoxan (300 microg kg-1) modified the inhibition induced by NAN-190 (100 microg kg-1 i.v.), such inhibition increasing after intravenous administration of idazoxan. 4. All the antagonists used in our experiments failed to inhibit the pressor responses elicited by i.v. noradrenaline administration. 5. The above results suggest that the inhibitory effects of these 5-HT1 receptor antagonists are presynaptic in nature, but not related to the blockade of 5-HT1 receptors subtypes. The simultaneous activation or inhibition of other receptor systems could explain the inhibition produced by each 5-HT1 receptor antagonist studied.

  1. Effects of temperature during the irradiation of calcium carbonate

    Energy Technology Data Exchange (ETDEWEB)

    Negron M, A.; Camargo R, C.; Ramos B, S. [UNAM, Instituto de Ciencias Nucleares, Circuito Exterior, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Gomez V, V. [UNAM, Instituto de Quimica, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Uribe, R. M., E-mail: negron@nucleares.unam.mx [Kent State University, College of Technology, Kent 44240 Ohio (United States)

    2015-10-15

    The gamma irradiation of calcium carbonate at different doses (0 to 309 kGy) and temperature regimes (77 K to 298 K) was carried out to study the effects of irradiation temperature. The changes were followed by EPR spectroscopy. We observed the formation of a composite EPR spectrum even at low radiation doses and temperature. There is a strong effect on the evaluation of the radicals formed as a function of irradiation temperature, probably due to the diffusion in the frozen powder. Response curves show that this system tends to saturate at 10 MGy at 298 K. (Author)

  2. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia. PMID:27262216

  3. Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo

    International Nuclear Information System (INIS)

    Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand — rifampicin (300 mg/d) was given alone for 7 days in arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology. -- Highlights: ► The effects of SFN on PXR mediated CYP3A4 induction in humanized PXR mice and humans were examined. ► SFN had no effect on rifampicin mediated CYP3A4 induction in humans or humanized mice. ► SFN had a modest effect on basal CYP3A4 activity among subjects with higher baseline activity. ► Humanized PXR

  4. Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Poulton, Emma Jane [Center for Ecogenetics and Environmental Health, University of Washington (United States); Department of Environmental and Occupational Health Sciences, University of Washington (United States); Levy, Lisa [Public Health Sciences Division, Fred Hutchinson Cancer Research Center (United States); Lampe, Johanna W. [Center for Ecogenetics and Environmental Health, University of Washington (United States); Public Health Sciences Division, Fred Hutchinson Cancer Research Center (United States); Shen, Danny D. [Center for Ecogenetics and Environmental Health, University of Washington (United States); Department of Pharmaceutics, University of Washington (United States); Tracy, Julia [Center for Ecogenetics and Environmental Health, University of Washington (United States); Department of Environmental and Occupational Health Sciences, University of Washington (United States); Shuhart, Margaret C. [Division of Gastroenterology, Department of Medicine (United States); Thummel, Kenneth E. [Center for Ecogenetics and Environmental Health, University of Washington (United States); Department of Pharmaceutics, University of Washington (United States); Eaton, David L., E-mail: deaton@uw.edu [Center for Ecogenetics and Environmental Health, University of Washington (United States); Department of Environmental and Occupational Health Sciences, University of Washington (United States); Department of Pharmaceutics, University of Washington (United States)

    2013-01-01

    Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand — rifampicin (300 mg/d) was given alone for 7 days in arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology. -- Highlights: ► The effects of SFN on PXR mediated CYP3A4 induction in humanized PXR mice and humans were examined. ► SFN had no effect on rifampicin mediated CYP3A4 induction in humans or humanized mice. ► SFN had a modest effect on basal CYP3A4 activity among subjects with higher baseline activity. ► Humanized PXR

  5. Effects of calcium phosphate bioceramics on skeletal muscle cells.

    Science.gov (United States)

    Sun, J S; Tsuang, Y H; Yao, C H; Liu, H C; Lin, F H; Hang, Y S

    1997-02-01

    With advances in ceramics technology, calcium phosphate bioceramics have been applied as bone substitutes. The effects of implants on bony tissue have been investigated. The effects upon adjacent skeletal muscles have not been determined. The focus of this work is to elucidate the biological effects of various calcium phosphate bioceramics on skeletal muscles. Four different kinds of powder of calcium phosphate biomaterials including beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA), beta-dicalcium pyrophosphate (beta-DCP) and sintered beta-dicalcium pyrophosphate (SDCP), were tested by myoblast cell cultures. The results were analyzed by cell count, cell morphology and concentration of transforming growth factor beta 1 (TGF-beta 1) in culture medium. The cell population and TGF-beta 1 concentration of the control sample increased persistently as the time of culture increased. The changes in cell population and TGF-beta 1 concentration in culture medium of the beta-TCP and HA were quite low in the first 3 days of culture, then increased gradually toward the seventh day. The changes in cell population and TGF-beta 1 concentration in culture medium of the silica, beta-DCP, and SDCP were quite similar. They were lower during the first day of culture but increased and reached that of the control medium after 7 days' culture. Most cells on B-TCP and HA diminished in size with radially spread, long pseudopods. We conclude that HA and beta-TCP are thought to have an inhibitory effect on growth of the myoblasts. The HA and beta-TCP may interfere with the repair and regeneration of injured skeletal muscle after orthopedic surgery.

  6. EFFECTS OF PDGF-BB ON INTRACELLULAR CALCIUM CONCENTRATION AND PROLIFERATION IN CULTURED GLOMERULAR MESANGIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    WEN Li-ping; ZHANG Chong; BIAN Fan; ZOU Jun; JIANG Geng-ru; ZHU Han-wei

    2006-01-01

    Objective To investigate the relationship between the alteration of intracellular calcium concentration and proliferation in cultured glomerular mesangial cells. Methods Rat mesangial cells were cultured.Intracellular calcium concentrations were measured by confocal Laser Scanning Microscopy and Fura-3 fluorescence dyeing techniques. Cell growth was measured by MTT assay. Results PDGF-BB increased intracellular calcium concentrations in a dose-dependent manner, and at the same time promote the proliferation of mesangial cells. After preincubation with calcium channel blocker nifedipine or angiotensin converting enzyme inhibitor captopril, both the increase of intracellular calcium concentrations and cell proliferations induced by PDGF-BB were inhibited. Tripterigium Wilfordii Glycosides (TMG) significantly inhibited the mesangial cell proliferations, but it had no significant effect on intracellular calcium concentrations. Conclusion There was a positive relationship between the elevation of intracellular calcium concentration and cell proliferation in glomerular mesangial cells, but the increase of in- tracellular calcium concentrations wasn't the only way for proliferation.

  7. Effect of CuO on the Formation Mechanism of Calcium Sulphoaluminate

    Institute of Scientific and Technical Information of China (English)

    MA Suhua; SHEN Xiaohong; HUANG Yeping; ZHONG Baiqian

    2008-01-01

    Calcium sulphoaluminate was prepared with chemical reagents in this paper.The formation mechanism of calcium sulphoaluminate and effect of CuO on the formation mechanism of calcium sulphoaluminate were investigated by the chemical analysis,X-ray diffraction(XRD),and differential scanning calorimetry(DSC).The results show that there are three ways in the formation of calcium sulphoaluminate.CuO can promote the decomposition of calcium carbonate and decrease the formation temperature of calcium sulphoaluminate(C4A3S).When the burning temperature is below 1000℃,the addition of CuO can promote the formation of calcium sulphoaluminate,while CuO can not favor the formation of calcium sulphoaluminate above 1000℃.

  8. The Effects of NMDA Antagonists on Neuronal Activity in Cat Spinal Cord Evoked by Acute Inflammation in the Knee Joint.

    Science.gov (United States)

    Schaible, Hans-Georg; Grubb, Blair D.; Neugebauer, Volker; Oppmann, Maria

    1991-01-01

    In alpha-chloralose-anaesthetized, spinalized cats we examined the effects of NMDA antagonists on the discharges of 71 spinal neurons which had afferent input from the knee joint. These neurons were rendered hyperexcitable by acute arthritis in the knee induced by kaolin and carrageenan. They were located in the deep dorsal and ventral horn and some of them had ascending axons. The N-methyl-d-aspartate (NMDA) antagonists ketamine and d-2-amino-5-phosphonovalerate (AP5), were administered ionophoretically, and ketamine was also administered intravenously. In some of the experiments the antagonists were tested against the agonists NMDA and quisqualate. The effects of the NMDA antagonists consisted of a significant reduction in the resting activity of neurons and/or the responses of the same neurons to mechanical stimulation of the inflamed knee. Intravenous ketamine was most effective in suppressing the resting and mechanically evoked activity in 25 of 26 neurons tested. Ionophoretically applied ketamine had a suppressive effect in 11 of 21 neurons, and AP5 decreased activity in 17 of 24 cells. The reduction in the resting and/or the mechanically evoked discharges was achieved with doses of the antagonists which suppressed the responses to NMDA but not those to quisqualate. These results suggest that NMDA receptors are involved in the enhanced responses and basal activity of spinal neurons induced by inflammation in the periphery. PMID:12106256

  9. Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist.

    Directory of Open Access Journals (Sweden)

    Aaron S Coyner

    Full Text Available To assess the neuroprotective effects of flibanserin (formerly BIMT-17, a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model.Albino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections.A five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice.Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal

  10. Effect of pulse magnetic field stimulation on calcium channel current

    International Nuclear Information System (INIS)

    This study aimed to investigate the effect of low frequency and high amplitude pulse magnetic field (PMF) on Calcium ion channel current of cells. Measurements were done on the Human Embryonic Kidney 293 cells (HEK 293), which have only Calcium ion channels functioning. The whole cell current was measured by patch clamp method, with the clamped voltage ramping from −90 mV to +50 mV across the cell membrane. A PMF was generated by a 400-turn coil connected to a pulse current generator. The frequency of the pulse was 7 Hz, the width of the pulse was 3 ms, and the amplitude of the pulse, or the flux density, was ranging from 6 to 25 mT. The results showed that the profile of the whole cell Calcium channel current could be modified by the PMF. With the PMF applied, the phase shifting occurred: the onset of the channel opening took place several mili-seconds earlier than that without the PWF and correspondingly, the whole cell current reached its maximum earlier, and the current returned back to zero earlier as well. When the PWF was stopped, these effects persisted for a period of time, and then the current profile “recovered” to its original appearance. The decrease of the onset time and peak current time could be due to the local electric potential induced by the PWF and the direct interaction between PMF and ion channels/ions. The exact mechanisms of the observed effects of PMF on the cell are still unknown and need to be further studied.

  11. Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2

    Directory of Open Access Journals (Sweden)

    Riccardo Filadi

    2016-06-01

    Full Text Available Communication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2, mutations in which underlie familial Alzheimer’s disease (FAD, promotes ER-mitochondria coupling only in the presence of mitofusin 2 (Mfn2. PS2 is not necessary for the antagonistic effect of Mfn2 on organelle coupling, although its abundance can tune it. The two proteins physically interact, whereas their homologues Mfn1 and PS1 are dispensable for this interplay. Moreover, PS2 mutants associated with FAD are more effective than the wild-type form in modulating ER-mitochondria tethering because their binding to Mfn2 in mitochondria-associated membranes is favored. We propose a revised model for ER-mitochondria interaction to account for these findings and discuss possible implications for FAD pathogenesis.

  12. The rhizosphere effect on bacteria antagonistic towards the pathogenic fungus Verticillium differs depending on plant species and site.

    Science.gov (United States)

    Berg, Gabriele; Opelt, Katja; Zachow, Christin; Lottmann, Jana; Götz, Monika; Costa, Rodrigo; Smalla, Kornelia

    2006-05-01

    Rhizobacteria with antagonistic activity towards plant pathogens play an essential role in root growth and plant health and are influenced by plant species in their abundance and composition. To determine the extent of the effect of the plant species and of the site on the abundance and composition of bacteria with antagonistic activity towards Verticillium dahliae, bacteria isolated from the rhizosphere of two Verticillium host plants, oilseed rape and strawberry, and from bulk soil were analysed at three different locations in Germany over two growing seasons. A total of 6732 bacterial isolates screened for in vitro antagonism towards Verticillium resulted in 560 active isolates, among which Pseudomonas (77%) and Serratia (6%) were the most dominant genera. The rhizosphere effect on the antagonistic bacterial community was shown by an enhanced proportion of antagonistic isolates, by enrichment of specific amplified ribosomal DNA restriction analysis types, species and genotypes, and by a reduced diversity in the rhizosphere in comparison to bulk soil. Such an effect was influenced by the plant species and by the site of its cultivation. Altogether, 16S rRNA gene sequencing of 66 isolates resulted in the identification of 22 different species. Antagonists of the genus Serratia were preferentially isolated from oilseed rape rhizosphere, with the exception of one site. For isolates of Pseudomonas and Serratia, plant-specific and site-specific genotypes were found. PMID:16629754

  13. The effect of calcium and chitosan metabolism to the excretion of radiostrontium in mice

    International Nuclear Information System (INIS)

    Chitosan, a natural nontoxic chelator, was reported to reduce whole body retention of radiostrontium in mice. As calcium has a similar chemical properties to strontium both of which be easily bound with hydroxyapatite structure, calcium can be either a competitor or enhancer to chitosan on the removal of radiostrontium. We compared the effect of chitosan and calcium on the excretion of ingested radiostrontium (85Sr). Chitosan or calcium(CaCl2) and usual food was mixed as 1:99 by weight. The mixed food to chitosan(group 1) or calcium(group 2) were given orally for 30 days before 85Sr administration. In other groups, mixed calcium and chitosan solution (group 3), 1% calcium (group 4), or 1% chitosan solution (group 5) was given for 7 days immediately after oral administration of 85SrCl2 (0.25μCi). In control group, no chitosan or calcium were given. Either chitosan or calcium was effective on the removal of 85Sr from mouse body (Table 1). Addition of calcium on chitosan did not improve or deteriorate the effect of chitosan on the removal of 85Sr from mouse body. In conclusion, calcium was similarly effective on the removal of 85Sr from mouse body. (author)

  14. Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Su-Gang Shen; Dong Zhang; Heng-Tong Hu; Jun-Hui Li; Zheng Wang; Qing-Yong Ma

    2008-01-01

    AIM: To discuss the expression of α-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of α1- and α2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro.METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of α1- and α2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR).The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleoticlyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM).RESULTS: PC-2 expressed rnRNA in α1- and α2-adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However,exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine.Cell proliferation was inhibited by yohimbine via apoptosis induction.CONCLUSION: The expression of α1-and α2-adrenoreceptors is different in PC-2 and PC-3 cell lines,which might be indicative of their different functions. Theα2-adrenoceptor antagonist, yohimbine, can inhibit the proliferation of both cell lines and induce their apoptosis,suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells.

  15. Effect of dietary calcium: Phosphorus ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats.

    Science.gov (United States)

    Koshihara, Moyuru; Masuyama, Ritsuko; Uehara, Mariko; Suzuki, Kazuharu

    2004-01-01

    We investigated the effect of dietary calcium:phosphorus (Ca:P) ratio on bone mineralization and intestinal Ca absorption in ovariectomized (OVX) rat models of osteoporosis and sham-operated rats. Thirty 12-wk-old female Wistar rats were divided into three groups of OVX rats and three groups of sham rats. Thirty days after the adaptation period, OVX rats and sham rats were fed a diet formulated Ca:P, 1:0.5, 1:1 or 1:2 (each diet containing 0.5% Ca), respectively for 42 d. In both sham and OVX rats, serum osteocalcin, a marker of bone turnover, was increased by decreasing Ca:P ratio (1:2). In contrast, rats fed the Ca:P = 1:0.5 diet (dietary P restriction) suppressed the increased serum parathyroid hormone, osteocalcin and urinary deoxypyridinoline, and increased Ca absorption in both sham and OVX rats compared to the Ca:P = 1:1 and 1:2 diets. Especially, in OVX rats, the decreased bone mineral density of the fifth lumbar was also suppressed when rats were fed the Ca:P = 1:0.5 diet. These results indicated that the elevation of dietary Ca:P ratio may inhibit bone loss and increase intestinal Ca absorption in OVX rats.

  16. Effect of L-lactic acid on the absorption of calcium in gastrectomized rats.

    Science.gov (United States)

    Chonan, O; Takahashi, R; Yasui, H; Watanuki, M

    1998-12-01

    The effect of dietary L-lactic acid (LA), (0.5, 1.0, or 2.5 g/100 g of diet) on the absorption of calcium in gastrectomized rats was evaluated for 28 d. Calcium phosphate was used as a source of calcium. The apparent calcium absorption ratio and the calcium contents of the femur and tibia in gastrectomized rats fed the control diet were significantly less than those in sham-operated rats. In the gastrectomized rats, the apparent calcium absorption ratio and the calcium contents of bone in the rats fed the lower doses of LA diets (LA 0.5 or 1.0 g/100 g of diet) were not affected; however, the apparent calcium absorption ratio and the calcium contents of bone in the rats fed the highest doses of LA diet (LA 2.5 g/100 g of diet) were greater than those in gastrectomized rats fed the control diet. Dietary LA (2.5 g/100 g of diet) also enhanced the phosphorus absorption and bone phosphorus content in the gastrectomized rats. We speculated that the highest dose of dietary LA might be associated with the dissolving of a water-insoluble form of calcium salt in the diet, thereby facilitating the calcium absorption and resulting in increased bone calcium content in gastrectomized rats.

  17. Effect of Calcium Supplementation on Growth, Nutrient Digestibility and Fecal Lactobacilli in Dairy Calves

    Directory of Open Access Journals (Sweden)

    C. Yuangklang

    2010-01-01

    Full Text Available Problem statement: Based on earlier studies in veal calves and rats, the hypothesis tested was that high calcium intakes by ruminating dairy calves reduce fat digestibility, but do not affect growth performance due to enhanced colonization of the intestine with lactobacilli. Approach: In dairy calves that were fed on a combination of milk replacer, concentrate on grass hay, the effects of supplemental calcium on growth, nutrient digestibility and fecal lactobacilli were studied. Four concentrates with different levels of calcium were used. Results: Final body weight and weight gain were raised by the calcium level in the concentrate in a dose-dependent, linear fashion. Apparent digestibility of dry matter, organic matter, crude protein and crude fat were not influenced by the level of calcium in the concentrate. The number of fecal lactobacilli was significantly increased by higher dietary calcium levels, the effect having a linear trend. Calcium intake did not change the number of fecal E. coli. The apparent absorptions of calcium, phosphorus and magnesium were lowered in a linear, dose-dependent fashion by the calcium level in the concentrate. Conclusion: Increased calcium intakes stimulate weight gain in dairy calves fed a combination of milk replacer, concentrate and grass hay. This calcium effect may be related to an enhanced colonization of the intestine with lactobacilli.

  18. In vitro antagonistic growth effects of Lactobacillus fermentum and Lactobacillus salivarius and their fermentative broth on periodontal pathogens

    Directory of Open Access Journals (Sweden)

    Ling-Ju Chen

    2012-12-01

    Full Text Available As lactobacilli possess an antagonistic growth property, these bacteria may be beneficial as bioprotective agents for infection control. However, whether the antagonistic growth effects are attributed to the lactobacilli themselves or their fermentative broth remains unclear. The antagonistic growth effects of Lactobacillus salivarius and Lactobacillus fermentum as well as their fermentative broth were thus tested using both disc agar diffusion test and broth dilution method, and their effects on periodontal pathogens, including Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalisin vitro at different concentrations and for different time periods were also compared. Both Lactobacillus salivarius and Lactobacillus fermentum and their concentrated fermentative broth were shown to inhibit significantly the growth of Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis, althoughdifferent inhibitory effects were observed for different pathogens. The higher the counts of lactobacilli and the higher the folds of concentrated fermentative broth, the stronger the inhibitory effects are observed. The inhibitory effect is demonstrated to be dose-dependent. Moreover, for the lactobacilli themselves, Lactobacillus fermentum showed stronger inhibitory effects than Lactobacillus salivarius. However, the fermentative broth of Lactobacillus fermentum showed weaker inhibitory effects than that of Lactobacillus salivarius. These data suggested that lactobacilli and their fermentative broth exhibit antagonistic growth activity, and consumption of probiotics or their broth containing lactobacilli may benefit oral health.

  19. Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.

    Science.gov (United States)

    Thomsen, Morgane; Caine, Simon Barak

    2016-04-01

    Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. PMID:26874213

  20. Effect of Leukotriene Receptor Antagonist Montelukast Along with Curcumin against Gastric Ulceration

    Directory of Open Access Journals (Sweden)

    UM Viradia

    2011-07-01

    Full Text Available Curcumin, a yellow pigment in the spice turmeric, has been used for centuries as a treatment for inflammatory diseases. This yellow pigment has anti-secretary property in different experimental ulcer models. Montelukast, a leukotriene receptor antagonist has been used for the treatment of inflammatory disease. This substance has antioxidant property in different experimental models. This data supports to evaluate the synergistic effect of Montelukast along with Curcumin against gastric ulceration. Gastric ulcers were induced by administering Aspirin (200 mg/kg plus pylorus ligation and Indomethacin (20 mg/kg. Evaluation of Montelukast along with Curcumin was carried out in above experimental models. All the Montelukast (10 mg/kg along with Curcumin (60 mg/kg treated animals showed more significant reduction of ulcer index in both above experimental models compared to individual treatment with both, Curcumin and Montelukast.

  1. Antagonistic effect of fungi from Scots pine stump roots against Heterobasidion annosum and Armillaria ostoyae

    Directory of Open Access Journals (Sweden)

    Hanna Kwaśny

    2014-08-01

    Full Text Available The study presents quantitative and qualitative aspects of fungal colonization of the 2-year-old stump roots of the 30- and 49-year-old Scots pines, and biotic relations between fungi inhabiting the stump roots and major agent s of butt and root rot in Poland, i.e.: H. annosum and A. ostoyae. Compared to the live roots, the increase in density of fungi communities as well as the frequency of the fungi antagonistic towards H. annosum and A. ostoyae, particularly of Trichoderma species. in pine stump roots resulted in the increase of the suppressive effect of these communities towards both pathogens, studied in vitro. This finding may suggest a stronger resistance of pine stump roots to H. annosum and A. ostoyae what under forest conditions may be the example of natural control of both pathogens.

  2. Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones.

    Science.gov (United States)

    Massey, L K; Roman-Smith, H; Sutton, R A

    1993-08-01

    Dietary restriction of oxalate intake has been used as therapy to reduce the risk of recurrence of calcium oxalate kidney stones. Although urinary oxalate is derived predominantly from endogenous synthesis, it may also be affected by dietary intake of oxalate and calcium. The risk of increasing urinary oxalate excretion by excessive consumption of dietary oxalate is greatest in individuals with a high rate of oxalate absorption, both with and without overt intestinal disease. Although oxalate-rich foods enhanced excretion of urinary oxalate in normal volunteers, the increase was not proportional to the oxalate content of the food. Only eight foods--spinach, rhubarb, beets, nuts, chocolate, tea, wheat bran, and strawberries--caused a significant increase in urinary oxalate excretion. Restriction of dietary calcium enhances oxalate absorption and excretion, whereas an increase in calcium intake may reduce urinary oxalate excretion by binding more oxalate in the gut. This review of the literature indicates that initial dietary therapy for stone-forming individuals can be limited to the restriction of foods definitely shown to increase urinary oxalate. The effects of oxalate-restricted diets on urinary oxalate should be evaluated by means of laboratory analyses of urine composition. Subsequent long-term therapy can be recommended if beneficial results are obtained from oxalate restriction at an appropriate calcium intake. PMID:8335871

  3. Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Patel R

    2016-05-01

    Full Text Available Raj Patel Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, UK Abstract: Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE. For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. Keywords: venous thromboembolism, oral anticoagulant, prevention, treatment, primary

  4. Antagonist effect of interferon-γ aerosol inhalation on pulmonary remodeling after γ-ray irradiation

    International Nuclear Information System (INIS)

    Objective: To observe the antagonistic effect of interferon-y aerosol inhalation on pulmonary remodeling after γ-ray irradiation, and explore its mechanisms. Methods: The Wistar rats were randomly divided into irradiation control group and irradiation + Interferon-γ antagonist group, which proceeded IFN-γ aerosol inhalation 3 days before 20 Gy 60Co γ-ray irradiation, then were sacrificed at 10, 20, 30 days after irradiation. Conventional histopathological sections of lung tissue were prepared, which were stained immunohistochemically for α-SMA and Sirius red. The contents of collagen IV were determined by Western blot. The expression of MMP-2, MMP-9 and TIMP-1 in lung homogenate was detected by ELISA. Results: The widen degrees of interalveolar septum, the deposition of collagen I, III, and the expression of α-SMA decreased significantly in IFN-γ treatment group as compared with those in the irradiation control group. The expression of collagen IV appeared an elevation trend, but this phenomenon attenuated after IFN-γ was used. The levels of MMP-2 and TIMP-1 decreased 10 days after administration with IFN-γ but the opposite trend appeared for MMP- 9. The expression of MMP-2, MMP-9 and TIMP-1 decreased 30 days after administration with IFN-γ. Conclusion: IFN-γ is effective in alleviating pulmonary injuries induced by irradiation in rats, possibly by decreasing the expression of TIMP-1 to relieve the inhibition to MMP-9, then degrading collagen IV to antagonize remodeling after lung injury. (authors)

  5. Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence.

    Science.gov (United States)

    Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E

    2015-10-01

    An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.

  6. Effects of Dietary Calcium on Body Weight, Carcass Fat Content and Adipocyte Size in Male Rats

    OpenAIRE

    J Malekzadeh; SA Keshavarz; F Siassi; M Kadkhodaei; Eshraghian MR; AR Dorosti Motlagh; A Aliehpoor; M Chamari

    2006-01-01

    Introduction & Objective: Calcium is a micronutrient and now receiving much attention for its doubtful effects on weight and body fatness. A few mechanisms has been suggested for calcium effects on body fatness and the most emphasized one is the reducing of lipolysis and increasing lipogenesis via reducing parathyroid hormone levels. The present study is designed to evaluate the effects of nondairy dietary calcium on adipogenesis and adipocyte size in male Sprague dawley rats. Materials ...

  7. Effect of TNF antagonists on the productivity of daily work of patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Furuya H

    2013-01-01

    Full Text Available Hidekazu Furuya,1 Tsuyoshi Kasama,1 Takeo Isozaki,1,2 Masayu Umemura,1 Kumiko Otsuka,1 Sakiko Isojima,1 Hiroyuki Tsukamoto,1 TakehiroTokunaga,1 Ryo Yanai,1 Ryo Takahashi11Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan; 2Department of Rheumatology,University of Michigan Medical School, Ann Arbor, MI, USAAbstract: Rheumatoid arthritis (RA is a significant cause of work disability and job loss. The resulting economic burden experienced by patients has received considerable research attention. This research assesses the effect of tumor necrosis factor (TNF antagonists (infliximab, etanercept on the ability of RA patients living in Japan to work and participate in society. A total of 42 patients with active RA were enrolled and given biological therapy for 12 months (mo. Of these patients, 14 were employed full-time, 6 were employed part-time, and 22 were not employed. Twenty-six patients were given infliximab, and sixteen were given etanercept. The amount of domestic labor performed before the biologics served as a baseline and was assigned a value of 0%. After treatment with biologics, the productivity was evaluated using the visual analog scale (VAS; −100 to +100 mm. The administration of TNF antagonists to RA patients who exhibited an insufficient response to medical treatment significantly improved the Disease Activity Score 28 (DAS 28 after both 6 mo and 12 mo (P < 0.0001. A significant correlation was found between the improvement in their DAS 28 and improvements in their work situation (Productivity VAS (P < 0.05. Of particular interest is the significant correlation between the values of baseline mHAQ and the percent changes of Productivity VAS that was observed after 6 mo and 12 mo (P < 0.05. Our findings indicate that medical treatment of RA with TNF antagonists improves the patients' ability to perform their jobs and housekeeping. Because loss of productivity is an important

  8. The effect of glycosaminoglycans on the crystallisation of calcium oxalate.

    Science.gov (United States)

    Kohri, K; Garside, J; Blacklock, N J

    1989-06-01

    The effect of glycosaminoglycans on urinary stone formation was evaluated using a mixed suspension, mixed product removal (MSMPR) crystallisation system together with scanning electron microscopy (SEM) to examine the resulting crystals. Chondroitin sulphate was found to decrease the nucleation rate and to promote both the growth rate and suspension density. Results obtained with hyaluronic acid, although inconclusive, are similar to those given by chondroitin sulphate. Heparin sodium salt had a powerful inhibitory effect on both the nucleation rate and the suspension density, the effect increasing in proportion to the heparin concentration. SEM examination showed that the octahedral habit of calcium oxalate dihydrate was modified by the addition of heparin sodium salt and confirmed that the average crystal size in the presence of chondroitin sulphate and hyaluronic acid was significantly greater than the control or that found in the presence of heparin sodium salt. PMID:2502299

  9. Effect of the NMDA antagonist MK-801 on latent inhibition of fear conditioning.

    Science.gov (United States)

    Traverso, Luis M; Ruiz, Gabriel; De la Casa, Luis G

    2012-10-01

    N-methyl-D-aspartate (NMDA) receptors seem to play a central role in learning and memory processes involved in Latent Inhibition (LI). In fact, MK-801, a non-competitive NMDA receptor antagonist, has proved its effectiveness as a drug for attenuating LI when administered before or after stimulus preexposure and conditioning stages. This paper presents three experiments designed to analyze the effect of MK-801 on LI when the drug is administered before (Experiment 1A) or after (Experiment 1B) preexposure and conditioning stages with a conditioned emotional response procedure. Additionally, we analyze the effect of the drug when it was administered before preexposure, before conditioning or before both phases (Experiment 2). The results show that the effect of the drug varied as a function of the dose (with only the highest dose being effective), the moment of administration (with only the drug administered before the experimental treatments being effective), and the phase of procedure (reducing LI when the drug was administered only at preexposure, and disrupting fear conditioning when administered at conditioning). These differences may be due to several factors ranging from the role played by NMDA receptors in the processing of stimuli of different sensorial modalities to the molecular processes triggered by drug administration.

  10. Effects of chronic treatment with two selective 5-HT2 antagonists on sleep in the rat.

    Science.gov (United States)

    Pastel, R H; Echevarria, E; Cox, B; Blackburn, T P; Tortella, F C

    1993-04-01

    The effect of chronic administration of 2(2-dimethylaminoethylthio)-3-phenylquinoline (ICI-169,369) and 2(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline (ICI-170,809), two selective 5-HT2 antagonists, on sleep was studied in rats. As previously shown, the acute effect of ICI-170,809 was to increase latency to rapid eye movement sleep (REMS), decrease the number of REM periods (REMPs), suppress the cumulative amount of REMS over 12 h, and increase the duration of REMPs in the first 6 h, while having no effect on non-REM sleep (NREMS). Administration of ICI-169,369 had similar effects except no change was seen in the duration of REMPs and cumulative REMS was suppressed for 24 h. When given 2 x daily for 5 days, tolerance to the REMS suppressant effects developed in both drugs. After discontinuation of treatment, a REMS rebound occurred after ICI-170,809, but not ICI-169,369. No significant effect on NREMS was seen after administration of ICI-170,809, whereas ICI-169,369 lowered 24-h cumulative NREMS on the fifth day of administration.

  11. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    Science.gov (United States)

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat

    2016-01-01

    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID:27679825

  12. Effects of calcium on intestinal mucin: implications for cystic fibrosis.

    Science.gov (United States)

    Forstner, J F; Forstner, G G

    1976-06-01

    A major feature of the disease cystic fibrosis is the excessive concentration of mucus within ducts and glands of mucous-producing organs. Some mucous secretions also show an elevation in calcium concentration. Using purified rat intestinal goblet cell mucin as a model mucin, we have investigated the effect of millimolar additions (1-25 mM) of CaCl2 on the physical properties of the mucin. Isotonicity of incubation media was preserved in order to mimic in vivo conditions. CaCl2 (8-15mM) caused a 15-33% decrease in viscosity, no change in electrophoretic mobility in acrylamide gels, and a 20-30% decrease in solubility of the mucin. Solubility changes were reversed by the addition of EDTA (20 mM) to incubations. Insolubility was also produced in incubations of mucin with a mixture of soluble intestinal contents (NaCl washings). These findings strongly suggest that the mucin became smaller and more dense as calcium was added, a process most probably achieved by loss of intramolecular water. PMID:1272637

  13. The effect of calciums on molecular motions of proteinase K.

    Science.gov (United States)

    Liu, Shu-Qun; Tao, Yan; Meng, Zhao-Hui; Fu, Yun-Xin; Zhang, Ke-Qin

    2011-02-01

    The native serine protease proteinase K binds two calcium cations. It has been reported that Ca(2+) removal decreased the enzyme's thermal stability and to some extent the substrate affinity, but has discrepant effects on catalytic activity of the enzyme. Molecular dynamics simulations were performed on the Ca(2+)-bound and Ca(2+)-free proteases to investigate the mechanism by which the calciums affect the structural stability, molecular motions, and catalytic activity of proteinase K. Very similar structural properties were observed between these two forms of proteinase K during simulations; and several long-lived hydrogen bonds and salt bridges common to both forms of proteinase K were found to be crucial in maintaining the local conformations around these two Ca(2+) sites. Although Ca(2+) removal enhanced the overall flexibility of proteinase K, the flexibility in a limited number of segments surrounding the substrate-binding pockets decreased. The largest differences in the equilibrium structures of the two simulations indicate that, upon the removal of Ca(2+), the large concerted motion originating from the Ca1 site can transmit to the substrate-binding regions but not to the catalytic triad residues. In conjunction with the large overlap of the essential subspaces between the two simulations, these results not only provide insight into the dynamics of the underlying molecular mechanism responsible for the unchanged enzymatic activity as well as the decreased thermal stability and substrate affinity of proteinase K upon Ca(2+) removal, but also complement the experimentally determined structural and biochemical data.

  14. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    Directory of Open Access Journals (Sweden)

    James P Kemp

    2009-11-01

    Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

  15. Reevaluation of the effect of calcium ions on auxin-induced elongation

    Energy Technology Data Exchange (ETDEWEB)

    Cleland, R.E. (Univ. of Washington, Seattle); Rayle, D.L.

    1977-01-01

    The mechanism by which calcium ions inhibit cell elongation has been reinvestigated. Growth-inhibiting levels of calcium, when applied to isolated walls (in vitro treatment) do not decrease cell wall extensibility as measured by the Instron technique. Thus, the hypothesis that calcium inhibits growth by forming wall-stiffening calcium bridges must be abandoned. Treatment of living auxin-treated sections with calcium (in vivo treatment) does cause a decrease in the subsequently measured wall extensibility, but this decline appears to be simply a consequence of the growth inhibition rather that its cause. Growth-inhibiting levels of calcium do not appreciably reduce the rate of auxin-enhanced H+ excretion. Pretreatment with calcium does not reduce the capacity of walls to undergo acid-activated wall loosening in the absence of calcium. High concentrations of CaC1/sub 2/ (0.02 M) cause an initial elastic shrinkage of Avena sections comparable to that caused by the same osmolarity of mannitol, but the subsequent growth inhibition is to great to be explained by an osmotic inhibition.Calcium ions do inhibit H+-induced extension of frozen-thawed sections under tension. The growth-inhibitory effects of calcium, then, may be ascribed to a direct inhibition exerted by calcium ions on the H+-induced wall-loosening process.

  16. Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on antinociception of propofol

    Institute of Scientific and Technical Information of China (English)

    Ai-junXU; Shi-mingDUAN; Yin-mingZENG

    2004-01-01

    AIM: To study the effects of intrathecal (it) agonists and antagonists of N-methyl-D-aspartate (NMDA) and alphaamino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors and NMDAR1 antisense oligodeoxynucleotides (AS ODN) on the antinociception of propofol. METHODS: Hot-plate test (HPPT) and acetic acid-induced writhing test were used to measure the nociceptive thresholds in mice. The effects of intrathecal NMDA, AMPA, MK-801, NBQX, or NMDAR1 AS ODN on the antinociception of propofol were observed.RESULTS: Propofol (25, 50 mg/kg, ip) displayed an appreciable antinociceptive effect in hot-plate test and acetic acid-induced writhing test. NMDA (12.5, 25 ng, it) or AMPA (1.25, 2.5 ng, it) exhibited no effects on the behavior but decreased HPPT significantly compared with basal HPPT and aCSF group (P<0.05, P<0.01). No effects on behavior and HPPT were obtained in NMDA (6.25 ng, it) or AMPA (0.625 ng, it) groups. NMDA (6.25, 12.5, and 25 ng, it) dose-dependently decreased the HPPT in propofol-treated group. AMPA (1.25, 2.5 ng, it) also decreased HPPT significantly. MK-801 (0.25, 0.5 μg, it) or NBQX (0.25, 0.5 μg, it) groups had no behavioral changes, two antagonists 0.5 μg but not 0.25 μg increased HPPT in conscious or propofol-treated mice. AS ODN (5, 10, and 20 μg, it) groups exhibited dose-dependent increased in HPPT in propofol-treated groups compared with aCSF group(P<0.05, P<0.01). CONCLUSION: Both agonists NMDA and AMPA reversed the antinociception of propofol.MK-801, NBQX, and NMDAR1 AS ODN potentiated the antinociceptive effects of propofol. Propofol produced antinociception through an interaction with spinal NMDA and AMPA receptors in mice.

  17. The Effect of Calcium on the Binding of Calmodulin to Calcium/Calmodulin Protein Kinase II.

    Science.gov (United States)

    Porta, Angela R.

    2000-01-01

    Introduces a follow-up laboratory experiment demonstrating the formation change when calcium binds to calmodulin. This conformation change allows this complex to bind to a target protein. Presents the necessary information to conduct the experiment and discusses the results. (YDS)

  18. How synergistic or antagonistic effects may influence the mutual hazard ranking of chemicals

    Directory of Open Access Journals (Sweden)

    Lars Carlsen

    2015-04-01

    Full Text Available The presence of various agents, including humic materials, nanomaterials, microplastics, or simply specific chemical compounds, may cause changes in the apparent persistence, bioaccumulation, and/or toxicity (PBT of a chemical compound leading to an either increased or decreased PBT characteristics and thus an increased or decreased hazard evaluation. In the present paper, a series chloro-containing obsolete pesticides is studied as an illustrative example. Partial order methodology is used to quantify how changed P, B, or T characteristics of methoxychlor (MEC influences the measure of the hazard of MEC, relative to the other 11 compounds in the series investigated. Not surprisingly, an increase in one of the three indicators (P, B, or T lead to an increased average order and thus an increased relative hazard as a result of a synergistic effect. A decrease in one of the indicator values analogously causes a decreased average order/relative hazard through an antagonistic effect; the effect, however, being less pronounced. It is further seen that the effect of changing the apparent value of the three indicators is different. Thus, persistence apparently is more important that bioaccumulation which again appears more important than toxicity, which is in agreement with previous work. The results are discussed with reference to the European chemicals framework on registration, evaluation and authorization of chemicals (REACH framework.

  19. The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors

    OpenAIRE

    Herold, Christopher L; Behm, David J.; Buckley, Peter T.; Foley, James J; William E Wixted; Sarau, Henry M; Douglas, Stephen A

    2003-01-01

    The functional activity of the peptidic neuromedin B receptor antagonist BIM-23127 was investigated at recombinant and native urotensin-II receptors (UT receptors). Human urotensin-II (hU-II) promoted intracellular calcium mobilization in HEK293 cells expressing the human UT (hUT) or rat UT (rUT) receptors with pEC50 values of 9.80±0.34 (n=6) and 9.06±0.32 (n=4), respectively. While BIM-23127 alone had no effect on calcium responses in either cell line, it was a potent and competitive antagon...

  20. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

    Science.gov (United States)

    Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

    2014-11-01

    Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

  1. Effect of calcium source on structure and properties of sol-gel derived bioactive glasses.

    Science.gov (United States)

    Yu, Bobo; Turdean-Ionescu, Claudia A; Martin, Richard A; Newport, Robert J; Hanna, John V; Smith, Mark E; Jones, Julian R

    2012-12-18

    The aim was to determine the most effective calcium precursor for synthesis of sol-gel hybrids and for improving homogeneity of sol-gel bioactive glasses. Sol-gel derived bioactive calcium silicate glasses are one of the most promising materials for bone regeneration. Inorganic/organic hybrid materials, which are synthesized by incorporating a polymer into the sol-gel process, have also recently been produced to improve toughness. Calcium nitrate is conventionally used as the calcium source, but it has several disadvantages. Calcium nitrate causes inhomogeneity by forming calcium-rich regions, and it requires high temperature treatment (>400 °C) for calcium to be incorporated into the silicate network. Nitrates are also toxic and need to be burnt off. Calcium nitrate therefore cannot be used in the synthesis of hybrids as the highest temperature used in the process is typically 40-60 °C. Therefore, a different precursor is needed that can incorporate calcium into the silica network and enhance the homogeneity of the glasses at low (room) temperature. In this work, calcium methoxyethoxide (CME) was used to synthesize sol-gel bioactive glasses with a range of final processing temperatures from 60 to 800 °C. Comparison is made between the use of CME and calcium chloride and calcium nitrate. Using advanced probe techniques, the temperature at which Ca is incorporated into the network was identified for 70S30C (70 mol % SiO(2), 30 mol % CaO) for each of the calcium precursors. When CaCl(2) was used, the Ca did not seem to enter the network at any of the temperatures used. In contrast, Ca from CME entered the silica network at room temperature, as confirmed by X-ray diffraction, (29)Si magic angle spinning nuclear magnetic resonance spectroscopy, and dissolution studies. CME should be used in preference to calcium salts for hybrid synthesis and may improve homogeneity of sol-gel glasses.

  2. Effects of 2,3-benzodiazepine AMPA receptor antagonists on dopamine turnover in the striatum of rats with experimental parkinsonism.

    Science.gov (United States)

    Megyeri, Katalin; Marko, Bernadett; Sziray, Nora; Gacsalyi, Istvan; Juranyi, Zsolt; Levay, Gyorgy; Harsing, Laszlo G

    2007-03-15

    Although levodopa is the current "gold standard" for treatment of Parkinson's disease, there has been disputation on whether AMPA receptor antagonists can be used as adjuvant therapy to improve the effects of levodopa. Systemic administration of levodopa, the precursor of dopamine, increases brain dopamine turnover rate and this elevated turnover is believed to be essential for successful treatment of Parkinson's disease. However, long-term treatment of patients with levodopa often leads to development of dyskinesia. Therefore, drugs that feature potentiation of dopamine turnover rate and are able to reduce daily levodopa dosages might be used as adjuvant in the treatment of patients suffering from Parkinson's disease. To investigate such combined treatment, we have examined the effects of two non-competitive AMPA receptor antagonists, GYKI-52466 and GYKI-53405, alone or in combination with levodopa on dopamine turnover rate in 6-hydroxydopamine-lesioned striatum of the rat. We found here that repeated administration of levodopa, added with the peripheral DOPA decarboxylase inhibitor carbidopa, increased dopamine turnover rate after lesioning the striatum with 6-hydroxydopamine. Moreover, combination of levodopa with GYKI-52466 or GYKI-53405 further increased dopamine turnover enhanced by levodopa administration while the AMPA receptor antagonists by themselves failed to influence striatal dopamine turnover. We concluded from the present data that potentiation observed between levodopa and AMPA receptor antagonists may reflect levodopa-sparing effects in clinical treatment indicating the therapeutic potential of such combination in the management of Parkinson's disease.

  3. ANTIBACTERIAL EFFECT OF CALCIUM HYDROXIDE IN DIFFER ENT VEHICLES

    Directory of Open Access Journals (Sweden)

    Hari

    2012-11-01

    Full Text Available ABSTRACT: AIM: This study evaluated the antibacterial effect of ca lcium hydroxide in different vehicles in an in vitro model. MATERIAL AND METHODS: Calcium hydroxide paste prepared with two conventionally used vehicles namely, campho rated monochlophenol, distilled water and also propylene glycol. The antibacterial activity of these paste were tested against five micro- organisms that can commonly occur in the inf ected root canals. RESULTS AND CONCLUSIONS: The results of the study indicate that a paste of ca lcium hydroxide made with propylene glycol exerts significant antibacterial act ion. Hence, it can be recommended for use as an intracanal medicament in preference to a paste prepa red with a tissue toxic phenolic compound like camphorated mono chlorophenol

  4. Effects of β2-Adrenergic Antagonist on Cytosolic Ca2+ in Ventricular Myocytes from Infarcted Rat Heart

    Institute of Scientific and Technical Information of China (English)

    Yang Hui; Wu Wei; Zeng Chong; Deng Chunyu; Fang Chang; Chen Shanming

    2006-01-01

    Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca2 +([Ca2+]i) in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated.Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction (MI) and [Ca2+]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absenceof beta1-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1,2- adrenergic antagonists propranolol was examined.Results The followings were found that ICI11 8, 551 had no significant effects on the rise of [Ca2+]i induced by isoproterenol in normal ventricular myocytes (P >0.05), ICI118, 551 only significantly attenuated the rise of [Ca2+]i induced by isoproterenol at four weeks and eight weeks after MI (24.5% ±5.7% vs 57.8% ±13.2%, P< 0.01; 12.2%±7.9% vs 44.6%±11.3%, P<0.01). Atenolol had suppressive effects only in the control group and the post-MI group of two weeks (P<0.05), and propranolol had suppressive effects in the control and all the three post-MI groups (P<0.01).Conclusions Beta2-adrenergic antagonist ICI118,551 may exert negative effects on Ca2+ overload initiated by sympathetic stimulation after MI.

  5. Anti-arrhythmic and electrophysiological effects of the endothelin receptor antagonists, BQ-123 and PD161721.

    Science.gov (United States)

    Crockett, T R; Scott, G A; McGowan, N W; Kane, K A; Wainwright, C L

    2001-11-30

    The effects of the endothelin ET(A), (BQ-123) and endothelin ET(A/B) (PD161721) receptor antagonists were investigated on ischaemia-induced arrhythmias and on the maximum following frequency. The study was carried out in Langendorff perfused rat hearts subjected to coronary artery occlusion in which the severity of arrhythmias, coronary perfusion pressure and heart rate were measured. The % incidence of ischaemia-induced irreversible ventricular fibrillation (ventricular fibrillation) was reduced significantly from 58%, in control rat hearts, to 0% (at 10(-7) and 10(-6) M PD161721 and 10(-6) M BQ-123 PHz, respectively (PHz) than in normal [K(+)] (from 9.0+/-0.3 to 4.9+/-0.5 Hz). In conclusion, both BQ-123 and PD161721 had an anti-fibrillatory effect in isolated rat hearts that may be due, at least in part, to an ability to reduce the maximum following frequency. This latter effect is unlikely to be due to Na(+) channel blockade since it was not markedly potentiated by elevation of extracellular [K(+)].

  6. Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring.

    Science.gov (United States)

    Koenig, John R; Liu, Huaqing; Drizin, Irene; Witte, David G; Carr, Tracy L; Manelli, Arlene M; Milicic, Ivan; Strakhova, Marina I; Miller, Thomas R; Esbenshade, Timothy A; Brioni, Jorge D; Cowart, Marlon

    2010-03-15

    Three novel series of histamine H(4) receptor (H(4)R) antagonists containing the 2-aminopyrimidine motif are reported. The best of these compounds display good in vitro potency in both functional and binding assays. In addition, representative compounds are able to completely block itch responses when dosed ip in a mouse model of H(4)-agonist induced scratching, thus demonstrating their activities as H(4)R antagonists. PMID:20171098

  7. Effect of meal composition on calcium absorption: enhancing effect of carbohydrate polymers

    International Nuclear Information System (INIS)

    Meal components including fat, fiber, and carbohydrates can influence the intestinal absorption of calcium; such interactions may be of even greater importance in the presence of intestinal disease. This study compares intestinal absorption of 47CaCl2 administered in four ways: in water, within a standard meal, with a liquid formula (Ensure, Ross Laboratories, Columbus, Ohio), or with a glucose polymer solution (Frodex-15, Ross). Studies were carried out in 9 patients with ileal resection, 3 patients with jejunoileal bypass, and 14 controls. Fractional calcium absorption from water was lower in patients than in controls. Absorption was enhanced 1.5- to 5-fold when 47CaCl2 was administered with a liquid formula diet containing a glucose polymer or with the glucose polymer alone. Patients with the lowest calcium absorption from breakfast showed the greatest effect of calcium ingestion with formula or glucose polymer. These findings further emphasize the importance of meal composition on calcium absorption and provide a possible mechanism for enhancing calcium absorption in some patients with chronically impaired absorption

  8. MECHANISM OF THE PROTECTIVE EFFECT OF SUPPLEMENTAL DIETARY CALCIUM ON CYTOLYTIC ACTIVITY OF FECAL WATER

    NARCIS (Netherlands)

    LAPRE, JA; DEVRIES, HT; TERMONT, DSML; KLEIBEUKER, JH; DEVRIES, EGE; VANDERMEER, R

    1993-01-01

    Dietary calcium supplementation inhibits hyperproliferation of rectal epithelium, possibly by precipitating luminal surfactants and thus preventing their cell-damaging effects. Therefore, we studied the effects of supplemental dietary calcium (35.5 mmol/day) on composition and cytolytic activity of

  9. Influence of slow calcium channel inhibitors on radioprotective effect of phenilephrine

    International Nuclear Information System (INIS)

    Verapamil and cinnarizine decrease radioprotective effect of phenylephrine, but nifedipin (more specific inhibitor of slow calcium channel) dosesn't change it. Consequently, protective effect of phenylephine isn't realized by influx of Ca2+ ions through slow calcium channel

  10. In vitro effect of wheat bran (Triticum aestivum) extract on calcium oxalate urolithiasis crystallization.

    Science.gov (United States)

    Sekkoum, Khaled; Cheriti, Abdelkrim; Taleb, Safia

    2011-10-01

    Urolithiasis can lead to the loss of renal function in some cases. In this study, we tested the inhibiting effect of wheat bran (Triticum aestivum L) extract on calcium oxalate crystallization in a turbidimetric model, by FTIR spectroscopy, and polarized microscopy. The results show that this plant extract has a major inhibitory effect on calcium oxalate crystallization. PMID:22164778

  11. Effect of GABAB Receptor Antagonist (CGP35348 on Learning and Memory in Albino Mice

    Directory of Open Access Journals (Sweden)

    Quratulane Gillani

    2014-01-01

    Full Text Available The present study was designed to demonstrate the potential effect of CGP 35348 (GABAB receptor antagonist on the learning, memory formation, and neuromuscular coordination in albino mouse. Mice were intrapertoneally injected with 1 mg CGP 35348/mL of distilled water/Kg body weight, while the control animals were injected with equal volume of saline solution. A battery of neurological tests was applied following the intrapertoneal injections. Results of rota rod indicated that CGP 35348 had no effect on neuromuscular coordination in both male (P=0.528 and female (P=0.125 albino mice. CGP 35348 treated females demonstrated poor exploratory behavior during open filed for several parameters (time mobile (P=0.04, time immobile (P=0.04, rotations (P=0.04, and anticlockwise rotations (P=0.038. The results for Morris water maze (MWM retention phase indicated that CGP 35348 treated male mice took shorter latency to reach the hidden platform (P=0.04 than control indicating improved memory. This observation was complemented by the swim strategies used by mice during training days in MWM as CGP 35348 treated males used more direct and focal approach to reach the platform as the training proceeded.

  12. EFFECT OF ELECTROACUPUNCTURE AND CALCIUM-CHANNEL INHIBITORS ON CYTOPLASMIC FREE CALCIUM CONCENTRATION OF MOUSE BRAIN CELLS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ming-mei; XIE Ji-min; CHEN Min; ZHANG Yan

    2005-01-01

    Objective: To study the effect of electroacupuncture (EA) and Verapamil and Nifedipine (calcium channel inhibitors) on free calcium concentrations of cells and intrasynaptosomes in hypothalamus (HT), periaqueductual grey matter (PAG) and hippocampus (HIP) of mice. Methods: The female ICR mice were randomly divided into control, EA, CaCl2 and CaCl2+EA groups (n=8 in each group). Pain threshold was detected by using radiation-heat irradiation-induced tail flick method. EA (8 Hz, a suitable stimulating strength, dense-sparse waves and duration of 30 min) was applied to"Shuigou" (水沟 GV 26) and "Chengjiang" (承浆CV 24). CaCl2 (10 μL, 0.2 μmol/L) was injected into the lateral cerebral ventricle of mice after EA. The concentrations of cytosolic free calcium ([Ca2+]i) in HIP, PAG, HT cell suspension specimen and hippocampal intrasynaptosome suspension of mice were determined by the fluorescent calcium indicator Fura-2-AM and a spectrofluorometer. Results: During EA analgesia, the intracellular free [Ca2+]i in HT and PAG specimens and intrsynaptosomal [Ca2+]i of the 3 cerebral regions decreased considerably (P<0.05~0.01), but that in hippocampal cell suspension increased significantly (P<0.01) in comparison with control group. The concentrations of hippocampal intrasynaptosomal free [Ca2+]i decreased significantly after adding Verapamil and Nifedipine to the extracted hippocampal intrasynaptosomal specimen. Microinjection of CaCl2 into lateral ventricle had no apparent influence on degree of analgesia (DA)% and intracellular and intrasynapsotomal [Ca2+]i, but significantly lower DA% and reduce changes of cytosolic and intrasynaptosomal [Ca2+]i induced by EA stimulation. Conclusion: Calcium ion in the neurons and intrasynaptosome of HT, PAG and HIP is involved in electroacupuncture analgesia.

  13. Effect of Cationic and Anionic Surfactants on the Application of Calcium Carbonate Nanoparticles in Paper Coating

    CERN Document Server

    Barhoum, Ahmed; Abou-Zaied, Ragab Esmail; Rehan, Mohamed; Dufour, Thierry; Hill, Gavin; Dufresne, Alain

    2016-01-01

    Modification of calcium carbonate particles with surfactant significantly improves the properties of the calcium carbonate coating on paper. Unmodified and CTAB and oleate-modified calcium carbonate nanoparticles were prepared using the wet carbonation technique for paper coating. CTAB (cationic surfactant) and sodium oleate (anionic surfactant) were used to modify the size, morphology, and surface properties of the precipitated nanoparticles. The obtained particles were characterized by XRD, FT-IR spectroscopy, zeta potential measurements, TGA and TEM. Coating colors were formulated from the prepared unmodified and modified calcium carbonates and examined by creating a thin coating layer on reference paper. The effect of calcium carbonate particle size and surface modification on paper properties, such as coating thickness, coating weight, surface roughness, air permeability, brightness, whiteness, opacity, and hydrophobicity, were investigated and compared with GCC calcium carbonate-coated papers. The obtai...

  14. Effect of high calcium concentration influents on enhanced biological phosphorus removal process

    International Nuclear Information System (INIS)

    In this work, the effect of calcium concentration in wastewater on the polyphosphate accumulating organisms (PAO) is investigated as well as its influence in PAO metabolism, specifically in the YPO4 (ratio between phosphorus release and acetic acid uptake). For this study a sequencing batch reactor (SBR) anaerobic-aerobic was used, in which the PAO enriched biomass was exposed to different calcium concentrations in the influent wastewater. The results indicate that until a given calcium level in the influent wastewater (35 mg Ca/l) the metabolism is not affect, but higher calcium concentrations lead to significant YPO4 decline. (Author) 18 refs.

  15. Effect of calcium on cell-wall degrading enzymes of Botrytis cinerea.

    Science.gov (United States)

    Sasanuma, Izumi; Suzuki, Takuya

    2016-09-01

    Effective anti-Botrytis strategies leading to reduce pesticides on strawberries are examined to provide the protection that is harmless to humans, higher animals and plants. Calcium treatments significantly inhibited the spore germination and mycelial growth of B. cinerea. The intracellular polygalacturonase and CMCase showed low activities in B. cinerea cultivated by medium containing calcium. On the other hand, calcium-stimulated β-glucosidases production occurred. Our findings suggest that the calcium treatments keep CMCase activity low and cause low activities of cell-wall degrading enzymes of B. cinerea in the late stage of growth. PMID:26998660

  16. Does calcium contribute to the effectiveness of a coagulum for pyelolithotomy?

    Science.gov (United States)

    Watson, G M; Wickham, J E; Colvin, B T

    1984-04-01

    Adding calcium to a mixture of thrombin and fibrinogen increased the breaking strain of the resultant coagulum by 10-fold, but did not significantly reduce the length to which it could be stretched. There was no detectable change in the time taken for the coagulum to dissolve in urine. Simulation pyelolithotomies were performed on pig kidneys containing ball-bearings which represented calculi. Coagula formed with calcium were significantly more effective at retrieving the ball-bearings than coagula without calcium. It is concluded that the ideal coagulum formula should include 1 mmol of calcium. PMID:6498432

  17. INTRACEREBROVENTRICULAR APPLICATION OF COMPETITIVE AND NONCOMPETITIVE NMDA ANTAGONISTS INDUCE SIMILAR EFFECTS UPON RAT HIPPOCAMPAL ELECTROENCEPHALOGRAM AND LOCAL CEREBRAL GLUCOSE-UTILIZATION

    NARCIS (Netherlands)

    BODDEKE, HWGM; WIEDERHOLD, KH; PALACIOS, JM

    1992-01-01

    In this study we have used electrophysiological and metabolic markers to investigate the effects of competitive and non-competitive NMDA antagonists in rats after central or peripheral administration. The non-competitive antagonist, MK-801, induced dose-dependent suppression of rat hippocampal EEG e

  18. Effects of dopamine D4 receptor antagonist on spontaneous alternation in rats

    Directory of Open Access Journals (Sweden)

    Lind Nanna M

    2008-10-01

    Full Text Available Abstract Background The present study was a component of a series of studies scrutinising the neuroreceptor substrate of behavioural flexibility in a rat model. Spontaneous alternation paradigms model the natural tendency of rodents to spontaneously and flexibly shift between alternative spatial responses. In the study it was tested for the first time if the neurochemical substrate mediating spontaneous alternation behaviour includes the dopamine D4 receptor. Methods The acute effects of the highly selective dopamine D4 receptor antagonist L-745,870 on rats' performance in a spontaneous alternation paradigm in a T-maze were examined. The paradigm was a food-rewarded continuous trial procedure performed for 20 trials. Results The spontaneous alternation rate was not affected by the doses of the drug administered (0.02 mg/kg; 0.2 mg/kg; 2 mg/kg, but the position bias of the group receiving the highest L-745,870 dose (2 mg/kg was significantly increased compared to the group that received the lowest dose (0.02 mg/kg. No significant effects on position bias were found compared to saline. The drug did not increase response perseveration. Conclusion The results show that the neural substrate mediating the spatial distribution of responses in the spontaneous alternation paradigm includes the D4 receptor. However, the statistically significant effect of L-745,870 on position bias was found comparing a high drug dose with a low drug dose, and not comparing the drug doses with saline. For the tested doses of L-745,870 the effect on position bias was not large enough to affect the alternation rate.

  19. Effect of gonadal hormones on hypophagic property of opioid antagonist Naloxone

    Directory of Open Access Journals (Sweden)

    Gargate Ashwini R, Kulkarni Dushant V

    2014-03-01

    Full Text Available Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these Gonadal hormones interact with Opioid receptors to modulate food intake. Objective: The aim of the study was to find out how Gonadal hormones affect hypophagic property of Naloxone. Methods: Basal food intake of 40 healthy adult females and 20 healthy adult male rats was recorded. Then they were injected intraperitoneally with Naloxone after fasting for 24 hrs. In female rats food intake was measured during different phases of the estrous cycle. All the rats were then subjected to gonadectomy. The food intake was measured after gonadectomy. The effect of Naloxone was also measured in deprivation paradigm after gonadectomy. Results: Female rats showed decreased food intake during proestrous and estrous phases. In female rats there was no hypophagia after Naloxone injection during these phases. Male rats showed hypophagia on Naloxone injection. Male rats showed increased food intake after gonadectomy. In female rats the increase in food intake was not significant when gonadectomy was done during metestrous and diestrous. However, Naloxone could induce hypophagia in all female rats after gonadectomy. Conclusion: Estrogen decreases food intake, it decreases sensitivity of female rats to hypophasic effects of Naloxone. Testosterone decreases food intake. Testosterone does not interfere with hypophagic effect of Naloxone.

  20. Effect of high dietary calcium on weight management in rats

    International Nuclear Information System (INIS)

    The present study was undertaken to find out a suitable dietary regime to maintain a lower prevalence of overweight or obesity by adjusting the diet components. Therefore, male Swiss albino rats were selected according to their ages and divided into two main groups, i.e., premature and mature groups. Each rat group was divided into 4 subgroups and each subgroup was fed on a diet of varied composition. Serum levels of lipids, calcium, phosphorous and testosterone were determined in addition to body weight measurement. The results indicate non-significant decrease of percentage of body weight gain in premature rats fed on high-calcium diets while significant decrease of percentage of body weight gain in mature rats fed on the same diet composition. The levels of serum HDL-C, LDL-C, triglycerides and testosterone were significantly decreased in premature rats fed high- calcium diets. In premature rats, only rat subgroup fed on high calcium from milk, showed a significant decrease in serum cholesterol levels. Calcium and phosphorus levels exhibited non- significant change between premature rats. In mature rats, LDL-C data demonstrate nonsignificant changes while cholesterol and triglyceride levels were significantly decreased in rats fed high -calcium diet compared to control. HDL-C level revealed a significant decrease in sera of mature rats fed on high calcium from milk. Serum testosterone levels were significantly decreased in mature rats fed low- fat diets or low fat diets supplemented with high- calcium level. In general, one would suggest to consume low fat diet (4%) supplemented with high calcium from dry skimmed milk fortified with hydroxyapatite as suitable dietary program to avoid overweight or obesity.

  1. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma.

    Science.gov (United States)

    Bisgaard, H

    2001-01-01

    Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability, exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce ciliary motility, which may hinder mucociliary clearance. Asthmatic patients demonstrate increased production of cysteinyl leukotrienes during naturally occurring asthma and acute asthma attacks as well as after allergen and exercise challenge. The leukotriene receptor antagonists montelukast, zafirlukast and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate of airway inflammation, are decreased during montelukast treatment in children. Cysteinyl leukotriene synthesis is not blocked by corticosteroid therapy. This important observation suggests that the leukotriene receptor antagonists represent a novel therapeutic approach, one that may provide benefits that are additive with corticosteroid therapy. This supposition is supported by clinical observations that treatment with leukotriene receptor antagonists significantly improve asthma control when added to inhaled corticosteroid therapy. Moreover, the bronchodilator properties of the leukotriene receptor antagonists are additive with those of beta agonists. These data provide strong support for the use of leukotriene receptor antagonists for treating asthma. PMID

  2. Effects of the estrogen receptor antagonist fulvestrant on F344 rat prolactinoma models.

    Science.gov (United States)

    Cao, Lei; Gao, Hua; Gui, Songbai; Bai, Giwei; Lu, Runchun; Wang, Fei; Zhang, Yazhuo

    2014-02-01

    The relationship between estrogen and prolactinoma is well documented. But the anti-tumor effects of a pure estrogen receptor antagonist fulvestrant on prolactinomas, especially in vivo, and the possible mechanisms are still unclear. Therefore, the aim of this study was to evaluate the effects of fulvestrant and the involvement of the Wnt signaling pathway on rat prolactinoma models. Forty female F344 rat prolactinoma models were established by subcutaneous administration of 10 mg 17β-estradiol for 6 weeks. Rats were intramuscularly injected with fulvestrant (0, 0.5, 3, 20, 40 mg/kg), and tumor size, weight and serum prolactin (PRL) levels were evaluated before and after fulvestrant treatment at 3, 7 and 14 days. Expression of estrogen receptor α (ERα), β-catenin and Wnt inhibitory factor-1 (WIF-1) in prolactinomas was measured using quantitative PCR and western blotting, and methylation of the WIF-1 promoter was investigated using pyrosequencing. Tumor size, weight and serum PRL levels were inhibited in dose-dependent and time-dependent manners after fulvestrant treatments. β-catenin expression was downregulated but WIF-1 expression was upregulated following fulvestrant treatment. The methylation of the CpG site of the WIF-1 promoter was negatively correlated to the expression of WIF-1. In addition, the anti-cell proliferation of fulvestrant on GH3 cells was partly disrupted by Wnt signaling pathway agonist SB 216763. In conclusion, fulvestrant inhibited tumor proliferation and PRL secretion of prolactinomas via ERα, and the Wnt signaling pathway was involved in this anti-tumor effect. Therefore, fulvestrant may be a potential new drug for prolactinomas. PMID:24407733

  3. Physical exercise versus fluoxetine: antagonistic effects on cortical spreading depression in Wistar rats.

    Science.gov (United States)

    Mirelle Costa Monteiro, Heloísa; Lima Barreto-Silva, Nathália; Elizabete Dos Santos, Gracyelle; de Santana Santos, Amanda; Séfora Bezerra Sousa, Mariana; Amâncio-Dos-Santos, Ângela

    2015-09-01

    The antidepressant fluoxetine and physical exercise exert similar effects on the serotoninergic system by increasing brain serotonin availability, and both show antagonistic action on cortical excitability. Here we provide the first assessment of the interaction of the two together on cortical spreading depression (CSD) in young adult rats. Wistar rats (40-60 days of life) received fluoxetine (10mg/kg/d, orogastrically) or an equivalent volume of water. Half of the animals from each condition were assigned to perform physical exercise in a treadmill, and the other half formed the sedentary (non-treadmill) control groups. Body parameters (Lee index and thoracic and abdominal circumferences) and the velocity of CSD propagation were investigated. Fluoxetine+exercise animals had less weight gain (78.68±3.19g) than either the fluoxetine-only (93.34±4.77g) or exercise-only group (97.04±3.48g), but body parameters did not differ among them. The velocity of CSD propagation was reduced in the fluoxetine-only and exercise-only groups compared to sedentary water controls (3.24±0.39mm/min). For the fluoxetine+exercise group, CSD velocity values were significantly lower (2.92±0.22mm/min) than for fluoxetine only (3.03±0.35mm/min); however, they were similar to values for the exercise-only group (2.96±0.23mm/min). These findings confirm the similar effects of fluoxetine and exercise and suggest a greater effect of physical exercise in reducing brain excitability. PMID:26004534

  4. Inhibitory Effect of Serotonin Antagonist on Leukocyte-Endothelial Interactions In Vivo and In Vitro.

    Directory of Open Access Journals (Sweden)

    Hiroshi Kataoka

    Full Text Available Although 5-HT2A serotonergic antagonists have been used to treat vascular disease in patients with diabetes mellitus or obesity, their effects on leukocyte-endothelial interactions have not been fully investigated. In this study, we assessed the effects of sarpogrelate hydrochloride (SRPO, a 5-HT2A receptor inverse agonist, on leukocyte-endothelial cell interactions in obesity both in vivo and in vitro.In the in vivo experiment, C57BL/6 mice were fed a high-fat high-fructose diet (HFFD, comprising 20% fat and 30% fructose, with or without intraperitoneal injection of 5 mg/kg/day SRPO for 4 weeks. The body weight, visceral fat weight, and serum monocyte chemoattractant protein-1 levels in the mice increased significantly with the HFFD, but these effects were prevented by chronic injections of SRPO. Intravital microscopy of the femoral artery detected significant leukocyte-endothelial interactions after treatment with HFFD, but these leukocyte-endothelial interactions were reduced in the mice injected with SRPO. In the in vitro experiment, pre-incubation of activated human umbilical vein endothelial cells (HUVECs with platelet-rich plasma (PRP induced THP-1 cell adhesion under physiological flow conditions, but the adhesion was reduced by pretreatment of PRP with SRPO. A fluorescent immunobinding assay showed that PRP induced significant upregulation of E-selectin in HUVECs, but this upregulation was reduced by pretreatment of PRP with SRPO. In other in vitro conditions, pre-incubation of THP-1 cells with phorbol 12-myristate 13-acetate increased the adhesion of THP-1 cells to activated HUVECs under rotational conditions, but this adhesion was reduced by pretreatment with SRPO. Western blotting analysis showed that protein kinase C α activation in THP-1 cells was inhibited by SRPO.Our findings indicated that SRPO inhibits vascular inflammation in obesity via inactivation of platelets and leukocytes, and improvement of obese.

  5. Effect of a D3 receptor antagonist on context-induced reinstatement of nicotine seeking.

    Science.gov (United States)

    Sabioni, Pamela; Di Ciano, Patricia; Le Foll, Bernard

    2016-01-01

    Despite the existence of several treatment options for smoking cessation, the rate of relapse after treatment is very high. We and others have proposed that targeting the dopamine D3 receptor (DRD3) may be a good strategy for treatment of nicotine dependence. In human participants, reintroduction to an environment previously associated with drug-taking may induce relapse. In animals, such phenomenon can be studied using the context-induced reinstatement paradigm. As the role of DRD3 in context-induced reinstatement of nicotine-seeking has not yet been explored, we investigated the effects of different doses of the selective DRD3 antagonist SB-277011-A on this reinstatement. Sprague-Dawley adult rats were first trained to self-administer nicotine and subsequently underwent extinction in a second context for 5-7 days. We evaluated the effect of 1, 3 or 10mg/kg of SB-277011-A administered prior to the reintroduction to the training context. We used two different designs: 1) a between-subjects design with a unique reinstatement test; and 2) a counterbalanced within-subjects design, with 4 reinstatement tests. Our findings indicate that, in the within-subjects design, the magnitude of responding induced by the context-induced reinstatement of nicotine seeking was robust during the first reinstatement test, but significantly decreased with repeated testing. SB-277011-A (10mg/kg) blocked context-induced reinstatement of nicotine-seeking at first exposure to the context (between-subjects design), but not after repeated context exposure which produced weaker reinstatement over days. Our results support a role for DRD3 mediating context-induced reinstatement of nicotine seeking, but these effects may not be sustained over time. Further studies should explore this in human participants for validation. PMID:26279138

  6. Anticaries effect of dentifrices with calcium citrate and sodium trimetaphosphate

    Science.gov (United States)

    DELBEM, Alberto Carlos Botazzo; BERGAMASCHI, Maurício; RODRIGUES, Eliana; SASSAKI, Kikue Takebayashi; VIEIRA, Ana Elisa de Mello; MISSEL, Emilene Macario Coimbra

    2012-01-01

    Because of the growing concerns regarding fluoride ingestion by young children and dental fluorosis, it is necessary to develop new dentifrices. Objective The aim of this study was to evaluate the effect of dentifrices with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel demineralization. Material and Methods Enamel blocks (n=70), previously selected through surface hardness analysis, were submitted to daily treatment with dentifrices diluted in artificial saliva and to a pH-cycling model. The fluoride concentration in dentifrices was 0, 250, 450, 550, 1,000 and 1,100 µg F/g. CrestTM was used as a positive control (1,100 mg F/g). Cacit (0.25%) and TMP (0.25%) were added to dentifrices with 450 and 1,000 µg F/g. Surface hardness was measured again and integrated loss of subsurface hardness and fluoride concentration in enamel were calculated. Parametric and correlation tests were used to determine difference (p0.05). Conclusions Dentifrices with 450 and 1,000 µg F/g, Cacit and TMP were as effective as a gold standard one. PMID:22437685

  7. Anticaries effect of dentifrices with calcium citrate and sodium trimetaphosphate

    Directory of Open Access Journals (Sweden)

    Alberto Carlos Botazzo Delbem

    2012-02-01

    Full Text Available Because of the growing concerns regarding fluoride ingestion by young children and dental fluorosis, it is necessary to develop new dentifrices. OBJECTIVE: The aim of this study was to evaluate the effect of dentifrices with calcium citrate (Cacit and sodium trimetaphosphate (TMP on enamel demineralization. MATERIAL AND METHODS: Enamel blocks (n=70, previously selected through surface hardness analysis, were submitted to daily treatment with dentifrices diluted in artificial saliva and to a pH-cycling model. The fluoride concentration in dentifrices was 0, 250, 450, 550, 1,000 and 1,100 µg F/g. CrestTM was used as a positive control (1,100 mg F/g. Cacit (0.25% and TMP (0.25% were added to dentifrices with 450 and 1,000 µg F/g. Surface hardness was measured again and integrated loss of subsurface hardness and fluoride concentration in enamel were calculated. Parametric and correlation tests were used to determine difference (p0.05. CONCLUSIONS: Dentifrices with 450 and 1,000 µg F/g, Cacit and TMP were as effective as a gold standard one.

  8. Effects of Sigma Anti-bonding Molecule Calcium Carbonate on bone turnover and calcium balance in ovariectomized rats.

    Science.gov (United States)

    Choi, So-Young; Park, Dongsun; Yang, Goeun; Lee, Sun Hee; Bae, Dae Kwon; Hwang, Seock-Yeon; Lee, Paul K; Kim, Yun-Bae; Kim, Ill-Hwa; Kang, Hyun-Gu

    2011-12-01

    This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

  9. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2001-01-01

    Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability, ...... antagonists are additive with those of beta agonists. These data provide strong support for the use of leukotriene receptor antagonists for treating asthma.......Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability...... ciliary motility, which may hinder mucociliary clearance. Asthmatic patients demonstrate increased production of cysteinyl leukotrienes during naturally occurring asthma and acute asthma attacks as well as after allergen and exercise challenge. The leukotriene receptor antagonists montelukast, zafirlukast...

  10. Effects of extremely low frequency electromagnetic fields on intracellular calcium transients in cardiomyocytes.

    Science.gov (United States)

    Wei, Jinhong; Sun, Junqing; Xu, Hao; Shi, Liang; Sun, Lijun; Zhang, Jianbao

    2015-03-01

    Calcium transients play an essential role in cardiomyocytes and electromagnetic fields (EMF) and affect intracellular calcium levels in many types of cells. Effects of EMF on intracellular calcium transients in cardiomyocytes are not well studied. The aim of this study was to assess whether extremely low frequency electromagnetic fields (ELF-EMF) could affect intracellular calcium transients in cardiomyocytes. Cardiomyocytes isolated from neonatal Sprague-Dawley rats were exposed to rectangular-wave pulsed ELF-EMF at four different frequencies (15 Hz, 50 Hz, 75 Hz and 100 Hz) and at a flux density of 2 mT. Intracellular calcium concentration ([Ca(2+)]i) was measured using Fura-2/AM and spectrofluorometry. Perfusion of cardiomyocytes with a high concentration of caffeine (10 mM) was carried out to verify the function of the cardiac Na(+)/Ca(2+) exchanger (NCX) and the activity of sarco(endo)-plasmic reticulum Ca(2+)-ATPase (SERCA2a). The results showed that ELF-EMF enhanced the activities of NCX and SERCA2a, increased [Ca(2+)]i baseline level and frequency of calcium transients in cardiomyocytes and decreased the amplitude of calcium transients and calcium level in sarcoplasmic reticulum. These results indicated that ELF-EMF can regulate calcium-associated activities in cardiomyocytes. PMID:24499289

  11. Physico-chemical properties and toxic effect of fruit-ripening agent calcium carbide

    Directory of Open Access Journals (Sweden)

    Mohammad Asif

    2012-01-01

    Full Text Available Ripening is the final stage of the maturation process, when the fruit changes color, softens and develops the flavor, texture and aroma that constitute optimum eating quality. This study was conducted to discuss the use of unsatisfactory calcium carbide to ripen fruits for domestic markets as well as their toxic effects on human health. The commonly used ripening agents are calcium carbide, acetylene, ethylene, propylene, ethrel (2-chloroethyl phosphonic acid, glycol, ethanol and some other agents. The calcium carbide is one of the most commonly used ripening agent for fruits, while other calcium salts like calcium ammonium nitrate, calcium chloride and calcium sulfate are used to delay fruit ripening agents for local fruit industries. The use of calcium carbide is being discouraged worldwide, due to associated health hazards. Calcium carbide treatment of food is extremely hazardous because it contains traces of arsenic and phosphorous, and once dissolved in water, it produces acetylene gas. Arsenic, phosphorous and acetylene gas may affect the different body organs and causes various health problems like headache, dizziness, mood disturbances, sleepiness, mental confusion, memory loss, cerebral edema, seizures and prolonged hypoxia.

  12. Effects of Exogenous Calcium on Some Postharvest Characteristics of Cut Gladiolus

    Institute of Scientific and Technical Information of China (English)

    BAI Ji-gang; XU Pei-lei; ZONG Cheng-shun; WANG Cai-yun

    2009-01-01

    In order to apply calcium to the vase solutions of cut gladiolus (Gladiolus hybridus), the vase life and some physiological characteristics were studied in this article. A gladiolus cultivar, Mascagni, was chosen for experiments, and its cut flowers were held into solutions, which contained calcium acetate, ethylene glycol bis-amino tetmacetate (EGTA), and water,respectively. The effects of calcium were probed by measuring the ornamental quality of cut gladiolus and the physiological characteristics such as ealmodulin (CAM), abscisic acid (ABA), gibberellins (GA), zeatin (ZRs), endogenous calcium,malondialdehyde (MDA), and soluble sugar in florets. In a solution of 2 mmol L-1 calcium acetate, the opening rate of cut gladiolus was higher than that of control, and the vase life and ornamental value of flowers were better than that in control and other treatments of calcium acetate. Thus, the solution of 2 mmol L-1 calcium acetate has the best effect on the fresh keeping of cut gladiolus. In petals and bracts of cut gladiolus, the contents of CaM and GA and the ratios of GA/ABA and ZRs/ABA were higher in treatment of 2 mmol L-1 calcium acetate than that in control, while the contents of ABA and MDA were lower. Compared with the control, the solution of 2 mmol L-1 calcium acetate increased the endogenous calcium contents, and decreased the MDA contents, and alleviated the effects of EGTA on CaM, GA, GA/ABA, and ZRs/ABA. It made the soluble sugar content higher in petals than the control, but lower in bracts. Thus, the solution of 2 mmol L-1calcium acetate not only stabilizes the membrane structure of cut gladiolus, but also activates CaM. It thereby controls the endogenous hormone levels, and transports soluble sugar into petals, and increases the vase life of the flower.

  13. Effect of inhibitors on macroscopical oxidation kinetics of calcium sulfite

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yi; WANG Li-dong; WANG Xiao-ming; LI Qiang-wei; XU Pei-yao

    2005-01-01

    In the presence of inhibitors, the macroscopical oxidation kinetics of calcium sulfite, the main byproduct in wet limestone scrubbing, was studied for the first time by adding different inhibitors and varying pH, concentration of calcium sulfite, oxygen partial pressure, concentration of inhibitors and temperature. The mathematical model about the general oxidation reaction was established,which was controlled by three steps involving dissolution of calcium sulfite, mass transfer of oxygen and chemical reaction in the solution.It was concluded that the general reaction was controlled by mass transfer of oxygen under uncatalyzed conditions, while it was controlled by dissolution of calcium sulfite after adding three kinds of inhibitors. Thus, the theory was provided for investigating the mechanism and oxidation kinetics of sulfite. The beneficial references were also supplied for design of oxidation technics in the wet limestone scrubbing.

  14. High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats.

    Science.gov (United States)

    Charoenphandhu, Narattaphol; Tudpor, Kukiat; Thongchote, Kanogwun; Saengamnart, Wasana; Puntheeranurak, Supaporn; Krishnamra, Nateetip

    2007-02-01

    High physiological prolactin induced positive calcium balance by stimulating intestinal calcium absorption, reducing renal calcium excretion, and increasing bone calcium deposition in female rats. Although prolactin-induced increase in trabecular bone calcium deposition was absent after ovariectomy, its effects on cortical bones were still controversial. The present investigation, therefore, aimed to study the effect of in vivo long-term high physiological prolactin induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin injection on cortical bones in ovariectomized rats. Since the presence of prolactin receptors (PRLR) in different bones of normal adult rats has not been reported, we first determined mRNA expression of both short- and long-form PRLRs at the cortical sites (tibia and femur) and trabecular sites (calvaria and vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both PRLR isoforms with predominant long form at all sites. However, high prolactin levels induced by AP transplantation in normal rats did not have any effect on the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium deposition, and total calcium content in tibia and femur of adult ovariectomized rats. AP transplantation also had no effect on the cortical total calcium content in adult ovariectomized rats. Because previous work showed that the effects of prolactin were age dependent and could be modulated by high-calcium diet, interactions between prolactin and these two parameters were investigated. The results demonstrated that 2.0% wt/wt high-calcium diet significantly increased the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats but decreased the tibial total calcium content in 22-wk-old adult rats. As for the vertebrae, the total calcium contents in both young and adult rats were not changed by high-calcium

  15. Long-lasting effect of NMDA receptor antagonist memantine on ethanol-cue association and relapse.

    Science.gov (United States)

    Vengeliene, Valentina; Olevska, Anastasia; Spanagel, Rainer

    2015-12-01

    It is well known that the glutamatergic system plays a crucial role in alcohol addiction and especially in relapse-like behaviour. However, results of clinical studies on compounds that influence the activity of the glutamatergic system have been disappointing so far. The aim of our study was to establish treatment conditions under which the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine may produce more reliable treatment effect with respect to alcohol relapse-like behaviour. For this purpose, male Wistar rats were trained to associate several discrete stimuli with ethanol delivery. Thereafter, half of the animals received a brief memory reactivation session followed by two administrations of 20 mg/kg of memantine, while the other half received the same treatment without memory reactivation. Afterwards, a cue-induced ethanol-seeking behaviour test was performed followed by repeated extinction sessions and a reacquisition test. Our data show that administration of memantine reduced responding on the ethanol-associated lever in a cue-induced ethanol-seeking test. This reduction did not depend on whether or not a memory reactivation session was introduced prior to memantine administration. Following extinction, however, reacquisition of ethanol self-administration was only impaired in the group where memantine was given after a short memory reactivation session, showing that this schedule of drug administration produced a long-lasting disruption of the association between the conditioned stimuli and the delivery of ethanol. In conclusion, we show that memantine disrupted the drug-cue association, which consequently interfered with relapse-like behaviour supporting the possibility that memantine is a treatment option for alcoholism. Our data supports the possibility that memantine is a treatment option for alcoholism. However, the effectiveness of this drug seems to lie in its ability to disrupt conditioned behaviours and should be given in conjunction

  16. Synergetic and Antagonistic Effects of Cadmium on Adsorption of Atrazine on Surficial Sediments

    Institute of Scientific and Technical Information of China (English)

    LI Yu; GAO Qian; WANG Xiao-li; DONG De-ming; WANG Ao

    2009-01-01

    Co-contamination of atrazine(AT) and cadmium(Cd) on the surficial sediments(SSs) and natural suface coating samples(NSCSs) was investigated via thermodynamic adsorption experiments.The results show that surface coatings have a stronger ability to adsorb AT owing to their higher active components compared with surficial sediments.Synergetic and antagonistic effects of Cd on the adsorption of AT were observed.Cd at a lower concentration(≤4.0 mg/L) in the solid/liquid phase enhanced AT adsorption onto the surficiai sediments(surface coatings),while the adsorption of AT would be inhibited at a Cd concentration of more than 8.0 mg/L:AT coordinates strongly to Cd,and AT-Cd complexes seem to be more strongly adsorbed on sediments than AT alone,and at the adsorption of AT can take place on the sites where Cd has been previously adsorbed and Cd acts as a bridge for the interaction between sediments and AT.With the increase of Cd concentration,the superfluous Cd may hold much more adsorption sites and thus inhibits the adsorption of AT.Meanwhile,the effects of co-existed AT on Cd adsorption on SSs(NSCSs)were insignificant since Cd has a stronger competitive ability to be absorbed on SSs(NSCSs).The present study could be useful in predicting interactions of the metal ions with herbicides and potentially aid the design of remediation strategies for contaminated sediments and groundwater.

  17. Therapeutic effect of the NMDA antagonist MK-801 on low-level laser induced retinal injury

    Science.gov (United States)

    Yan, W.-H.; Wu, J.; Chen, P.; Dou, J.-T.; Pan, C.-Y.; Mu, Y.-M.; Lu, J.-M.

    2009-03-01

    The aim of this article was to explore the mechanism of injury in rat retina after constant low-level helium-neon (He-Ne) laser exposure and therapeutic effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on laser-induced retinal injury. He-Ne laser lesions were created in the central retina of adult Wistar Kyoto rats and were followed immediately by intraperitoneal injection of MK-801 (2 mg/kg) or saline, macroscopical and microscopical lesion were observed by funduscope and light microscope. Ultrastructural changes of the degenerating cells were examined by electron microscopy. Photoreceptor apoptosis was evaluated by TdT-mediated dUTP nick end-labeling (TUNEL). mRNA levels were measured by in situ hybridization and NMDA receptor expression was determined by immunohistochemistry. Laser induced damage was histologically quantified by image-analysis morphometry. Electroretinograms (ERGs) were recorded at different time point after the cessation of exposure to constant irradiation. There was no visible bleeding, exudation or necrosis under funduscope. TUNEL and electron microscopy showed photoreceptor apoptosis after irradiation. MK-801-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after exposure to laser. In situ hybridization (ISH) showed that the NMDAR mRNA level of MK-801-treated rats decreased in the inner plexiform layer 6 h after the cessation of exposure to constant irradiation when compared with that of saline-treated rats. So did Immunohistochemistry (IHC). Electroretinogram showed that b-wave amplitudes of MK-801-treated group were higher than that of saline-treated group after laser exposure. These findings suggest that Low level laser may cause the retinal pathological changes under given conditions. High expression of NMDAR is one of the possible mechanisms causing experimental retinal laser injury of rats. MK-801 exhibits the therapeutic effect due to promote the

  18. Calcium channel blocking activity of fruits of callistemon citrinus

    International Nuclear Information System (INIS)

    Callistemon citrinus is a plant of family myrtaceae that has a great medicinal importance. Traditional uses of the aerial parts of Callistemon citrinus in ethnic tribal communities are in practice, and very little are known about its importance on scientific grounds. Therefore, the crude methanolic extract of fruits of Callistemon citrinus (C.c) was screened for possible spasmolytic activity on isolated rabbit's jejunum preparations. The extract produced a relaxing effect on spontaneous contraction of rabbit's jejunum. Explaining the mode of action, the extract produced a dose dependent relaxant effect and shifted the calcium response curves to the rightward (EC50 +- SEM = -2.05 +- 0.05 vs. control EC50 +- SEM = -2.5 +- 0.05). The effect of extract was comparable with the effect of verapamil, a standard calcium channel blocker and therefore, the plant specie could be a potential target for isolation of calcium antagonist(s). (author)

  19. Effects of Pranlukast, a Cysteinyl Leukotriene Antagonist, on Bronchial Responsiveness to Methacholine in Aspirin-Intolerant Asthmatics Treated with Corticosteroids

    OpenAIRE

    ISHIOKA Shinichi; Hozawa, Soichiro; Haruta, Yoshinori; Maeda, Akihiro; Tamagawa, Kotaro; Watanabe, Tetsuya; Hiyama, Keiko; Yamakido, Michio

    2000-01-01

    Cysteinyl leukotrienes (cysLTs) are considered to be the most important mediator involved in the pathogenesis of aspirin-intolerant asthma (AIA). However, the role of cysLTs in the baseline condition of the pathophysiology of AIA when not exposed to non-steroidal antiinflammatory drugs (NSAIDs) as well as that in the pathophysiology of aspirin-tolerant asthma remains to be elucidated. Therefore, we evaluated the effect of pranlukast, a potent, selective cysLT receptor antagonist, on bronchial...

  20. Therapeutic effects of TNF-α antagonist etanercept and methotrexate on antigen-induced arthritis of the temporomandibular joint

    OpenAIRE

    Rafayelyan, Smbat

    2015-01-01

    Background: Juvenile idiopathic arthritis (JIA) of the temporomandibular joint (TMJ) can cause severe growth disturbances of the craniomandibular system. Antigen-induced arthritis (AIA) of the rabbit TMJ is simulating the inflammatory process of the TMJ in JIA. In the first two studies of the present thesis the effect of a systemic administration of the tumor necrosis factor-alpha (TNF-α) antagonist etanercept and methotrexate (MTX) on AIA in young rabbits should be investigate...

  1. Antagonist effect of Interleukin 1 receptor on normal thymopoiesis and thymus toxicity of 5-azacytidine in mouse

    OpenAIRE

    Yu, Hongjing; Wu, Mingyuan; Wen, Bin; Sun, Ningyun; Xiang, Di; Zhang, Jing; Zhu, Shunying; Weng, Shunyan; Yu, Yan; HAN, WEI

    2016-01-01

    Thymopoiesis is essential and significant for development and maintenance of the robust and healthy immune system. The acute suppression of thymopoiesis induced by 5-Azacytidine (5-Aza) is an intractable clinical problem complicating chemotherapy. Interleukin 1 receptor antagonist (IL-1Ra) is a cytokine that competitively blocks binding of interleukin 1 (IL-1) to its receptor. This study aims to investigate the effects of the IL-1Ra on the thymus toxicity of 5-Aza in mouse. In this study, we ...

  2. The Effect of Antagonistic Pleiotropy on the Estimation of the Average Coefficient of Dominance of Deleterious Mutations

    OpenAIRE

    Fernández, B.; García-Dorado, A; Caballero, A.

    2005-01-01

    We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for n...

  3. Effects of Astragalus membranaceus with supplemental calcium on bone mineral density and bone metabolism in calcium-deficient ovariectomized rats.

    Science.gov (United States)

    Kang, Se-Chan; Kim, Hee Jung; Kim, Mi-Hyun

    2013-01-01

    It has been reported that Astragalus membranaceus, an Asian traditional herb, has an estrogenic effect in vitro. To examine the possible role of A. membranaceus extract with supplemental calcium (Ca) on bone status in calcium-deficient (LCa) ovariectomized (OVX) rats, a total of 48 female rats were divided into six groups: (1) normal control, (2) sham operation with LCa (sham-LCa), (3) OVX with LCa (OVX-LCa), (4) A. membranaceus supplementation with OVX-LCa (OVX-MLCa), (5) Ca supplementation with OVX (OVX-Ca), and (6) A. membranaceus and Ca supplementation with OVX (OVX-MCa). A. membranaceus ethanol extract (500 mg/kg BW) and/or Ca (800 mg/kg BW) were administered orally for 8 weeks along with a Ca-deficient diet. Results revealed that Ca supplementation with or without A. membranaceus extract significantly improved bone mineral density, biomechanical strength, and ash weight of the femur and tibia in OVX rats. High Ca with A. membranaceus combination supplementation significantly increased the ash weight of the femur and tibia and decreased urinary Ca excretion compared with supplementation of Ca alone. Uterine weight was not changed by A. membranaceus administration in OVX rats. These results suggest that A. membranaceus extract combined with supplemental Ca may be more protective against the Ca loss of bone than A. membranaceus or supplementation of Ca alone in calcium-insufficient postmenopausal women.

  4. The effects of angiotensin II receptor antagonist (candesartan on rat renal vascular resistance

    Directory of Open Access Journals (Sweden)

    Supatraviwat, J

    2004-05-01

    Full Text Available The present study aimed to investigate the action of angiotensin II (AII on renal perfusion pressure and renal vascular resistance using noncompetitive AT1-receptor antagonist (candesartan or CV 11974. Experiments were performed in isolated kidney of adult male Wistar rats. Kreb's Henseleit solution was perfused into the renal artery at the rate of 3.5 ml/min. This flow rate was designed in order to maintain renal perfusion pressure between 80-120 mm Hg. Dose-response relationship between perfusion flow rate and AII concentration were studied. Renal perfusion pressure in response to 1, 10 and 100 nM AII were increased from basal perfusion pressure of 94±8 mm Hg to 127±6, 157±12 and 190±16 mm Hg, respectively. Administration of perfusate containing 11.4 μM candesartan for 30 min had no effect on the basal perfusion pressure. However, this significantly reduced renal perfusion pressure in the presence of AII (1, 10 and 100 nM by 39%, 47% and 61%, (n=7, P<0.05 respectively. At the basal perfusion pressure, calculated renal vascular resistance was 27±2 mm Hg · min · ml-1. However, the vascular resistance were found to be 41±1, 45±2 and 47±2 mm Hg · min · ml-1 when 1, 10 and 100 nM AII were added. Moreover, this dose of candesartan also showed a significant decrease in renal vascular resistance at the corresponding doses of AII by 38%, 48% and 43%, (n=7, P<0.05 respectively. The higher dose of candesartan (22.7 μM completely inhibited the action of 1, 10 and 100 nM AII on renal vasoconstriction. These results may indicate that the action of AII on renal vascular resistance is via AT1-receptor, at least in rat isolated perfusion kidney.

  5. The effect of antagonistic pleiotropy on the estimation of the average coefficient of dominance of deleterious mutations.

    Science.gov (United States)

    Fernández, B; García-Dorado, A; Caballero, A

    2005-12-01

    We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for nonpleiotropic and pleiotropic mutations in populations at the mutation-selection-drift balance. From these distributions we build homozygous and heterozygous chromosomes and assess the behavior of the estimators of dominance. A very small number of deleterious mutations with antagonistic pleiotropy produces substantial increases on the estimate of the average degree of dominance of mutations affecting the fitness component under study. For example, estimates are increased three- to fivefold when 2% of segregating loci are over-dominant for fitness. In contrast, strengthening pleiotropy, where pleiotropic effects are assumed to be also deleterious, has little effect on the estimates of the average degree of dominance, supporting previous results. The antagonistic pleiotropy model considered, applied under mutational parameters described in the literature, produces patterns for the distribution of chromosomal viabilities, levels of genetic variance, and homozygous mutation load generally consistent with those observed empirically for viability in Drosophila melanogaster. PMID:16118193

  6. Effect of strength enhancement of soil treated with environment-friendly calcium carbonate powder.

    Science.gov (United States)

    Park, Kyungho; Jun, Sangju; Kim, Daehyeon

    2014-01-01

    This study aims to investigate the effects of the strength improvement of soft ground (sand) by producing calcium carbonate powder through microbial reactions. To analyze the cementation effect of calcium carbonate produced through microbial reaction for different weight ratios, four different types of specimens (untreated, calcium carbonate, cement, and calcium carbonate + cement) with different weight ratios (2%, 4%, 6%, and 8%) were produced and cured for a period of 3 days, 7 days, 14 days, 21 days, and 28 days to test them. The uniaxial compression strength of specimens was measured, and the components in the specimen depending on the curing period were analyzed by means of XRD analysis. The result revealed that higher weight ratios and longer curing period contributed to increased strength of calcium carbonate, cement, and calcium carbonate + cement specimens. The calcium carbonate and the calcium carbonate + cement specimens in the same condition showed the tendency of decreased strength approximately 3 times and two times in comparison with the 8% cement specimens cured for 28 days, but the tendency of increased strength was approximately 4 times and 6 times in comparison with the untreated specimen. PMID:24688401

  7. I. Effects of a Dopamine Receptor Antagonist on Fathead Minnow, Pimephales promelas ,Reproduction

    Science.gov (United States)

    This study used a 21 d fathead minnow (Pimephales promelas) reproduction assay to test the hypothesis that exposure to the dopamine 2 receptor (D2R) antagonist, haloperidol, would impair fish reproduction. Additionally, a 96 h experiment with fathead minnows and zebrafish (Danio ...

  8. The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects

    DEFF Research Database (Denmark)

    Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C.;

    2015-01-01

    cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly...

  9. Extended studies on the effect of glutamate antagonists on ischemic CA-1 damage

    DEFF Research Database (Denmark)

    Diemer, Nils Henrik; Balchen, T; Bruhn, T;

    1996-01-01

    Glutamate receptors are numerous on the ischemia vulnerable CA-1 pyramidal cells. Postischemic use of the AMPA antagonist NBQX has shown up to 80% protection against cell death. Three aspects of this were studied: In the first study, male Wistar rats were given NBQX (30 mg/kg x 3) either 20 hours...

  10. No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

    DEFF Research Database (Denmark)

    Estrup, T M; Paulson, O B; Strandgaard, S

    2001-01-01

    Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral cir...

  11. The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.

    Science.gov (United States)

    Malik, Peter; Andersen, Maibritt B; Peacock, Linda

    2004-08-01

    Tardive dyskinesia (TD), a serious complication of antipsychotic dopamine (DA) antagonist treatment, has been hypothesised to develop due to a dominant DA D1 relative to DA D2 receptor function. Recent genetic and pharmacological studies implicate the DA D3 receptor in TD. The present study examined the role of the DA D3 receptor in relation to the DA D1/D2 imbalance hypothesis of TD in nonhuman primates. Eight Cebus monkeys displaying mild to severe TD due to previous chronic exposure to DA D2 antagonists were acutely injected with SKF 81297 (DA D1 agonist) 0.3 and 0.6 mg/kg, pramipexole (DA D3>D2 agonist) 0.025-0.1 mg/kg, CIS-8-OH-PBZI (DA D3 agonist) 5-10 mg/kg and SB-27701-A (DA D3 antagonist) 1-5 mg/kg and rated for oral dyskinesia. SKF 81297, 0.3 and 0.6 mg/kg, exacerbated TD. Pramipexole and CIS-8-OH-PBZI reduced SKF 81297-induced TD, while SB-27701-A had no effect. When administered alone, SB-27701-A increased TD relative to placebo, while pramipexole and CIS-8-OH-PBZI had no significant effect. Pramipexole did, however, ameliorate TD in those monkeys with severe TD. These results point towards a role of the DA D3 receptor in TD, but indicate that the DA D2 receptor may also play an essential role. PMID:15301939

  12. Calcium source (image)

    Science.gov (United States)

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  13. The effect of compressive loading magnitude on in situ chondrocyte calcium signaling.

    Science.gov (United States)

    Madden, Ryan M J; Han, Sang-Kuy; Herzog, Walter

    2015-01-01

    Chondrocyte metabolism is stimulated by deformation and is associated with structural changes in the cartilage extracellular matrix (ECM), suggesting that these cells are involved in maintaining tissue health and integrity. Calcium signaling is an initial step in chondrocyte mechanotransduction that has been linked to many cellular processes. Previous studies using isolated chondrocytes proposed loading magnitude as an important factor regulating this response. However, calcium signaling in the intact cartilage differs compared to isolated cells. The purpose of this study was to investigate the effect of loading magnitude on chondrocyte calcium signaling in intact cartilage. We hypothesized that the percentage of cells exhibiting at least one calcium signal increases with increasing load. Fully intact rabbit femoral condyle and patellar bone/cartilage samples were incubated in calcium-sensitive dyes and imaged continuously under compressive loads of 10-40 % strain. Calcium signaling was primarily associated with the dynamic loading phase and greatly increased beyond a threshold deformation of about 10 % nominal tissue strain. There was a trend toward more cells exhibiting calcium signaling as loading magnitude increased (p = 0.133). These results provide novel information toward identifying mechanisms underlying calcium-dependent signaling pathways related to cartilage homeostasis and possibly the onset and progression of osteoarthritis.

  14. Synthesis, structure, and frequency-doubling effect of calcium cyanurate.

    Science.gov (United States)

    Kalmutzki, Markus; Ströbele, Markus; Wackenhut, Frank; Meixner, Alfred J; Meyer, H-Jürgen

    2014-12-15

    Calcium cyanurate is synthesized by reacting calcium chloride with potassium cyanate following a solid-state reaction. The formation of the new compound Ca3(O3C3N3)2 (CCY), which occurs by the cyclotrimerization of cyanate ions, was examined thermoanalytically and the crystal structure was determined by single-crystal structure analysis. The structure of CCY is closely related to the structure of the well-known oxoborate β-BaB2O4 (BBO). Second harmonic generation (SHG) measurements on crystal powders show a higher SHG efficiency for CCY than for BBO by about one order of magnitude.

  15. Synthesis, structure, and frequency-doubling effect of calcium cyanurate.

    Science.gov (United States)

    Kalmutzki, Markus; Ströbele, Markus; Wackenhut, Frank; Meixner, Alfred J; Meyer, H-Jürgen

    2014-12-15

    Calcium cyanurate is synthesized by reacting calcium chloride with potassium cyanate following a solid-state reaction. The formation of the new compound Ca3(O3C3N3)2 (CCY), which occurs by the cyclotrimerization of cyanate ions, was examined thermoanalytically and the crystal structure was determined by single-crystal structure analysis. The structure of CCY is closely related to the structure of the well-known oxoborate β-BaB2O4 (BBO). Second harmonic generation (SHG) measurements on crystal powders show a higher SHG efficiency for CCY than for BBO by about one order of magnitude. PMID:25345390

  16. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength.

    Directory of Open Access Journals (Sweden)

    Emilie Louise Hansen

    Full Text Available Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy. Electroporation with calcium causes ATP (adenosine triphosphate depletion and cancer cell death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy.In three human cell lines--H69 (small-cell lung cancer, SW780 (bladder cancer, and U937 (leukaemia, viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99 μs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to quantify the cell-killing efficacy in presence of calcium. Post-treatment intracellular ATP was measured in H69 and SW780 cells. Post-treatment intracellular ATP was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells.Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field decrease in intracellular ATP (p<0.05 and reduced viability. The 50% effective cell kill was found at 3.71 kV/cm (H69 and 3.28 kV/cm (SW780, reduced to 1.40 and 1.15 kV/cm (respectively with 1 mM calcium (lower EC50 for higher calcium concentrations. Quinacrine fluorescence intensity of calcium-electroporated U937 cells was one third lower than in controls (p<0.0001.Calcium electroporation dose-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field.This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials.

  17. Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Wu, Wei; Saunders, Richard C; Mishkin, Mortimer; Turchi, Janita

    2012-07-01

    Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells. PMID:22561485

  18. Antagonist properties of Conus parius peptides on N-methyl-D-aspartate receptors and their effects on CREB signaling.

    Directory of Open Access Journals (Sweden)

    Shailaja Kunda

    Full Text Available Three members of a family of small neurotoxic peptides from the venom of Conus parius, conantokins (Con Pr1, Pr2, and Pr3, function as antagonists of N-methyl-D-aspartate receptors (NMDAR. We report structural characterizations of these synthetic peptides, and also demonstrate their antagonistic properties toward ion flow through NMDAR ion channels in primary neurons. ConPr1 and ConPr2 displayed moderate increases in α-helicity after addition of Mg(2+. Native apo-ConPr3 possessed an α-helical conformation, and the helicity increased only slightly on addition of Mg(2+. Additionally, these peptides diminished NMDA/Gly-mediated currents and intracellular Ca(2+ (iCa(2+ influx in mature rat primary hippocampal neurons. Electrophysiological data showed that these peptides displayed slower antagonistic properties toward the NMDAR than conantokins from other species of cone snails, e.g., ConT and ConG. Furthermore, to demonstrate selectivity of the C. parius-derived conantokins towards specific NMDAR subunits, cortical neurons from GluN2A(-/- and GluN2B(-/- mice were utilized. Robust inhibition of NMDAR-mediated stimulation in GluN2A(-/--derived mouse neurons, as compared to those isolated from GluN2B(-/--mouse brains, was observed, suggesting a greater selectivity of these antagonists towards the GluN2B subunit. These C. parius conantokins mildly inhibited NMDAR-induced phosphorylation of CREB at Ser(133, suggesting that the peptides modulated iCa(2+ entry and, thereby, activation of CREB, a transcription factor that is required for maintaining long-term synaptic activity. Our data mechanistically show that while these peptides effectively antagonize NMDAR-directed current and iCa(2+ influx, receptor-coupled CREB signaling is maintained. The consequence of sustained CREB signaling is improved neuronal plasticity and survival during neuropathologies.

  19. Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects

    Directory of Open Access Journals (Sweden)

    Esposito Emanuela

    2011-04-01

    Full Text Available Abstract Background Permanent functional deficits following spinal cord injury (SCI arise both from mechanical injury and from secondary tissue reactions involving inflammation. Enhanced release of adenosine and glutamate soon after SCI represents a component in the sequelae that may be responsible for resulting functional deficits. The role of adenosine A2A receptor in central ischemia/trauma is still to be elucidated. In our previous studies we have demonstrated that the adenosine A2A receptor-selective agonist CGS21680, systemically administered after SCI, protects from tissue damage, locomotor dysfunction and different inflammatory readouts. In this work we studied the effect of the adenosine A2A receptor antagonist SCH58261, systemically administered after SCI, on the same parameters. We investigated the hypothesis that the main action mechanism of agonists and antagonists is at peripheral or central sites. Methods Spinal trauma was induced by extradural compression of SC exposed via a four-level T5-T8 laminectomy in mouse. Three drug-dosing protocols were utilized: a short-term systemic administration by intraperitoneal injection, a chronic administration via osmotic minipump, and direct injection into the spinal cord. Results SCH58261, systemically administered (0.01 mg/kg intraperitoneal. 1, 6 and 10 hours after SCI, reduced demyelination and levels of TNF-α, Fas-L, PAR, Bax expression and activation of JNK mitogen-activated protein kinase (MAPK 24 hours after SCI. Chronic SCH58261 administration, by mini-osmotic pump delivery for 10 days, improved the neurological deficit up to 10 days after SCI. Adenosine A2A receptors are physiologically expressed in the spinal cord by astrocytes, microglia and oligodendrocytes. Soon after SCI (24 hours, these receptors showed enhanced expression in neurons. Both the A2A agonist and antagonist, administered intraperitoneally, reduced expression of the A2A receptor, ruling out the possibility that the

  20. Fouling control mechanisms of demineralized water backwash: Reduction of charge screening and calcium bridging effects

    KAUST Repository

    Li, Sheng

    2011-12-01

    This paper investigates the impact of the ionic environment on the charge of colloidal natural organic matter (NOM) and ultrafiltration (UF) membranes (charge screening effect) and the calcium adsorption/bridging on new and fouled membranes (calcium bridging effect) by measuring the zeta potentials of membranes and colloidal NOM. Fouling experiments were conducted with natural water to determine whether the reduction of the charge screening effect and/or calcium bridging effect by backwashing with demineralized water can explain the observed reduction in fouling. Results show that the charge of both membranes and NOM, as measured by the zeta potential, became more negative at a lower pH and a lower concentration of electrolytes, in particular, divalent electrolytes. In addition, calcium also adsorbed onto the membranes, and consequently bridged colloidal NOM and membranes via binding with functional groups. The charge screening effect could be eliminated by flushing NOM and membranes with demineralized water, since a cation-free environment was established. However, only a limited amount of the calcium bridging connection was removed with demineralized water backwashes, so the calcium bridging effect mostly could not be eliminated. As demineralized water backwash was found to be effective in fouling control, it can be concluded that the reduction of the charge screening is the dominant mechanism for this. © 2011 Elsevier Ltd.

  1. Effects of a newly developed potent orexin-2 receptor-selective antagonist, compound 1 m, on sleep/wakefulness states in mice

    OpenAIRE

    Keishi eEtori; Yuki eSaito; Natsuko eTsujino; Takeshi eSakurai

    2014-01-01

    Orexins (also known as hypocretins), which are hypothalamic neuropeptides, play critical roles in the regulation of sleep/wakefulness states by activating two G-protein coupled receptors (GPCRs), orexin 1 (OX1R) and orexin 2 receptors (OX2R). In order to know the difference between effects of OX2R-selective antagonists (2-SORA) and dual orexin receptor antagonists (DORA), and to understand the mechanisms underlying orexin-mediated regulation of sleep/wakefulness states, we examined the effect...

  2. The effect of phototherapy on urinary calcium excretion in term neonates

    OpenAIRE

    Afshin Safaei Asl; Marjaneh Zarkeshl; Abtin Heidarzadeh; Shohreh Maleknejad; Kaveh Hagikhani

    2016-01-01

    Phototherapy is the most common, most effective, and least dangerous treatment method for neonatal hyperbilirubinemia and is the treatment of the first choice for neonatal icterus. Hypocalcemia is one of the lesser-known complications of phototherapy. Some studies have shown a relationship between increased urinary calcium excretion and phototherapy-induced hypocalcemia. We aimed to assess the effect of phototherapy on urinary calcium excretion in term neonates. This before-after study was pe...

  3. Effects of modulation of calcium levels and calcium fluxes on ABA- induced gene expression in barley aleurone

    NARCIS (Netherlands)

    Meulen, R.M. van der; Visser, K.; Wang, M.

    1996-01-01

    We present data to elucidate the involvement of calcium ions in abscisic acid (ABA)-induced gene expression. Modulation of external calcium concentrations was able to affect ABA-induced specific RAB gene expression. At a constant ABA level with increasing extracellular calcium level, an increasing R

  4. Effects of histamine H(1) receptor antagonists on depressive-like behavior in diabetic mice.

    Science.gov (United States)

    Hirano, Shoko; Miyata, Shigeo; Onodera, Kenji; Kamei, Junzo

    2006-02-01

    We previously reported that streptozotocin-induced diabetic mice showed depressive-like behavior in the tail suspension test. It is well known that the central histaminergic system regulates many physiological functions including emotional behaviors. In this study, we examined the role of the central histaminergic system in the diabetes-induced depressive-like behavior in the mouse tail suspension test. The histamine contents in the hypothalamus were significantly higher in diabetic mice than in non-diabetic mice. The histamine H(1) receptor antagonist chlorpheniramine (1-10 mg/kg, s.c.) dose-dependently and significantly reduced the duration of immobility in both non-diabetic and diabetic mice. In contrast, the selective histamine H(1) receptor antagonists epinastine (0.03-0.3 microg/mouse, i.c.v.) and cetirizine (0.01-0.1 microg/mouse, i.c.v.) dose-dependently and significantly suppressed the duration of immobility in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity was not affected by histamine H(1) receptor antagonists in either non-diabetic or diabetic mice. In addition, the number and affinity of histamine H(1) receptors in the frontal cortex were not affected by diabetes. In conclusion, we suggest that the altered neuronal system mediated by the activation of histamine H(1) receptors is involved, at least in part, in the depressive-like behavior seen in diabetic mice.

  5. Effect of the IL-1 Receptor Antagonist Kineret® on Disease Phenotype in mdx Mice.

    Science.gov (United States)

    Benny Klimek, Margaret E; Sali, Arpana; Rayavarapu, Sree; Van der Meulen, Jack H; Nagaraju, Kanneboyina

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by mutations in the dystrophin gene. The pathology of DMD manifests in patients with progressive muscle weakness, loss of ambulation and ultimately death. One of the characteristics of DMD is muscle inflammation, and dystrophin-deficient skeletal muscles produce higher levels of the pro-inflammatory cytokine interleukin 1β (IL-1β) in response to toll like receptor (TLR) stimulation compared to controls; therefore, blocking the IL-1β pathway could improve the disease phenotype in mdx mice, a mouse model of DMD. Kineret® or IL-1Ra is a recombinant IL-1 receptor antagonist approved by the FDA for treating rheumatoid arthritis. To determine the efficacy of IL-1Ra in a DMD model, we administered subcutaneous injections of saline control or IL-1Ra (25 mg/kg/day) to mdx mice daily for 45 days beginning at 5 weeks of age. Functional and histological parameters were measured at the conclusion of the study. IL-1Ra only partially inhibited this signaling pathway in this study; however, there were still interesting observations to be noted. For example, although not significantly changed, splenocytes from the IL-1Ra-treated group secreted less IL-1β after LPS stimulation compared to control mice indicating a blunted response and incomplete inhibition of the pathway (37% decrease). In addition, normalized forelimb grip strength was significantly increased in IL-1Ra-treated mice. There were no changes in EDL muscle-specific force measurements, histological parameters, or motor coordination assessments in the dystrophic mice after IL-1Ra treatment. There was a significant 27% decrease in the movement time and total distance traveled by the IL-1Ra treated mice, correlating with previous studies examining effects of IL-1 on behavior. Our studies indicate partial blocking of IL-1β with IL-1Ra significantly altered only a few behavioral and strength related disease parameters; however, treatment with

  6. Effect of the IL-1 Receptor Antagonist Kineret® on Disease Phenotype in mdx Mice.

    Directory of Open Access Journals (Sweden)

    Margaret E Benny Klimek

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked muscle disease caused by mutations in the dystrophin gene. The pathology of DMD manifests in patients with progressive muscle weakness, loss of ambulation and ultimately death. One of the characteristics of DMD is muscle inflammation, and dystrophin-deficient skeletal muscles produce higher levels of the pro-inflammatory cytokine interleukin 1β (IL-1β in response to toll like receptor (TLR stimulation compared to controls; therefore, blocking the IL-1β pathway could improve the disease phenotype in mdx mice, a mouse model of DMD. Kineret® or IL-1Ra is a recombinant IL-1 receptor antagonist approved by the FDA for treating rheumatoid arthritis. To determine the efficacy of IL-1Ra in a DMD model, we administered subcutaneous injections of saline control or IL-1Ra (25 mg/kg/day to mdx mice daily for 45 days beginning at 5 weeks of age. Functional and histological parameters were measured at the conclusion of the study. IL-1Ra only partially inhibited this signaling pathway in this study; however, there were still interesting observations to be noted. For example, although not significantly changed, splenocytes from the IL-1Ra-treated group secreted less IL-1β after LPS stimulation compared to control mice indicating a blunted response and incomplete inhibition of the pathway (37% decrease. In addition, normalized forelimb grip strength was significantly increased in IL-1Ra-treated mice. There were no changes in EDL muscle-specific force measurements, histological parameters, or motor coordination assessments in the dystrophic mice after IL-1Ra treatment. There was a significant 27% decrease in the movement time and total distance traveled by the IL-1Ra treated mice, correlating with previous studies examining effects of IL-1 on behavior. Our studies indicate partial blocking of IL-1β with IL-1Ra significantly altered only a few behavioral and strength related disease parameters; however

  7. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

    Directory of Open Access Journals (Sweden)

    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  8. Effect of chitooligosaccharides on calcium bioavailability and bone strength in ovariectomized rats.

    Science.gov (United States)

    Jung, Won-Kyo; Moon, Sung-Hoon; Kim, Se-Kwon

    2006-01-25

    Chitosan polymer with deacetylation degree of 93% was hydrolyzed with an endo-type chitosanase (35,000 U/g protein) with substrate to enzyme ratio of 1 to 1.5 for 18 h in a batch reactor, and then the resultant hydrolysates were fractionated into four different molecular weights using an ultrafiltration (UF) membrane reactor system. An in vitro study elucidated that four kinds of chitooligosaccharides (COSs) could efficiently inhibit the formation of insoluble calcium salts in the neutral pH. In vivo effects of COSs on Ca bioavailability were further studied in the osteoporosis modeling rats induced by ovariectomy and concurrent low calcium intake. During the experimental period corresponding to the menopause with the osteoporosis disease, calcium retention was increased and bone turnover was decreased by COS IV supplementation in the ovariectomized (OVX) rats. After the low Ca diet, COS IV diet including both normal level of calcium and vitamin D significantly decreased calcium loss in feces and increased calcium retention compared to the control diet. The levels of femoral total calcium, bone mineral density (BMD), and femoral strength were also significantly increased by the COS IV diet in a similar level to those of CPP diet group. In the present study, the results proved the beneficial effects of low molecular chitooligosaccharide (COS IV) in preventing negative mineral balance.

  9. Antagonistic effects of a covalently dimerized insulin derivative on insulin receptors in 3T3-L1 adipocytes.

    OpenAIRE

    Weiland, M; Brandenburg, C; Brandenburg, D.; Joost, H. G.

    1990-01-01

    In the present study we describe the antagonistic effects of the covalently dimerized insulin derivative B29,B29'-suberoyl-insulin on insulin receptors in 3T3-L1 mouse cells. In differentiated 3T3-L1 adipocytes, the derivative fully inhibits binding of 125I-labeled insulin to its receptor with about the same affinity as unlabeled insulin. In contrast, the dimerized derivative only partially (approximately 20%) mimics insulin's effects on glucose transport and DNA synthesis in the absence of i...

  10. In vitro and in vivo protein phosphorylation in Avena sativa L. coleoptiles: effects of Ca2+, calmodulin antagonists, and auxin

    Science.gov (United States)

    Veluthambi, K.; Poovaiah, B. W.

    1986-01-01

    In vitro and in vivo protein phosphorylations in oat (Avena sativa L.) coleoptile segments were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by two-dimensional gel electrophoresis. In vitro phosphorylation of several polypeptides was distinctly promoted at 1 to 15 micromolar free Ca2+ concentrations. Ca2(+)-stimulated phosphorylation was markedly reduced by trifluoperazine, chlorpromazine, and naphthalene sulfonamide (W7). Two polypeptides were phosphorylated both under in vitro and in vivo conditions, but the patterns of phosphorylation of several other polypeptides were different under the two conditions indicating that the in vivo phosphorylation pattern of proteins is not truly reflected by in vitro phosphorylation studies. Trifluoperazine, W7, or ethylene glycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) + calcium ionophore A23187 treatments resulted in reduced levels of in vivo protein phosphorylation of both control and auxin-treated coleoptile segments. Analysis by two-dimensional electrophoresis following in vivo phosphorylation revealed auxin-dependent changes of certain polypeptides. A general inhibition of phosphorylation by calmodulin antagonists suggested that both control and auxin-treated coleoptiles exhibited Ca2+, and calmodulin-dependent protein phosphorylation in vivo.

  11. Calcium-regulated in vivo protein phosphorylation in Zea mays L. root tips

    Science.gov (United States)

    Raghothama, K. G.; Reddy, A. S.; Friedmann, M.; Poovaiah, B. W.

    1987-01-01

    Calcium dependent protein phosphorylation was studied in corn (Zea mays L.) root tips. Prior to in vivo protein phosphorylation experiments, the effect of calcium, ethyleneglycol-bis-(beta-aminoethyl ether)-N-N' -tetraacetic acid (EGTA) and calcium ionophore (A-23187) on phosphorus uptake was studied. Calcium increased phosphorus uptake, whereas EGTA and A-23187 decreased it. Consequently, phosphorus concentration in the media was adjusted so as to attain similar uptake in different treatments. Phosphoproteins were analyzed by two-dimensional gel electrophoresis. Distinct changes in phosphorylation were observed following altered calcium levels. Calcium depletion in root tips with EGTA and A-23187 decreased protein phosphorylation. However, replenishment of calcium following EGTA and ionophore pretreatment enhanced phosphorylation of proteins. Preloading of the root tips with 32P in the presence of EGTA and A-23187 followed by a ten minute calcium treatment, resulted in increased phosphorylation indicating the involvement of calcium, calcium and calmodulin-dependent kinases. Calmodulin antagonist W-7 was effective in inhibiting calcium-promoted phosphorylation. These studies suggest a physiological role for calcium-dependent phosphorylation in calcium-mediated processes in plants.

  12. Effects of Dietary Calcium on Body Weight, Carcass Fat Content and Adipocyte Size in Male Rats

    Directory of Open Access Journals (Sweden)

    J Malekzadeh

    2006-07-01

    Full Text Available Introduction & Objective: Calcium is a micronutrient and now receiving much attention for its doubtful effects on weight and body fatness. A few mechanisms has been suggested for calcium effects on body fatness and the most emphasized one is the reducing of lipolysis and increasing lipogenesis via reducing parathyroid hormone levels. The present study is designed to evaluate the effects of nondairy dietary calcium on adipogenesis and adipocyte size in male Sprague dawley rats. Materials & Methods: This experimental study was done from November to September of 2005 at Tehran school of health, nutrition department. 48 male Spragu-Dawley rats from Damgostar Company were used in three randomly selected groups. The rats were fed low (0.2% W/W, usual (0.5% W/W and high (1.2% W/W dietary calcium based on AIN-93M purified diet. Rats were housed in 12 hours light-dark cycle, 22-25°C room temperature with free access to their respective diets. At the end of the experiment, rats were decapitated and carcass fat content, carcass ash content and mean adipocyte size in testis, peritoneal and subcutaneous fat pads were compared in three groups. The SPSS 11.5 was used as statistical software, running analysis of variance for comparing the effects. Results: weight gain, carcass fat content and adipocyte size, in groups were not significantly different, while serum parathyroid hormone concentrations in high calcium group was significantly lower than low calcium group (p<0.05 and insignificantly lower than usual calcium group [12.36, 23.57 and 42.2 pg/dl respectively]. Serum concentrations of 25-hydroxy cholecalciferol were also insignificantly lower in high calcium group. Conclusion: Our findings suggested that physiological concentration of dietary calcium is not effective on weight gain, body fatness and adipocyte size. Relatively equal fat content beside significant difference in serum parathyroid hormone levels is against the parathyroid theory of calcium

  13. Clinical effect of calcium hydroxide paste combined with triple antibiotic paste on root canal disinfection

    Directory of Open Access Journals (Sweden)

    Chen QU

    2014-03-01

    Full Text Available Objective To compare the efficacy in disinfection and pain control of calcium hydroxide paste and triple antibiotic paste (ornidazole, ciprofloxacin and minocycline used individually or jointly for root canal disinfection. Methods Two hundred and thirty-five patients with chronic apical periodontitis (235 teeth were involved in the present study and divided into 2 groups: fistula group (n=118 and no fistula group (n=117. Each group was then randomly divided into 4 subgroups: calcium hydroxide paste group, triple antibiotic paste group, calcium hydroxide + triple antibiotic paste group, and camphor phenol group. After regular root canal preparation, root canals of patients in 4 groups were filled with tiny paper ends impregnated with fore 4 different drugs respectively. Visual analogue scales (VAS of pain were given to the patients with a guide for filling the scale. One week later, both the data of the scales and the effects of root canal disinfection were recorded and analyzed. Results Seven days after treatment, the clinical efficacy of calcium hydroxide paste, triple antibiotic paste and calcium hydroxide + triple antibiotic paste was similar (P>0.05 either in fistula group or in no fistula group, but all better than that of camphor phenol (P<0.05. VAS score analysis showed that, at least on the first 3 days after sealing medicine in the root canal, calcium hydroxide + triple antibiotic paste achieved better result of pain control than the other three groups (P<0.05 no matter with or without fistula. Conclusions  Calcium hydroxide paste, triple antibiotic paste, calcium hydroxide + triple antibiotic paste are effective in treatment of chronic apical periodontitis whether with or without fistula. However, the combined use of calcium hydroxide and three antibiotic pastes is better for controlling the pain after root canal preparation than other treatments, which is therefore worthy of clinical application. DOI: 10.11855/j.issn.0577-7402.2014.02.12

  14. Effect of a peripheral and a central acting opioid antagonist on the testicular response to stress in rats.

    Science.gov (United States)

    Akinbami, M A; Taylor, M F; Collins, D C; Mann, D R

    1994-04-01

    The possible involvement of opioid receptors in mediating the inhibitory effects of immobilization stress on testicular steroidogenesis was determined in adult male rats. Unstressed controls and animals exposed to 3 h of immobilization stress were injected subcutaneously with either vehicle or 1 or 10 mg/kg body weight (BW) of naloxone or naltrexone methobromide (NMB; an opioid receptor antagonist that does not cross the blood-brain barrier) at the beginning of and at 1.5 h of the stress period. Animals were sacrificed at 2 h (30 min after the second injection of antagonist) or 3 h (90 min after the second injection of antagonist) of stress. Plasma LH was not affected by stress, but 30 min after naloxone (1 or 10 mg/kg BW) injection, LH was elevated in both control and stressed rats above levels in vehicle-injected animals. By 90 min after naloxone injection, plasma LH had declined to levels comparable to those in vehicle-injected animals. NMB had no effect on plasma LH concentrations in either control or stressed rats. Three hours of stress reduced plasma testosterone (T) levels by 60% in vehicle-injected animals. This effect of stress on plasma T levels was antagonized by the 10 mg/kg BW dose of naloxone and 1 or 10 mg/kg BW of NMB. The ability of naloxone to reverse the effect of stress on plasma T levels was likely related to its ability to stimulate LH secretion, but NMB normalized plasma T values in stressed animals without altering plasma LH concentrations. Only the highest dose of NMB increased plasma T levels in unstressed control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8202214

  15. Antimicrobial effect of calcium hydroxide as endo intracanal dressing on Streptococcus viridans

    Directory of Open Access Journals (Sweden)

    Nanik Zubaidah

    2008-03-01

    Full Text Available Calcium hydroxide had been used as the intra-canal dressing in endodontic treatment due to its high alkaline and antimicrobial capacity. It can also dissolve the necrotic tissue, prevent dental root resorbtion and regenerate a new hard tissue. The aim of this study was to determine the concentration of calcium hydroxide which had the highest antimicrobial effect on Streptococcus viridans. Samples were divided into 5 groups; each group consisted of 8 samples with different concentration of calcium hydroxide. Group I: 50%, group II: 55, Group III: 60%, Group IV: 65%, Group V: 70%. The antimicrobial testing was performed using diffusion method against Streptococcus viridans. The result of susceptibility test was showed by the inhibition zone diameter which measured with caliper (in millimeter. We analyzed the data using One-Way ANOVA test with significant difference 0.05 and subsequently LSD test. The study showed that calcium hydroxide with concentration 60% has the highest antimicrobial effect.

  16. Effects of calcium channel on 3-morpholinosydnonimine-induced rat hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Quanzhong Chang; Shuling Zhang; Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Shining Cai

    2011-01-01

    Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus.The present study investigated the effects of the broad-spectrum calcium channel blocker CdC12 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis.The chloride channel blockers 4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulfonic acid (SITS) or 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) increased the survival rate of 3-morpholinosydnonimine (SIN-1)-treated neurons and suppressed SIN-1-induced neuronal apoptosis.The calcium channel blocker CdC12 did not increase the survival rate of neurons and did not affect SIN-1-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis.Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.

  17. Characterization of a silver-incorporated calcium phosphate film by RBS and its antimicrobial effects

    Energy Technology Data Exchange (ETDEWEB)

    Han, I-H [Institute of Physics and Applied Physics, and Atomic-Scale Surface Science Research Center, Yonsei University, Seou1 120-749 (Korea, Republic of); Lee, I-S [Institute of Physics and Applied Physics, and Atomic-Scale Surface Science Research Center, Yonsei University, Seou1 120-749 (Korea, Republic of); Song, J-H [Advanced Analysis Center, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Lee, M-H [Department of Medical Engineering, Yonsei University, Seoul 120-752 (Korea, Republic of); Park, J-C [Department of Medical Engineering, Yonsei University, Seoul 120-752 (Korea, Republic of); Lee, G-H [Korea Institute of Machinery and Materials, Chang-Won 641-010 (Korea, Republic of); Sun, X-D [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Chung, S-M [Implantium Research Center, Seoul 135-879 (Korea, Republic of)

    2007-09-15

    A thin calcium phosphate film was synthesized on both commercially pure Ti and Si wafers by electron beam evaporation of hydroxyapatite as an evaporant with simultaneous Ar ion beam bombardments. Silver was introduced into an ion-beam-assisted deposition of a calcium phosphate thin film for antimicrobial effect. The amount of incorporated silver ions was controlled by immersing calcium-phosphate-coated samples in different AgNO{sub 3} concentrations, and Rutherford backscattering spectrometry (RBS) was employed to measure the amounts of substituted silver. The higher concentration of silver in the calcium phosphate film was more effective in reducing the bacteria of Escherichia coli ATCC 8739 and Streptococcus mutans OMZ 65 on contact with respect to controls.

  18. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille;

    2012-01-01

    Electroporation of cells with short, high-voltage pulses causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating ions and molecules. In this study, we illustrate how electroporation with isotonic calcium can achieve highly effective cancer cell kill...... in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely due to a combination of increased cellular use of ATP......, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment...

  19. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P;

    1994-01-01

    Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral...... chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S)-phaclofen was...... inactive in this binding assay (IC50 > 1000 microM). (-)-(R)-Phaclofen (200 microM) was equipotent with (RS)-phaclofen (400 microM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 microM) was inactive. The structural similarity of the agonist (R)-baclofen...

  20. LIFE-SPANNING BEHAVIORAL AND ADRENAL DYSFUNCTION INDUCED BY PRENATAL HYPOXIA IN THE RAT IS PREVENTED BY THE CALCIUM-ANTAGONIST NIMODIPINE

    NARCIS (Netherlands)

    NYAKAS, C; BUWALDA, B; MARKEL, E; KORTE, SM; LUITEN, PGM

    1994-01-01

    The long-term behavioural effects of prenatal chronic anaemic hypoxia were investigated in young (5 months old), late adult (19 months) and aged Wistar rats (23 - 26 months). Sodium nitrite (2 g/l) offered in the drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In

  1. Effect of calcium ionophore on unfertilized oocytes after ICSI cycles

    OpenAIRE

    Maryam Eftekhar; Farnaz Mohammadian; Fariba Yousefnejad; Parisa Khani; Abbas Aflatoonian

    2012-01-01

    Background: Fertilization failure is one of the most problems in assisted reproduction technology (ART). Objective: The aim of this study was the evaluation of oocytes activation by addition of calcium ionophore in unfertilized oocytes in ICSI cycles. Materials and Methods: This study was done on 15 ICSI cycles (stimulated with standard long protocol). Mature retrieved oocytes with normal morphology that had no evidence of fertilization 24 hours after ICSI were included in the study. The oocy...

  2. Effect of calcium ionophore on unfertilized oocytes after ICSI cycles

    Directory of Open Access Journals (Sweden)

    Maryam Eftekhar

    2012-01-01

    Full Text Available Background: Fertilization failure is one of the most problems in assisted reproduction technology (ART. Objective: The aim of this study was the evaluation of oocytes activation by addition of calcium ionophore in unfertilized oocytes in ICSI cycles. Materials and Methods: This study was done on 15 ICSI cycles (stimulated with standard long protocol. Mature retrieved oocytes with normal morphology that had no evidence of fertilization 24 hours after ICSI were included in the study. The oocytes with fertilization and unfertilized oocytes with degeneration were excluded from the study. The unfertilized oocytes were washed with GIVF medium and were transferred to GIVF medium that contained 5 μmol of calcium ionophore and were incubated for 10 minutes. Then again oocytes were washed with GIVF medium and consequently were transferred to GIVF medium and were incubated at 37°C in 6% CO2. After 18 hours, the oocytes were examined and activated oocytes were defined with observation of at least one pronucleus or cleaved oocytes. Results: After ovarian stimulation and oocytes retrieval, 175 mature oocytes were obtained and injection of sperm was done for all of them. 114 of 175 oocytes (66% showed evidence of fertilization after 24 hours. A total of 61 oocytes (34% showed no evidence of fertilization and 10 oocytes were degenerated and were excluded from the study. Only 51 unfertilized oocytes with normal morphology were selected and were exposed to calcium ionophore. 37 (72.5% of treated oocytes were fertilized (2PN and 32 (62.7% of them showed evidence of cleavage. 6 (11.8% embryos had good quality. Conclusion: According to our results, oocytes activation with calcium ionophore had an acceptable fertilization rate, however high quality embryos remained low. We propose future studies to evaluate embryo quality.

  3. Electrophysiological effects of Ca antagonists, tetrodotoxin, [Ca]o and [Na]o on myocardium of hibernating chipmunks: possible involvement of Na-Ca exchange mechanism.

    OpenAIRE

    Kondo, N

    1987-01-01

    The electrophysiological performance of myocardium of hibernating chipmunks was investigated in the presence of Ca antagonists and tetrodotoxin, and the effects of high [Ca]o and low [Na]o were examined. The action potential of the preparations was characterized by the low amplitude of the plateau phase (APp). Ca antagonists, nifedipine (10(-6) M) and nitrendipine (2 X 10(-6) M), did not significantly inhibit this APp or the contraction. These nifedipine-insensitive electromechanical response...

  4. Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease

    Directory of Open Access Journals (Sweden)

    Li-Ping Wang

    2016-05-01

    Full Text Available Background/Aims: By inducing severe endothelial impairment, hypertension and diabetes are two leading causes of morbidity and mortality. Hypertensive patients with concomitant diabetes must take both antihypertensive and hypoglycaemic medications, for which there is a lack of experimental and clinical guidelines. This study aimed to examine the interaction between these two types of medication on the endothelial cell function. Methods: The effect of antihypertensive (nifedipine and irbesartan and anti-diabetic (metformin and glibenclamide/glimepiride drugs on human umbilical vein cells (HUVECs function was examined using a modified Boyden chamber assay. The intracellular NO and O2- levels of HUVECs were detected through flow cytometry. Results: Our findings showed that nifedipine/sulphonylurea monotherapy significantly attenuated high glucose-induced (33 mM HUVECs migration incapacity, while combination therapy of nifedipine and glibenclamide/glimepiride showed no protective effect. Both nifedipine/metformin monotherapy and combined therapy significantly mitigated the migration incapacity induced by high glucose in HUVECs. Combined with either metformin or sulphonylureas, irbesartan therapy was able to attenuate the high glucose-induced migration incapacity of HUVECs. Nifedipine monotherapy decreased the O2- levels and increased the NO levels in in vitro-cultured HUVECs treated with high glucose. However, the combination therapy of nifedipine and glibenclamide increased the O2- levels and decreased the NO levels compared to the nifedipine monotherapeutic group. Conclusion: The nifedipine and glibenclamide/glimepiride combination exerted a mutual antagonistic effect on the protection from high glucose-induced impairment in endothelial cells, which might be partially attributed to the increased O2- level and decreased NO level. These results imply that calcium channel blockers + sulphonylurea combination therapy warrants further attention in

  5. Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs.

    Science.gov (United States)

    Appel, Nathan M; Li, Shou-Hua; Holmes, Tyson H; Acri, Jane B

    2015-09-01

    The chronic and relapsing nature of addiction presents unique challenges for ensuring the safety of a potential medication. A patient may use cocaine, for example, while taking the medication or take more medication than prescribed. Thus, a potential medication must be safe and not exacerbate the effects of cocaine. Multiple published studies support antagonism of brain dopamine D3 receptor function as a potential mechanism of action for an anti-addiction medication. Dopamine D3 receptors are widely distributed outside the central nervous system, however; for example, dopamine D3 receptors in the kidneys are implicated in regulating blood pressure. The selective dopamine D3 receptor antagonist GSK598809 [1-(2-fluoro-4-trifluoromethyl-phenyl)-3-{3-[4-methyl-5-(4-methyl-oxazol-5-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-propyl}-3-aza-bicyclo[3.1.0]hexane] has been proposed as a medication to treat cocaine and other substance use disorders. The US Food and Drug Administration has established guidelines recommending safety studies to investigate potential undesirable pharmacodynamic effects of a substance in relation to exposure in the therapeutic range and above. Hence, we assessed the interaction between this selective dopamine D3 receptor antagonist and cocaine on hemodynamics and cardiac function in freely-moving, telemetered dogs before conducting a clinical trial. GSK598809 increased the hemodynamic effect of cocaine in this model. Thus, the increase in blood pressure after intravenous cocaine was greater in animals that had been pretreated with GSK598809 compared with vehicle. This finding suggests that GSK598809 in particular, and perhaps dopamine D3 receptor antagonists as a class, may produce unacceptable cardiovascular risks as medications to treat cocaine use disorder. PMID:26177654

  6. CGP 35348, a new GABAB antagonist, prevents antinociception and muscle-relaxant effect induced by baclofen.

    OpenAIRE

    Malcangio, M.; Ghelardini, C.; Giotti, A.; Malmberg-Aiello, P.; Bartolini, A.

    1991-01-01

    1. CGP 35348, a new GABAB antagonist, was examined on antinociception induced by (+/-)-baclofen by use of the hot plate and writhing tests in mice and the paw pressure test in rats. CGP 35348 was also studied in mice on (+/-)-baclofen-induced impairment of rota-rod performance. 2. CGP 35348, injected either i.p. (60-100 mg kg-1 in mouse) or intracerebroventricularly (i.c.v.) (0.5-2.5 micrograms per mouse; 25 micrograms per rat) prevented (+/-)-baclofen-induced antinociception. 3. CGP 35348 di...

  7. The effect of dietary calcium and phosphorus supplementation in zeolite A treated dry cows on periparturient calcium and phosphorus homeostasis

    DEFF Research Database (Denmark)

    Thilsing, Trine; Larsen, T.; Jørgensen, Rolf Jess;

    2007-01-01

    Previous studies have proved the possibility of preventing parturient hypocalcaemia by zeolite A supplementation during the dry period, and a recent in vitro study has indicated a marked calcium (Ca) as well as phosphorus (P) binding effect of zeolite A in rumen fluid solutions. Because...... of the connection between the Ca and P homeostatic systems, the preventive effect against parturient hypocalcaemia may arise from zeolite induced decreased availability of dietary Ca as well as P. In the present study, the expected Ca and P binding capacity was challenged by feeding high and low levels of dietary...... Ca and/or P to zeolite A treated dry cows. Twenty-one pregnant dry cows were assigned to four experimental groups receiving a dry cow ration unsupplemented or supplemented with extra Ca and/or P. During the last 2 weeks of the dry period all cows additionally received 600 g of zeolite A per day...

  8. Effects of taurine supplementation on bone mineral density in ovariectomized rats fed calcium deficient diet.

    Science.gov (United States)

    Choi, Mi-Ja

    2009-01-01

    Taurine supplementation has been shown to have a beneficial effect on femur bone mineral content in ovariectomized rats. It therefore seemed desirable to find out whether the beneficial effect of taurine on ovariectomized rats fed calcium deficient diet could also be reproduced. Forty female Sprague-Dawley rats were divided into two groups. One group was OVX and the other group received sham operation (SHAM), and received either control diet or a taurine supplemented diet for 6 weeks. All rats were fed on calcium deficient diet (AIN-93: 50% level of calcium) and deionized water. Bone mineral density (BMD) and bone mineral content (BMC) were measured in spine and femur. The serum and urine concentrations of calcium and phosphorus were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Urinary calcium and phosphorus excretion, osteocalcin in blood and cross link value were not significantly different among the groups. Within the OVX group, the taurine supplemented group had not higher femur bone mineral content than the control group. This study established the need for a study on the taurine effect on bone with different calcium levels.

  9. DNA protective effect of ginseng and the antagonistic effect of Chinese turnip: A supplementation study

    Science.gov (United States)

    Szeto, Yim Tong; Wong, Kam Shing; Han, Andrea; Pak, Sok Cheon; Kalle, Wouter

    2016-01-01

    Aim: The aim of this clinical study is to provide scientific evidence for supporting traditional Chinese application and usage to the patients. For this purpose, we tested the ability if Panax ginseng extract to lower oxidative damage to nuclear DNA in human lymphocytes by comparing the effect of cooked Chinese turnip on this effect. Materials and Methods: Seven healthy subjects (4 males and 3 females from 37 to 60 years) participated two occasions which were at least 2 weeks apart. About 2 mL of fasting blood sample for baseline measurement was taken on arrival. They were requested to ingest the content of 5 ginseng capsules in 200 mL water. The subject remained fasting for 2 h until the second blood sample taken. In the other occasion, the experiment was repeated except a piece of cooked turnip (10 g) was taken with the ginseng extract. The two occasions could be interchanged. Comet assay was performed on two specimens on the same day for the evaluation of lymphocytic DNA damage with or without oxidative stress. Results: For the group with ginseng supplementation, there was a significant decrease in comet score for hydrogen peroxide (H2O2) treatment over the 2-h period while no change in DNA damage for unstressed sample. For the group with ginseng together with turnip supplementation, there was no significant difference in comet score for both H2O2 treatment and phosphate-buffered saline treatment. Ginseng extract could reduce DNA damage mediated by H2O2 effectively, but this protection effect was antagonized by the ingestion of cooked turnip at the same time. Conclusion: In the current study, commercial ginseng extract was used for supplementing volunteers. Ginseng extract could protect DNA from oxidative stress in vivo while turnip diminished the protection.

  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. Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro

    Directory of Open Access Journals (Sweden)

    Elliott John T

    2005-02-01

    Full Text Available Abstract Background The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs, and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP, and a PAR-1 antagonist on human umbilical artery tone in vitro. Methods Human umbilical artery samples were obtained from 17 women at term. Arterial rings were suspended under physiologic conditions for isometric recording. The in vitro effects of thrombin (0.5 units/mL to 3 units/mL, PAR1-AP TFLLR-NH2 [10(-9 to 10(-6 M], and PAR-1 antagonist (N-trans cinnamoyl- p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Orn-NH2 [10(-9 M to 10(-5 M] on umbilical artery tone were measured. Results Both thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory effect on human umbilical artery resistance (P 0.05. Conclusion These findings highlight a potential role for thrombin and PAR-1 receptors in vascular regulation of feto-placental blood flow in normal pregnancy, and in association with the vascular lesions associated with IUGR and pre-eclampsia.

  12. Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular Myocyte of Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    林先明; 李真; 胡本容; 夏国瑾; 姚伟星; 向继洲

    2002-01-01

    Summary: The effects of Arecoline (Are) on calcium mobilization were investigated. In isolatedsingle ventricular myocyte of guinea pig, patch clamp whole cell recording techniques were used torecord the current of L-type calcium channel and cytosolic Ca2+ level ([Ca2+]i) labeled with fluo-rescence probe Fluo-3/AM was measured under a laser scanning confocal microscope. Results re-vealed that Are (3-100 μmol/L) could inhibit L-type calcium current in a concentration-depen-dent manner and the value of IC50 was 33. 73μmol/L (n= 5). In the absence of extracellular calci-um, the resting levels of [Ca2+]i was not affected by Are (n=6, P>0. 05), but pretreatmentwith Are (30 μmol/L) could significantly inhibit the [Ca2+]i elevation induced by caffeine (10mmol/L, n = 6, P < 0. 01). It was concluded that Are could inhibit not only calcium influxthrough L-type calcium channel but also calcium release from sarcoplasmic reticulum.

  13. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  14. Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced Nephropathy.

    Science.gov (United States)

    Min, Hye Sook; Cha, Jin Joo; Kim, Kitae; Kim, Jung Eun; Ghee, Jung Yeon; Kim, Hyunwook; Lee, Ji Eun; Han, Jee Young; Jeong, Lak Shin; Cha, Dae Ryong; Kang, Young Sun

    2016-09-01

    The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria. PMID:27510383

  15. Binding of [125I]iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    International Nuclear Information System (INIS)

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with [125I] iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for [125I] iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited [125I] iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes

  16. Calcium ion binding properties and the effect of phosphorylation on the intrinsically disordered Starmaker protein.

    Science.gov (United States)

    Wojtas, Magdalena; Hołubowicz, Rafał; Poznar, Monika; Maciejewska, Marta; Ożyhar, Andrzej; Dobryszycki, Piotr

    2015-10-27

    Starmaker (Stm) is an intrinsically disordered protein (IDP) involved in otolith biomineralization in Danio rerio. Stm controls calcium carbonate crystal formation in vivo and in vitro. Phosphorylation of Stm affects its biomineralization properties. This study examined the effects of calcium ions and phosphorylation on the structure of Stm. We have shown that CK2 kinase phosphorylates 25 or 26 residues in Stm. Furthermore, we have demonstrated that Stm's affinity for calcium binding is dependent on its phosphorylation state. Phosphorylated Stm (StmP) has an estimated 30 ± 1 calcium binding sites per protein molecule with a dissociation constant (KD) of 61 ± 4 μM, while the unphosphorylated protein has 28 ± 3 sites and a KD of 210 ± 22 μM. Calcium ion binding induces a compaction of the Stm molecule, causing a significant decrease in its hydrodynamic radius and the formation of a secondary structure. The screening effect of Na(+) ions on calcium binding was also observed. Analysis of the hydrodynamic properties of Stm and StmP showed that Stm and StmP molecules adopt the structure of native coil-like proteins. PMID:26445027

  17. Effect of pinaverium and other calcium channel blockers on contraction of isolated gastric antral smooth muscle cells caused by gastrointestinal hormones.

    Science.gov (United States)

    Bobo, M H; Magous, R; Christen, M O; Bali, J P

    1994-01-01

    Gastrointestinal hormones, gastrin, cholecystokinin (CCK), and motilin, are known to induce contraction of digestive smooth muscle cells from various species. In this paper, we studied the effect of calcium channel blockers, diltiazem, nicardipine, and pinaverium on the hormone-dependent contraction of smooth muscle cells isolated from rabbit antrum. Gastrin, CCK-8, and motilin caused dose-dependent contraction with EC-50 values in the physiological range (10-100 pM). This contractile effect was dependent upon extracellular calcium for gastrin and CCK-8 but not for motilin. When used alone, calcium channel blockers diltiazem, nicardipine, but not pinaverium, caused a weak but significant contraction of the cells. Pinaverium inhibited both gastrin- and CCK-8-induced contractions with IC-50 values of 1 nM and it was much less potent in the inhibition of motilin-induced contractions (IC-50 = 25 nM). The effect of pinaverium was equivalent to that of diltiazem in the inhibition of CCK-8- or gastrin-induced contractions. Both drugs were slightly more potent than nicardipine (IC-50 = 10 nM versus 1 nM for pineaverium and 5 nM for diltiazem). In contrast, diltiazem and pinaverium were less potent against motilin stimulation, diltiazem being 5 times more potent than pinaverium. In conclusion, it appears that since Ca2+ antagonists pinaverium, diltiazem and nicardipine inhibited contraction of smooth muscle cells stimulated by gastrointestinal hormones, "L-type" calcium channels of the plasma membrane might also be regulated through occupation of gastrin or CCK receptors. PMID:8201843

  18. Effects of coronal leakage on concentration of hydrogen ions and calcium release of several calcium hydroxide pastes over different periods of time

    Directory of Open Access Journals (Sweden)

    Mariana Pires Crespo

    2013-10-01

    Full Text Available PURPOSE: To evaluate the effects of coronal leakage on concentration of hydrogen ions (pH and calcium release of several calcium hydroxide pastes, over different periods of time. MATERIAL AND METHODS:  Fifty extracted human mandibular central incisors (n=10 were instrumented up to the F2 instrument and assigned to the following intracanal dressing: G1- Calen, G2- Calen with 0.4% chlorhexidine (CHX, G3- Calcium hydroxide with camphorated paramonochlorophenol (CPMC and glycerin, G4- Calen, but temporary filling material maintained during all test (positive control and G5- Root canal without intracanal dressing (negative control. All groups were immersed in distilled water for 7 days. In sequence, the temporary filling materials were removed, except in controls groups. All specimens were individually mounted on a specific device and only its root again immersed in distilled water. Concentration of hydrogen ions and calcium release by calcium hydroxide pastes in distilled water were evaluated in 24h, 7, 14 and 28 days. The results were submitted to ANOVA test (p = 0.05. After 28 days, root canals from experimental groups were examined in SEM. RESULTS: G1, G2, G3 and G4 presented similar pH values and calcium release and did not differ from each other (p>0.05, up to 7 days. After this time G1, G2 and G3 presented values lower values than G4 (p<0.05. In SEM analysis, calcium hydroxide residues were observed in all experimental groups. CONCLUSIONS: After 7 days, coronal leakage decreased the concentration of hydrogen ions and calcium ion release provided by all calcium hydroxide pastes.

  19. Effect of cholesterol liposomes on calcium mobilization in muscle cells from the rabbit sphincter of Oddi

    Institute of Scientific and Technical Information of China (English)

    Xin-Jiang Wang; Jing-Guo Wei; Chun-Mei Wang; Yao-Cheng Wang; Qiu-Zhen Wu; Jia-Kuan Xu; Xiang-Xin Yang

    2002-01-01

    AIM: To analyze the influence of cholesterol liposomes onthe Ca2 + mobilization of cultured muscle cells in the rabbitsphincter of Oddi.METHODS: New Zealand rabbit was sacrificed and thesphincter of Oddi (SO) segement wes obtained aseptically.The SO segment was cut into pieces and cultured in DMEMsolution. Then the smooth muscle cells were subcultured,and the 4th-7th passage cells were used for furtherinvestigation. The intracellular Ca2 + increase was measuredunder confocal microscope after the addition of 20mmol@ L- 1KCl, 10-7 mol @ L-1 acetylcholine and 10-7 mol @ L-1cholecystokinin, and different antagonists were added toanalyze the Ca2+ mobilization pathway. After the cells wereincubated with 1g@ L-1 cholesterol liposome (CL) (rnoarratio wes ~ 2: 1 ), the intracellular Ca2+ increase wasmeasured again to determine the effect of CL on cellularCa2+ mobilization.RESULTS: The resting cellular calcium concentration ofcultured SO cell was 108 ± nmol @ L-1 21 nmol @ L-1. Theintracellular Ca2 + increases induced by 20rmmol@ L- 1 KCl, 10-7mol@ L- 1 ACh and 10-7 mol@ L- 1 CCK were 183% ± 56%, 161%± 52% and 130% ± 43%, respectively. When theextracellular Ca2+ was eliminated by 2mmol@ L-1 EGTA and5μrnol@L-1 verapamil, the intracellular Ca2+ increasesinduced by KCl, ACh and CCK were 20% ± 14%, 82% ± 21%and 104% ± 23%, respectively. After the preincubation withheparin, the Ca2+ increases were 62% ± 23% and 23% ± 19%induced by ACh and CCK, as for preincubation withprocaine they were 72% ± 28% and 85% ± 37% induced byACh and CCK, respectively. Pretreatment with CL for 18h,the resting cellular Ca2 + concentration elevated to 152nmol@L-1 ± 26nmol@ L-1, however, the cellular Ca2+ increasepercentages in response to these agonists were 67% ± 32%,56% ± 33% and 34% ± 15%.CONCLUSION: KCl elicites the SO cellular Ca2+ increasedepends on influx of extracellular Ca2+ , ACh evoked the SOcelllular Ca2+ increase is through the mobilization ofintracellular Ca2+ pool and

  20. Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Hu XF

    2015-08-01

    Full Text Available Xiufen Hu,1,* Mohammad Ishraq Zafar,2,* Feng Gao2 1Department of Paediatrics, Tongji Hospital, 2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs and the influence of lipopolysaccharide (LPS, histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colony-stimulating factor (GM-CSF alone or with interleukin (IL-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL. We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA323–339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-γ production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4- than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days

  1. Effect of α{sub 7} nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    Energy Technology Data Exchange (ETDEWEB)

    Welch, Kevin D., E-mail: kevin.welch@ars.usda.gov [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Pfister, James A. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Lima, Flavia G. [Federal University of Goías, School of Veterinary Medicine, Goiânia, Goías (Brazil); Green, Benedict T.; Gardner, Dale R. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States)

    2013-02-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  2. Arctigenin exhibits relaxation effect on bronchus by affecting transmembrane flow of calcium.

    Science.gov (United States)

    Zhao, Zhenying; Yin, Yongqiang; Wang, Zengyong; Fang, Runping; Wu, Hong; Jiang, Min; Bai, Gang; Luo, Guo'an

    2013-12-01

    Arctigenin, a lignan extract from Arctium lappa (L.), exhibits anti-inflammation, antioxidation, vasodilator effects, etc. However, the effects of arctigenin on bronchus relaxation are not well investigated. This study aimed to investigate how arctigenin regulates bronchus tone and calcium ion (Ca(2+)) flow. Trachea strips of guinea pigs were prepared for testing the relaxation effect of arctigenin to acetylcholine, histamine, KCl, and CaCl2, respectively. Furthermore, L-type calcium channel currents were detected by patch-clamp, and intracellular Ca(2+) concentration was detected by confocal microscopy. The results showed that arctigenin exhibited relaxation effect on tracheae to different constrictors, and this was related to decreasing cytoplasmic Ca(2+) concentration by inhibiting Ca(2+) influx partly through L-type calcium channel as well as promoting Ca(2+) efflux. In summary, this study provides new insight into the mechanisms by which arctigenin exhibits relaxation effect on bronchus and suggests its potential use for airway disease therapy.

  3. Arctigenin exhibits relaxation effect on bronchus by affecting transmembrane flow of calcium.

    Science.gov (United States)

    Zhao, Zhenying; Yin, Yongqiang; Wang, Zengyong; Fang, Runping; Wu, Hong; Jiang, Min; Bai, Gang; Luo, Guo'an

    2013-12-01

    Arctigenin, a lignan extract from Arctium lappa (L.), exhibits anti-inflammation, antioxidation, vasodilator effects, etc. However, the effects of arctigenin on bronchus relaxation are not well investigated. This study aimed to investigate how arctigenin regulates bronchus tone and calcium ion (Ca(2+)) flow. Trachea strips of guinea pigs were prepared for testing the relaxation effect of arctigenin to acetylcholine, histamine, KCl, and CaCl2, respectively. Furthermore, L-type calcium channel currents were detected by patch-clamp, and intracellular Ca(2+) concentration was detected by confocal microscopy. The results showed that arctigenin exhibited relaxation effect on tracheae to different constrictors, and this was related to decreasing cytoplasmic Ca(2+) concentration by inhibiting Ca(2+) influx partly through L-type calcium channel as well as promoting Ca(2+) efflux. In summary, this study provides new insight into the mechanisms by which arctigenin exhibits relaxation effect on bronchus and suggests its potential use for airway disease therapy. PMID:24114345

  4. β受体阻滞剂分别联合血管紧张素受体拮抗剂和钙离子拮抗剂治疗江门地区中青年高血压的临床效果观察%Curative Effect of Beta-blockers Respectively Combination of Angiotensin Receptor Blockers and Calcium Antagonists in the Treatment of Young and Middle-Aged High Blood Pressure in Jiangmen

    Institute of Scientific and Technical Information of China (English)

    黄享贞; 钟洁霞

    2015-01-01

    目的:比较β受体阻滞剂分别联合血管紧张素受体拮抗剂(ARB)和钙离子拮抗剂(CCB)治疗江门地区中青年高血压的治疗效果。方法:选取2012年12月-2014年12月收治的江门地区中青年高血压患者300例,随机数字表法分为观察组和对照组各150例。观察组患者给予ARB联合β受体阻滞剂治疗,对照组给予CCB联合β受体阻滞剂治疗,观察两组治疗前后的血压、心率变化情况以及降压疗效和症状改变情况。结果:治疗8周后两组患者的血压、心率均较治疗前下降(P0.05),观察组心率下降较对照组明显,差异有统计学意义(P0.05),heart rate decline in treatment group and control group,the difference was statistically significant(P<0.05).In terms of hypertension treatment,observation group total effective rate was 94.67%,control group total effective rate was 82.00%, total effective rate of observation group was obviously higher than that of control group,the difference was statistically significant (P<0.05).In terms of symptom improvement,observation group total effective rate was 96.67%,control group total effective rate was 84.67%,total effective observation group was obviously higher than that of control group,the difference was statistically significant(P<0.05).Conclusion:The application of combined beta-blockers ARB can significantly reduce the diastolic and systolic blood pressure of patients,slow heart rate,and in terms of antihypertensive effects and symptoms improve curative effect is good,worthy of clinical promotion.

  5. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Gianlorenço, A.C.L.; Serafim, K.R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Canto-de-Souza, A. [Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattioli, R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-02-17

    This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

  6. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    International Nuclear Information System (INIS)

    This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM

  7. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice.

    Science.gov (United States)

    Gianlorenço, A C L; Serafim, K R; Canto-de-Souza, A; Mattioli, R

    2014-02-01

    This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

  8. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    Directory of Open Access Journals (Sweden)

    A.C.L. Gianlorenco

    2014-02-01

    Full Text Available This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM. The cerebellar vermis of male mice (Swiss albino was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2. Immediately after exposure to the EPM (T1, animals received a microinjection of saline (SAL or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2 under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE and spent less time in the open arms (%OAT in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

  9. Root-associated bacterial endophytes from Ralstonia solanacearum resistant and susceptible tomato cultivars and their pathogen antagonistic effects

    Directory of Open Access Journals (Sweden)

    Reshmi eUpreti

    2015-04-01

    Full Text Available This study was undertaken to assess if the root-associated native bacterial endophytes in tomato have any bearing in governing the host resistance to the wilt pathogen Ralstonia solanacearum. Internal colonization of roots by bacterial endophytes was confirmed through confocal imaging after SYTO-9 staining. Endophytes were isolated from surface-sterilized roots of 4-week old seedlings of known wilt resistant (R tomato cultivar Arka Abha and susceptible (S cv. Arka Vikas on nutrient agar after plating the tissue homogenate. Arka Abha displayed more diversity with nine distinct organisms while Arka Vikas showed five species with two common organisms (Pseudomonas oleovorans and Agrobacterium tumefaciens. Screening for general indicators of biocontrol potential showed more isolates from Arka Abha positive for siderophore, HCN and antibiotic biosynthesis than from Arka Vikas. Direct challenge against the pathogen indicated strong antagonism by three Arka Abha isolates (P. oleovorans, Pantoea ananatis and Enterobacter cloacae and moderate activity by three others, while just one isolate from Arka Vikas (P. oleovorans showed strong antagonism. Validation for the presence of bacterial endophytes on three R cultivars (Arka Alok, Arka Ananya, Arka Samrat showed 8-9 antagonistic bacteria in them in comparison with four species in the three S cultivars (Arka Ashish, Arka Meghali, Arka Saurabhav. Altogether 34 isolates belonging to five classes, 16 genera and 27 species with 23 of them exhibiting pathogen antagonism were isolated from the four R cultivars against 17 isolates under three classes, seven genera and 13 species from the four S cultivars with eight isolates displaying antagonistic effects. The prevalence of higher endophytic bacterial diversity and more antagonistic organisms associated with the seedling roots of resistant cultivars over susceptible genotypes suggest a possible role by the root-associated endophytes in natural defense against the

  10. ACTH Antagonists

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  11. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  12. ACTH Antagonists.

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing's disease and ectopic ACTH syndrome - especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia - as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  13. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists.

    Science.gov (United States)

    Harmon, Jennifer L; Wills, Lauren P; McOmish, Caitlin E; Demireva, Elena Y; Gingrich, Jay A; Beeson, Craig C; Schnellmann, Rick G

    2016-04-01

    In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP

  14. Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D2 and D3 Receptors

    Science.gov (United States)

    Wood, Martyn D.; Strange, Philip G.

    2016-01-01

    Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. PMID:27379794

  15. Effect of Calcium Sources and Particle Size on Performance and Eggshell Quality in Laying Hens

    Directory of Open Access Journals (Sweden)

    Arzu Erol Tunç

    2015-01-01

    Full Text Available An experiment was conducted to determine the effect of different combination calcium sources and particle size on performance and egg shell quality in layer hens. In the experiment, 198 brown laying hens at 44 week of age were randomly assigned into 11 treatments groups. The experimental diets consisted of different calcium sources (Fine limestone, large limestone, large oyster shell and large egg shell and their different combination. The experimental unit consisted of a groups of three hens, thus each treatment was replicated six times. Different calcium sources and particle size addition to the laying hens diet had no significantly effect on body weight gain, egg production, egg mass, feed intake, feed conversion ratio, egg specific gravity, egg shell weight, egg shell thickness and egg shell breaking strength but egg weight had significantly affected by the treatments. The significantly highest egg weight was found in laying hens fed with 50 % fine limestone and 50 % large limestone. Dietary different Ca sources had a significant effect on Ca, P and Mg as mineral contents of eggshell and tibia. In the present study, when dietary large calcium sources (limestone, oyster shell and egg shell had no effect on performance and eggshell quality parameters in laying hens. However, dietary containing at least 50 % large calcium sources had positive effect on mineral contents of tibia.

  16. Effect of calcium chloride addition on ice cream structure and quality.

    Science.gov (United States)

    Costa, F F; Resende, J V; Abreu, L R; Goff, H D

    2008-06-01

    The influence of calcium fortification by the addition of calcium chloride on quality parameters of ice cream based on physical properties was investigated, as was the effect of kappa-carrageenan at modifying the effects of this calcium fortification. Four ice cream mixes of conventional composition, with added kappa-carrageenan (0 or 0.025%) and added calcium chloride (0 or 4.4 g L(-1) = 40 mM of added Ca(2+)), were prepared. Modulated temperature-differential scanning calorimetry was used to investigate the effect of calcium chloride on the nucleation temperature, enthalpy of melting, and freezing point depression. The protein composition of 15.4% (wt/wt) reconstituted skim milk powder solutions with or without 4.4 g L(-1) added CaCl(2) and in the supernatant after ultracentrifugation was determined. Fat particle size distributions in ice cream were characterized by light scattering. Ice crystal sizes before and after temperature cycling were determined by cold-stage light microscopy. The results demonstrated that the addition of calcium chloride led to a substantial increase in ice crystal sizes and in fat partial coalescence, which were exacerbated by the addition of kappa-carrageenan. These results can be explained by the interaction between Ca(2+) ions and casein micelles, rather than any effects on freezing point depression. The calcium ions led to a more compact micelle, less serum beta-casein, and high fat destabilization, all of which would be expected to reduce macromolecular structure and volume occupancy in the unfrozen phase, which led to increased rates of ice recrystallization. PMID:18487638

  17. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan;

    2009-01-01

    OBJECTIVE: Interleukin (IL)-1 impairs insulin secretion and induces beta-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and beta......-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS: Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m(2) and were randomly assigned to receive 13 weeks of anakinra......, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in beta-cell function after anakinra withdrawal. Analysis was done by intention to treat. RESULTS: Thirty-nine weeks after anakinra withdrawal, the proinsulin...

  18. The effect of the benzodiazepine antagonist flumazenil on regional cerebral blood flow in human volunteers

    DEFF Research Database (Denmark)

    Wolf, J; Friberg, L; Jensen, J;

    1990-01-01

    The influence of the benzodiazepine antagonist flumazenil on regional cerebral blood flow (rCBF) was investigated in ten healthy, alert volunteers. The design was a randomized, placebo-controlled, double-blind, cross-over study. rCBF was measured by 133-Xe inhalation and single photon emission...... computerized tomography, SPECT, immediately before, and 5 and 35 min after intravenous injection of flumazenil 1.0 mg or placebo. In addition, mean arterial blood pressures or PaCO2, rCBF were analysed for changes in various regions of interest (RoI). No alterations were found either in the global CBF or in r......CBF in RoI after flumazenil injection. The results showed that a clinically active dose of flumazenil did not directly affect the cerebral circulation in the normal brain and indicated absence of significant intrinsic activity of the drug....

  19. Effects on anionic salts in a pre-partum dairy ration on calcium metabolism

    Directory of Open Access Journals (Sweden)

    C.J. Van Dijk

    2001-07-01

    Full Text Available The effects of anionic salts in the transition diet on serum and urine calcium at calving and on peripartal health, subsequent milk production and fertility performance were studied in a well-managed, high-producing Friesland dairy herd. Over a period of a year, approximately 21 days before the expected date of calving, 28 pre-partum heifers and 44 multiparous dry cows were randomly allocated within parity to 1 of 2 transition diets, designated control and experimental anionic diets. The anionic diet contained the same quantities of the basic transition ration fed to the control group as well as a standard anionic salt mixture containing 118 g NH4Cl, 36 g (NH42SO4 and 68 g MgSO4 (total 222 g per animal per day. This reduced the DCAD to -11.68 mEq/100 g dietary dry matter compared to +13.57 for the control diet. Blood and urine were randomly sampled from 7 to 8 animals within each category within 3 hours post-partum. Serum calcium (total and ionised and creatinine, urine calcium and creatinine and the fractional clearance of calcium were assessed. Relevant clinical, milk production, and fertility data were collected. The total serum calcium (2.07 versus 1.60 mmol/ , serum ionised calcium (1.12 vs 1.02 mmol/ , urine calcium (0.92 vs 0.10 mmol/ and the fractional clearance of calcium (1.88 vs 0.09 % were significantly higher (P <0.01 at calving for multiparous cows fed the anionic diet compared to those fed the control diet. In the primiparous cows there were no significant differences in serumcalcium levels. However, the urine calcium (1.07 vs 0.43 mmol/ and the fractional clearance of calcium was higher (1.75 vs 0.45 % in cows fed the anionic diet (P <0.05 and 0.01 respectively. These results illustrated that there were benefits, although no differences were demonstrated with respect to health, milk production or fertility. The supplementation of diets with anionic salts in the last 2-3 weeks before calving has the potential to significantly

  20. Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects on Tumor in Vitro

    Directory of Open Access Journals (Sweden)

    Qiao Zhang

    2016-08-01

    Full Text Available Endothelin-1 (ET-1 autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ETAR and endothelin B receptor (ETBR. Dysregulation of ETAR activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETAR and ETBR antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen, which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs, which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETAR.

  1. The adrenergic α2 antagonist atipamezole alters the behavioural effects of pramipexole and increases pramipexole concentration in blood plasma.

    Science.gov (United States)

    McCormick, P N; Fletcher, P J; Wilson, V S; Remington, G J

    2016-04-15

    Pramipexole is a dopaminergic agonist used in Parkinson's disease treatment. It is thought to exert its therapeutic and side effects through actions on dopamine D3 receptors. In a recent study, we found that at doses occupying D3 but not D2 receptors pramipexole reduced locomotion and operant responding for primary and conditioned reinforcement. These effects, however, were not blocked by a D3 receptor antagonist and were present in D3 knockout mice, suggesting non-D3 receptor mechanisms. Among the next highest affinity binding sites of pramipexole are adrenergic α2 receptors. Here we explored α2 receptor involvement in the behavioural effects of pramipexole. We found that the α2 antagonist atipamezole, which was itself behaviourally silent, counteracted pramipexole's reduction of locomotion, but not operant responding for water or a conditioned reinforcer. The resulting behavioural profile was similar to that of a higher dose of pramipexole, leading to the hypothesize that atipamezole mediates its behavioural effects by increasing pramipexole effective dose. In support of this hypothesis, we found that atipamezole increased pramipexole concentration in blood plasma. This is not likely due to an effect on drug metabolism since pramipexole is not known to undergo metabolic transformation. Future work should examine two alternative hypotheses; that pramipexole plasma concentration is elevated as the result of 1) competition with atipamezole for renal excretion, or 2) atipamezole blockade of peripheral α2 binding sites, thereby preventing pramipexole distribution to α2-rich tissues. The suggestion of adrenergic effects of pramipexole is important in light of recent interest in adrenergic pathophysiology in Parkinson's disease. PMID:26976325

  2. Effects of excitatory amino acid antagonists on evoked and spontaneous excitatory potentials in guinea-pig hippocampus.

    Science.gov (United States)

    Cotman, C W; Flatman, J A; Ganong, A H; Perkins, M N

    1986-09-01

    Evoked and spontaneous excitatory post-synaptic potentials (e.p.s.p.s) at the mossy fibre input to CA3 pyramidal neurones were recorded intracellularly in slices from the guinea-pig hippocampus. The effects of several amino acid antagonists on these responses were examined. L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP), kynurenate, and N-(p-bromobenzoyl)piperazine-2,3-dicarboxylate (pBB-PzDA) reduced the amplitude of evoked mossy fibre e.p.s.p.s without affecting membrane potential or input resistance. Antagonism of mossy fibre spontaneous miniature e.p.s.p.s (m.e.p.s.p.s) by these compounds fell into two groups. L-AP4 and L-SOP applied at concentrations that blocked evoked e.p.s.p.s did not affect amplitude distributions of spontaneous m.e.p.s.p.s. Kynurenate and pBB-PzDA significantly affected the amplitude distributions and reduced the mean amplitude of spontaneous m.e.p.s.p.s. These results are consistent with a presynaptic site of action for L-AP4 and L-SOP and a post-synaptic site of action for kynurenate and pBB-PzDA as antagonists of e.p.s.p.s at the guinea-pig mossy fibre-CA3 pyramidal neurone synapse.

  3. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  4. Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.

    Science.gov (United States)

    Yang, Zijian; Huang, Ping; Liu, Xiaohong; Huang, Shouyue; Deng, Lianfu; Jin, Zhe; Xu, Shuo; Shen, Xi; Luo, Xunda; Zhong, Yisheng

    2015-01-01

    Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection. PMID:26063641

  5. Homer regulates calcium signalling in growth cone turning

    Directory of Open Access Journals (Sweden)

    Thompson Michael JW

    2009-08-01

    Full Text Available Abstract Background Homer proteins are post-synaptic density proteins with known functions in receptor trafficking and calcium homeostasis. While they are key mediators of synaptic plasticity, they are also known to function in axon guidance, albeit by mechanisms that are yet to be elucidated. Homer proteins couple extracellular receptors – such as metabotropic glutamate receptors and the transient receptor potential canonical family of cation channels – to intracellular receptors such as inositol triphosphate and ryanodine receptors on intracellular calcium stores and, therefore, are well placed to regulate calcium dynamics within the neural growth cone. Here we used growth cones from dorsal root ganglia, a well established model in the field of axon guidance, and a growth cone turning assay to examine Homer1 function in axon guidance. Results Homer1 knockdown reversed growth cone turning from attraction to repulsion in response to the calcium-dependent guidance cues brain derived neurotrophic factor and netrin-1. Conversely, Homer1 knockdown had no effect on repulsion to the calcium-independent guidance cue Semaphorin-3A. This reversal of attractive turning suggested a requirement for Homer1 in a molecular switch. Pharmacological experiments confirmed that the operational state of a calcium-calmodulin dependent protein kinase II/calcineurin phosphatase molecular switch was dependent on Homer1 expression. Calcium imaging of motile growth cones revealed that Homer1 is required for guidance-cue-induced rise of cytosolic calcium and the attenuation of spontaneous cytosolic calcium transients. Homer1 knockdown-induced calcium transients and turning were inhibited by antagonists of store-operated channels. In addition, immunocytochemistry revealed the close association of Homer1 with the store-operated proteins TRPC1 and STIM1 within dorsal root ganglia growth cones. Conclusion These experiments provide evidence that Homer1 is an essential

  6. [In vitro effect of Hordeum vulgare on the crystallization of calcium oxalate monohydrate (whewellite)].

    Science.gov (United States)

    Djaroud, Samira; Harrache, Djamila; Amar, Amina

    2012-01-01

    The recommended conservative treatment of hyperoxaluria is mainly based on hyperhydration and ingestion of inhibitors of crystallization. In accordance with this context, the aim of this study was to determine the in vitro effect of Hordeum vulgare on calcium oxalate crystallization oxalo-dependent. The crystallization of calcium oxalate monohydrate in supersaturated aqueous solution at 37 °C, was followed in a model turbidimetric continuous in a closed system. The proposed model is very good reproducibility (CV < 10%), crystallization was monitored continuously in the presence of Hordeum vulgare at different concentrations (0.0625 to 1 g/L). The comparison of turbidimetric parameters, that characterize the growth stage of monohydrated oxalate calcium crystals and observation of the crystals obtained at the end of crystallization into scanning electron microscopy, have been able to demonstrate the inducing effect of Hordeum vulgare to 0.0625 g/L and a slight inhibitory effect at the others concentrations. PMID:23207820

  7. Effect of the presence of HCl on cyclic CO2 capture of calcium-based sorbent in calcium looping process

    International Nuclear Information System (INIS)

    Highlights: • HCl improves CO2 capture capacity of limestone in the previous a dozen cycles. • HCl sharply decreases limestone reactivity after a dozen cycles. • HCl intensifies effects of carbonation and calcination temperature on CO2 capture. • HCl enlarges effects of particle size on CO2 capture. • HCl severely aggravates the sintering of limestone after a dozen cycles. - Abstract: The effect of the presence of HCl on cyclic CO2 capture behavior of calcium-based sorbent in the calcium looping process was investigated. When HCl was present in the carbonation atmosphere, the effects of carbonation temperature, calcination temperature, HCl concentration and particle size on CO2 capture of the limestone in the multiple calcination/carbonation cycles were studied in a dual fixed-bed reactor. The presence of HCl in the carbonation atmosphere improves CO2 capture capacity of the limestone in the previous a dozen cycles, but sharply decreases its reactivity with further increasing the cycle number above a dozen. The presence of HCl intensifies the effects of carbonation temperature and calcination temperature on CO2 capture capacity of the limestone. The optimum carbonation temperature and the feasible calcination temperature for cyclic CO2 capture of the limestone in the presence of HCl should be 700 °C and below 900 °C, respectively. The cyclic CO2 capture capacity of the limestone in the previous a dozen cycles achieves the maximum in the presence of 300 ppm HCl with increasing the HCl concentration from 100 to 1000 ppm. The higher CO2 capture capacity of the limestone is achieved with smaller particle size in the presence of HCl. The presence of HCl may destroy the compact CaCO3 product layer and it is beneficial to CO2 diffusion through the layer in the initial cycles. The chlorination conversion and the molten CaCl2–CaCO3 product layer thickness of the limestone in the presence of HCl increase with the number of calcination/carbonation cycles. It

  8. [The effect of dietotherapy and supplementary calcium intake on phosphorus-calcium homeostasis in hypertensive patients].

    Science.gov (United States)

    Gladkevich, A V; Samsonov, M A; Spirichev, V B

    1990-01-01

    A total of 25 patients with essential hypertension received a hyponatrium, hypocaloric antisclerotic diet providing 800 mg Ca and 1100 mg P/day, during 18-20 days. As a result of the dietotherapy, Ca concentration in the patients' blood serum rose from 9.9 +/- 0.2 to 10.4 +/- 0.1 mg/100 ml (p = 0.02), total cholesterol level was lowered from 6.58 +/- 0.43 to 5.42 +/- 0.3 mmol/l (p less than 0.05), Na+ and K+ distribution between the blood plasma and red blood cells was improved, and the arterial blood pressure was normalized in all the patients investigated. It dropped from 162 +/- 3.8/102 +/- 1.8 mm Hg before the treatment to 129 +/- 2.1/83.4 +/- 2.2 mm Hg after the treatment. Additional intake of 850 mg Ca/day, as CaCO3, decreased parathormone level in the blood serum from 0.40 +/- 0.03 to 0.23 ng/ml (p less than 0.01), intensified the hypolipidemic effect of the ration, and did not influence the degree of arterial blood pressure reduction under the action of this ration. Optimization of Ca consumption plays an important role in the combined dietotherapy of essential hypertension. PMID:2378097

  9. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    Science.gov (United States)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  10. Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze.

    Science.gov (United States)

    Dunn, R W; Corbett, R; Fielding, S

    1989-10-01

    The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.

  11. Effects of adrenalectomy on the alpha-adrenergic regulation of cytosolic free calcium in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Freudenrich, C.C.; Borle, A.B.

    1988-06-25

    We have previously published that bilateral adrenalectomy in the rat reduces the Ca2+-mediated alpha-adrenergic activation of hepatic glycogenolysis, while it increases the cellular calcium content of hepatocytes. In the experiments presented here, the concentration of cytosolic free calcium (Ca2+i) at rest and in response to epinephrine was measured in aequorin-loaded hepatocytes isolated from sham and adrenalectomized male rats. We found that in adrenalectomized rats the resting Ca2+i was elevated, the rise in Ca2+i evoked by epinephrine was reduced, and the rise in /sup 45/Ca efflux that follows such stimulation was depressed. Furthermore, the slope of the relationship between Ca2+i and calcium efflux was decreased 60% in adrenalectomized. Adrenalectomy did not change Ca2+ release from intracellular calcium pools in response to IP3 in saponin-permeabilized hepatocytes. The EC50 for inositol 1,4,5-triphosphate and the maximal Ca2+ released were similar in both sham and adrenalectomized animals. Finally, the liver calmodulin content determined by radioimmunoassay was not significantly different between sham and adrenalectomized rats. These results suggest that 1) adrenalectomy reduces calcium efflux from the hepatocyte, probably by an effect on the plasma membrane (Ca2+-Mg2+)-ATPase-dependent Ca2+ pump and thus alters cellular calcium homeostasis; 2) adrenalectomy decreases the rise in Ca2+i in response to epinephrine; 3) this decreased rise in Ca2+i is not due to defects in the intracellular Ca2+ storage and mobilization processes; and 4) the effects of adrenalectomy on cellular calcium metabolism and on alpha-adrenergic activation of glycogenolysis are not caused by a reduction in soluble calmodulin.

  12. Effect of dendroaspis natriuretic peptide (DNP) on L-type calcium channel current and its pathway.

    Science.gov (United States)

    Zhang, Shu-Ying; Cai, Zheng-Xu; Li, Ping; Cai, Chun-Yu; Qu, Cheng-Long; Guo, Hui-Shu

    2010-09-24

    Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, relaxes gastrointestinal smooth muscle. L-type calcium channel currents play an important role in regulating smooth muscle contraction. The effect of DNP on L-type calcium channel currents in gastrointestinal tract is still unclear. This study was designed to investigate the effect of DNP on barium current (I(Ba)) through the L-type calcium channel in gastric antral myocytes of guinea pigs and cGMP-pathway mechanism. The whole-cell patch-clamp technique was used to record L-type calcium channel currents. The content of cGMP in guinea pig gastric antral smooth muscle and perfusion solution was measured using radioimmunoassay. DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in perfusion medium. DNP concentration-dependently inhibited I(Ba) in freshly isolated guinea pig gastric antral circular smooth muscle cells (SMCs) of guinea pigs. DNP-induced inhibition of I(Ba) was partially blocked by LY83583, an inhibitor of guanylate cyclase. KT5823, a cGMP-dependent protein kinase (PKG) inhibitor, almost completely blocked DNP-induced inhibition of I(Ba). However, DNP-induced inhibition of I(Ba) was potentiated by zaprinast, an inhibitor of cGMP-sensitive phosphodiesterase. Taken together, DNP inhibits L-type calcium channel currents via pGC-cGMP-PKG-dependent signal pathway in gastric antral myocytes of guinea pigs. PMID:20594955

  13. Antilithic effects of extracts from Urtica dentata hand on calcium oxalate urinary stones in rats.

    Science.gov (United States)

    Xiang, Ming; Zhang, Shasha; Lu, Jingli; Li, Lulu; Hou, Wenrui; Xie, Mingxing; Zeng, Ying

    2011-10-01

    This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones. The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25% ethylene glycol (EG) and 1% ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging. The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE), N-butanol extract (NBE), aqueous extract (AqE) of UDH, Jieshitong (positive control drug), and saline, respectively. Treatment with NBE significantly reduced the elevated levels of urinary calcium, uric acid, phosphate, as well as increased urinary output. Accordingly, the increased calcium, oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats. In addition, NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine. Taken together, these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function. PMID:22038359

  14. Effect of calcium triphosphate cement on proximal humeral fracture osteosynthesis: a finite element analysis.

    Science.gov (United States)

    Kennedy, Jim; Feerick, Emer; McGarry, Patrick; FitzPatrick, David; Mullett, Hannan

    2013-08-01

    PURPOSE. To measure the effect of void-filling calcium triphosphate cement on the loads at the implant-bone interface of a proximal humeral fracture osteosynthesis using a finite element analysis. METHODS. Finite element models of a 3-part proximal humeral fracture fixed with a plate with and without calcium triphosphate cement augmentation were generated from a quantitative computed tomography dataset of an intact proximal humerus. Material properties were assigned to bone fragments using published expressions relating Young's modulus to local Hounsfield number. Boundary conditions were then applied to the model to replicate the physiological loads. The effect of void-filling calcium triphosphate cement was analysed. RESULTS. When the void was filled with calcium triphosphate cement, the pressure gradient of the bone surrounding the screws in the medial fracture fragment decreased 97% from up to 21.41 to 0.66 MPa. Peak pressure of the fracture planes decreased 95% from 6.10 to 0.30 MPa and occurred along the medial aspect. The mean stress in the screw locking mechanisms decreased 78% from 71.23 to 15.92 MPa. The angled proximal metaphyseal screw had the highest stress. CONCLUSION. Augmentation with calcium triphosphate cement improves initial stability and reduces stress on the implant-bone interface. PMID:24014777

  15. The effects of apple pomace, bentonite and calcium superphosphate on swine manure aerobic composting.

    Science.gov (United States)

    Jiang, Jishao; Huang, Yimei; Liu, Xueling; Huang, Hua

    2014-09-01

    The effects of additives such as apple pomace, bentonite and calcium superphosphate on swine manure composting were investigated in a self-built aerated static box (90 L) by assessing their influences on the transformation of nitrogen, carbon, phosphorous and compost maturity. The results showed that additives all prolonged the thermophilic stage in composting compared to control. Nitrogen losses amounted to 34-58% of the initial nitrogen, in which ammonia volatilization accounted for 0.3-4.6%. Calcium superphosphate was helpful in facilitating composting process as it significantly reduced the ammonia volatilization during thermophilic stage and increased the contents of total nitrogen and phosphorous in compost, but bentonite increased the ammonia volatilization and reduced the total nitrogen concentration. It suggested that calcium superphosphate is an effective additive for keeping nitrogen during swine manure composting. PMID:24928053

  16. Effect of galactooligosaccharides on calcium absorption and preventing bone loss in ovariectomized rats.

    Science.gov (United States)

    Chonan, O; Matsumoto, K; Watanuki, M

    1995-02-01

    The effects of galactooligosaccharides (GOS), a mixture of galactosyl oligosaccharides formed from lactose by the transgalactosyl reaction of beta-D-galactosidase derived from Bacillus circulans, on calcium absorption and prevention of bone loss were examined in ovariectomized (OVX) Wistar rats. Rats fed on a diet containing GOS absorbed calcium more efficiently than those on the control diet after 8-10 days and 18-20 days, and the bone (femur and tibia) ash weight and tibia calcium content of OVX rats fed on the GOS diet were significantly higher than those of the control animals. Although the serum total cholesterol of the ovariectomized rats was significantly elevated, GOS produced a significant hypocholesterolemic effect in the OVX rats. GOS, which is fermented by bacteria in the lower part of the intestine, enhanced volatile fatty acid production, and thus prevented bone loss and lower serum total cholesterol concentration in the ovariectomized rats.

  17. Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells.

    Science.gov (United States)

    Peetsch, Alexander; Greulich, Christina; Braun, Dieter; Stroetges, Christian; Rehage, Heinz; Siebers, Bettina; Köller, Manfred; Epple, Matthias

    2013-02-01

    Spherical silver-doped calcium phosphate nanoparticles were synthesized in a co-precipitation route from calcium nitrate/silver nitrate and ammonium phosphate in a continuous process and colloidally stabilized by carboxymethyl cellulose. Nanoparticles with 0.39 wt% silver content and a diameter of about 50-60 nm were obtained. The toxic effects toward mammalian and prokaryotic cells were determined by viability tests and determination of the minimal inhibitory and minimal bactericidal concentrations (MIC and MBC). Three mammalian cells lines, i.e. human mesenchymal stem cells (hMSC) and blood peripheral mononuclear cells (PBMC, monocytes and T-lymphocytes), and two prokaryotic strains, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used. Silver-doped calcium phosphate nanoparticles and silver acetate showed similar effect toward mammalian and prokaryotic cells with toxic silver concentrations in the range of 1-3 μg mL(-1).

  18. Effect of Calcium Leaching on the Properties of Cement-based Composites

    Institute of Scientific and Technical Information of China (English)

    LLIN Weiting; CHENG An; HUANG Ran; CHEN Chuntao; ZHOU Xingang

    2011-01-01

    Leaching is one of the major factors that alter the mechanical properties of cementbased composites.This study is aimed to investigate the effect of leaching on the properties of cementbased composites.Specimens with two water/cementitious ratios and two mineral admixtures were tested.An electrical potential was applied to accelerate the leaching process.Compressive strength test,scanning electronic microscopy,thermogravimetric analysis and X-ray diffraction analysis were conducted.Test results demonstrated that the calcium leaching reduced compressive strengths of concrete specimens,and such effect was prominent on the specimens without mineral admixtures.The leaching resistance increased with a decrease in water/cementitious ratio and an increase in amount of mineral admixtures.The mineral admixtures would reduce the amount of calcium hydroxide and refine the pore structure through pozzolanic reactions.A fair relationship was found between the calcium leaching and the compressive strength.

  19. Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer

    OpenAIRE

    KUGA, Milton Carlos; DUARTE Marco Antonio Hungaro; SANT'ANNA-JÚNIOR, Arnaldo; KEINE, Kátia Cristina; FARIA, Gisele; Andrea Abi Rached DANTAS; GUIOTTI, Flávia Angélica

    2014-01-01

    Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. Objective: The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF) or containing 5% (MTAF5) or 10% (MTAF10) calcium hydroxide (CH), in weight, in comparison with AH Plus sealer. Material and Methods: The...

  20. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats.

    Science.gov (United States)

    Guo, Lili; Shi, Mingyi; Zhang, Ling; Li, Guangzhi; Zhang, Lingxiang; Shao, Hu; Fang, Penghua; Ma, Yingping; Li, Jian; Shi, Qiaojia; Sui, Yumei

    2011-08-01

    Seeing that galanin increases animal body weight on the conditions of inhibiting insulin secretion and animals with metabolic disorder of galanin easily suffer from diabetes, we postulate that endogenous galanin is necessary to reduce insulin resistance in adipocytes. To test this hypothesis, we compared four groups of rats to examine whether an increase in galanin secretion stimulated by swimming may reduce insulin resistance. The rats from sedentary and trained drug groups were injected by M35, a galanin antagonist. The rats from trained control and trained drug groups swam after each injection for four weeks. We found that exercise significantly elevated plasma galanin contents and glucose transporter 4 (GLUT4) mRNA levels in adipocytes. Meanwhile, M35 treatment reduced GLUT4 and GLUT4 mRNA levels, and glucose infusing rates in euglycemic-hyperinsulinemic clamp tests. The ratios of GLUT4 concentrations at plasma membranes to total cell membranes in both drug groups were lower compared with each control group, respectively. These observations suggest that endogenous galanin reduces insulin resistance by increasing GLUT4 contents and promoting GLUT4 transportation from intracellular membranes to plasma membranes in adipocytes. Galanin is an important hormone to reduce insulin resistance in rats. PMID:21664358

  1. Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Shui-xian SHEN; Li-hua ZHU; En-bi WANG; Zeng-can YE; Jun LIN; Li-he GUO; Fei-hong LUO; Xi-hong LIU; Xin FANG

    2004-01-01

    AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A,C182S, de1186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean±SD)values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65±10) ng for hGHA1, (27±5.6) ng for hGHA2, and (10±0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.

  2. Antagonistic effects between magnetite nanoparticles and a hydrophobic surfactant in highly concentrated Pickering emulsions.

    Science.gov (United States)

    Vílchez, Alejandro; Rodríguez-Abreu, Carlos; Menner, Angelika; Bismarck, Alexander; Esquena, Jordi

    2014-05-13

    Herein we present a systematic study of the antagonistic interaction between magnetite nanoparticles (Fe3O4) and nonionic hydrophobic surfactant in Pickering highly concentrated emulsions. Interfacial tension measurements, phase behavior, and emulsion stability studies, combined with electron microscopy observations in polymerized systems and magnetometry, are used to support the discussion. First, stable W/O highly concentrated emulsions were obtained using partially hydrophobized magnetite nanoparticles. These emulsions experienced phase separation when surfactant is added at concentrations as low as 0.05 wt %. Such phase separation arises from the preferential affinity of the surfactant for the nanoparticle surfaces, which remarkably enhances their hydrophobicity, leading to a gradual desorption of nanoparticles from the interface. W/O emulsions were obtained at higher surfactant concentrations, but in this case, these emulsions were mainly stabilized by surfactant molecules. Therefore, stable emulsions could be prepared in two separate ranges of surfactant concentrations. After polymerization, low-density macroporous polymers were obtained, and the adsorption and aggregation of nanoparticles was analyzed by transmission electron microscopy. The progressive displacement of the nanoparticles was revealed: from the oil-water interface, in which aggregated nanoparticles were adsorbed, forming dense layers, to the continuous phase of the emulsions, where small nanoparticle aggregates were randomly dispersed. Interestingly, the results also show that the blocking temperature of the iron oxide superparamagnetic nanoparticles embedded in the macroporous polymers could be modulated by appropriate control of the concentrations of both surfactant and nanoparticles. PMID:24738961

  3. Effect of casein phosphopeptide - amorphous calcium phosphate containing chewing gum on salivary concentration of calcium and phosphorus: An in-vivo study

    Directory of Open Access Journals (Sweden)

    B P Santhosh

    2012-01-01

    Full Text Available Aim: Caries clinical trials of sugar-free chewing gum have shown that the gum is noncariogenic and in fact has anticariogenic effect through the stimulation of saliva. Sugar-free gums, therefore, may be an excellent delivery vehicle for safe and effective additive, capable of promoting enamel remineralization. Casein phosphopeptide - amorphous calcium phosphate (CPP-ACP nanocomplexes incorporated into sugar-free chewing gum have shown to remineralize enamel subsurface lesions in situ. So this study was conducted to evaluate the effect of CPP-ACP containing sugar-free chewing gum on salivary concentration of calcium and phosphorous. Materials and Methods : Unstimulated saliva from each 24 selected subjects was collected. Then each subject was given two pellets of chewing gum containing CPP-ACP and asked to chew for a period of 20 min, after which saliva samples were collected from each individual. Once all the samples were collected they were assessed for calcium and phosphorous concentration using affiliated reagent kits and photometer. Statistical Analysis Used: Data obtained were analyzed using student′s paired t test. Results: Significant difference was found in the calcium and phosphorus concentration of saliva before and after chewing CPP-ACP containing chewing gum. Conclusions: Chewing of CPP-ACP containing chewing gum showed a significant increase in the salivary concentration of calcium for a prolonged period of time hence it may help in the remineralization of tooth surfaces.

  4. Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth 1 2 3 4

    OpenAIRE

    Goldberg, Gail R.; Jarjou, Landing MA; Tim J Cole; Prentice, Ann

    2013-01-01

    Background: Dietary calcium intake in rural Gambian women is very low (∼350 mg/d) compared with international recommendations. Studies have suggested that calcium supplementation of women receiving low-calcium diets significantly reduces risk of pregnancy hypertension. Objective: We tested the effects on blood pressure (BP) of calcium carbonate supplementation (1500 mg Ca/d) in pregnant, rural Gambian women. Design: The study was a randomized, double-blind, parallel, placebo-controlled supple...

  5. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    International Nuclear Information System (INIS)

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [3H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca2+-containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca2+ to the medium. This result was consistent with a competition between Ca2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca2+

  6. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha;

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  7. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

  8. Serum calcium response following oral zinc oxide administrations in dairy cows

    DEFF Research Database (Denmark)

    Thilsing-Hansen, T; Jørgensen, R J; Thilsing, Trine

    2001-01-01

    of the lactating cows dropped dramatically indicating the existence of an antagonistic effect between Zn and Ca. The first Zn induced hypocalcaemic episode in the lactating cows was followed by a rise in serum calcium to a level above the pre-dosing level and above the mean value of the control group. The depth...

  9. Differential effects of three 5-HT receptor antagonists on the performance of rats in attentional and working memory tasks.

    Science.gov (United States)

    Ruotsalainen, S; Sirviö, J; Jäkälä, P; Puumala, T; MacDonald, E; Riekkinen, P

    1997-05-01

    The effects of three different serotonin (5-HT) receptor antagonists (ketanserin, methysegide, methiothepin) in the modulation of attention, working memory and behavioural activity were investigated in this study by assessing the performance of rats in two separate cognitive models; the 5-choice serial reaction time (5-CSRT) task, which measures attention, and the delayed non-matching to position (DNMTP) task, which measures working memory. Methysergide and methiothepin bind at the 5-HT1 and 5-HT2 as well as the 5-HT5-7 receptors, with varying degrees of selectivity, and ketanserin binds at the 5-HT2A receptors rather selectively. None of these agents bind to any significant extent to 5-HT3 or 5-HT4 receptors. In the 5-CSRT task, neither methiothepin (0.15 mg/kg) nor ketanserin (1.0 and 3.0 mg/kg) impaired the choice accuracy of rats, although they induced sedation. The low doses of methysergide (1.5 and 3.0 mg/kg) slightly increased the behavioural activity of rats, whereas the high dose of methysergide (15.0 mg/kg) reduced behavioural activity and slightly reduced choice accuracy of the rats in the attentional task (monitoring of visual stimuli) under the baseline conditions or curtailed stimulus duration. This effect was not augmented at the reduced stimulus intensity. These findings suggest that the high dose of methysergide did not interfere with the visual discrimination of rats. Furthermore, methysergide did not reduce motivation for this task, since it did not increase food collection latencies. In the DNMTP task, methiothepin (0.15 mg/kg) induced a delay non-dependent deficit in choice accuracy. This could be due to an impaired alternation ability or akinesia, which increases an actual delay between sample and choice. Methiothepin (0.15 mg/kg) also interfered with behavioural activity of rats. Interestingly, ketanserin (1.0 mg/kg and 3.0 mg/kg) and methysergide (3.0-15.0 mg/kg) neither impaired the choice accuracy nor reduced the behavioural activity of

  10. Effect of Calcium Oxide Microstructure on the Diffusion of Isotopes

    CERN Document Server

    Fernandes Ramos, João Pedro; Stora, T

    2012-01-01

    Calcium oxide (CaO) powder targets have been successfully used at CERN-ISOLDE to produce neutron deficient exotic argon and carbon isotopes under proton irradiation at high temperatures (>1000°C). These targets outperform the other related targets for the production of the same beams. However, they presented either slow release rates (yields) from the beginning or a rapid decrease over time. This problem was believed to come from the target microstructure degradation, justifying the material investigation. In order to do so, the synthesis, reactivity in ambient air and sintering kinetics of CaO were studied, through surface area determination by N2 adsorption, X-ray diffraction for crystalline phase identification and crystallite size determination, and scanning and transmission electron microscopy to investigate the microstructure. The synthesis studies revealed that a nanometric material is obtained from the decarbonation of CaCO3 in vacuum at temperatures higher than 550°C, which is very reactive in air....

  11. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials

    DEFF Research Database (Denmark)

    Christensen, R.; Lorenzen, Janne Kunchel; Svith, Carina Roholm;

    2009-01-01

    Observational studies have found that dietary calcium intake is inversely related to body weight and body fat mass. One explanatory mechanism is that dietary calcium increases faecal fat excretion. To examine the effect of calcium from dietary supplements or dairy products on quantitative faecal...... fat excretion, we performed a systematic review with meta-analysis. We included randomized, controlled trials of calcium (supplements or dairy) in healthy subjects, where faecal fat excretion was measured. Meta-analyses used random-effects models with changes in faecal fat excreted expressed...

  12. Neuroprotective effects of the AMPA antagonist PNQX in oxygen-glucose deprivation in mouse hippocampal slice cultures and global cerebral ischemia in gerbils

    DEFF Research Database (Denmark)

    Montero, Maria; Nielsen, Marianne; Rønn, Lars Christian B;

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in tr...

  13. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Olsen, G M; Wiborg, O;

    2009-01-01

    AChR subtype/s involved remains unknown. In this study, we systematically compared the effects of non-selective and selective nicotinic agonists and antagonists in two different tests for antidepressant effects in mice: the tail suspension test and the forced swim test. Compounds: nicotine, RJR-2403 (alpha4...

  14. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    . Accordingly, the fraction of apoptotic/dead cells significantly increased following addition of plerixafor to rituximab treatment. Furthermore, exposure of DLBCL cells to plerixafor resulted in a significant decrease in CXCR4 fluorescence intensity. CONCLUSIONS: Based on our results, implying that the anti......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment......-proliferative/pro-apoptotic effect of rituximab on DLBCL cells can be synergistically enhanced by the CXCR4 antagonist plerixafor, addition of plerixafor to the R-CHOP regimen can be suggested to improve treatment outcome for DLBCL patients....

  15. Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure

    DEFF Research Database (Denmark)

    Olsen, Inge C; Kjekshus, John K; Torp-Pedersen, Christian;

    2009-01-01

    AIMS: Myocardial 5-HT(4) serotonin (5-HT) receptors are increased and activated in heart failure (HF). Blockade of 5-HT(4) receptors reduced left ventricular (LV) remodelling in HF rats. We evaluated the effect of piboserod, a potent, selective, 5-HT(4) serotonin receptor antagonist, on LV function...... weeks up titration. The primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI). Secondary endpoints were LV volumes, N-terminal pro-brain natriuretic peptide, norepinephrine, quality of life, and 6 min walk test. Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0...... of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues. CONCLUSION: Although patients with chronic HF had a small but significant improvement in LVEF when treated with piboserod for 24 weeks, the result...

  16. The Effect of Calcium Hydroxide As an Intracanal Medication of The Apical Microleakage

    Directory of Open Access Journals (Sweden)

    Heshmat Mohajer AR

    2011-12-01

    Full Text Available Background and Aims: Nowadays, calcium hydroxide is used as a dressing for canal sterilization and repair progression of apical lesions. The aim of this study was to investigate the effect of calcium hydroxide as an intracanal medicament on the apical microleakage of root filling.Materials and Methods: In this experimental study, 46 extracted single-rooted human teeth were instrumented with step-back technique to master apical file (MAF size 35. Specimens were randomly divided into 2 groups (n = 20. In group 1, the specimens were treated with calcium hydroxide intracanal medication; and in group 2, the samples did not receive any medication. The teeth were incubated in 100% humidity at 37°C for one week. After that, calcium hydroxide was removed using irrigation with normal saline and reaming with MAF. The root canals were obturated with gutta- percha and AH26 sealer using lateral compaction technique. Specimens were incubated in 100% humility at 37°C for 72 hours and then immersed in India ink for 1 week. Finally, the teeth were cleared and the maximum linear dye penetration was measured under a stereomicroscope at 4X magnification. The data were analyzed by T-test and Chi-square.Results: There was no significant difference between the two experimental groups (P=0.068. Conclusion: The findings of this study indicated that using calcium hydroxide as an intracanal medicament did not influence the apical microleakage after final obturation of the root canal system.

  17. Effects of Sevelamer Hydrochloride and Calcium Carbonate on Renal Osteodystrophy in Hemodialysis Patients

    Science.gov (United States)

    Ferreira, Aníbal; Frazão, João Miguel; Monier-Faugere, Marie-Claude; Gil, Célia; Galvao, José; Oliveira, Carlos; Baldaia, Jorge; Rodrigues, Ilidio; Santos, Carla; Ribeiro, Silvia; Hoenger, Regula Mueller; Duggal, Ajay; Malluche, Hartmut H.

    2008-01-01

    Disturbances in mineral metabolism play a central role in the development of renal bone disease. In a 54-wk, randomized, open-label study, 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone. Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline (59%). Serum phosphorus, calcium, and intact parathyroid hormone were well controlled in both groups, although calcium was consistently lower and intact parathyroid hormone higher among patients who were randomly assigned to sevelamer. Compared with baseline values, there were no changes in mineralization lag time or measures of bone turnover (e.g., activation frequency) after 1 yr in either group. Osteoid thickness significantly increased in both groups, but there was no significant difference between them. Bone formation rate per bone surface, however, significantly increased from baseline only in the sevelamer group (P = 0.019). In addition, of those with abnormal microarchitecture at baseline (i.e., trabecular separation), seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group. In summary, sevelamer resulted in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate, but bone formation increased and trabecular architecture improved with sevelamer. Further studies are required to assess whether these changes affect clinical outcomes, such as rates of fracture. PMID:18199805

  18. Effect of calcium/sodium ion exchange on the osmotic properties and structure of polyelectrolyte gels.

    Science.gov (United States)

    Horkay, Ferenc; Basser, Peter J; Hecht, Anne-Marie; Geissler, Erik

    2015-12-01

    We discuss the main findings of a long-term research program exploring the consequences of sodium/calcium ion exchange on the macroscopic osmotic and elastic properties, and the microscopic structure of representative synthetic polyelectrolyte (sodium polyacrylate, (polyacrylic acid)) and biopolymer gels (DNA). A common feature of these gels is that above a threshold calcium ion concentration, they exhibit a reversible volume phase transition. At the macroscopic level, the concentration dependence of the osmotic pressure shows that calcium ions influence primarily the third-order interaction term in the Flory-Huggins model of polymer solutions. Mechanical tests reveal that the elastic modulus is practically unaffected by the presence of calcium ions, indicating that ion bridging does not create permanent cross-links. At the microscopic level, small-angle neutron scattering shows that polyacrylic acid and DNA gels exhibit qualitatively similar structural features in spite of important differences (e.g. chain flexibility and chemical composition) between the two polymers. The main effect of calcium ions is that the neutron scattering intensity increases due to the decrease in the osmotic modulus. At the level of the counterion cloud around dissolved macroions, anomalous small-angle X-ray scattering measurements made on DNA indicate that divalent ions form a cylindrical sheath enveloping the chain, but they are not localized. Small-angle neutron scattering and small-angle X-ray scattering provide complementary information on the structure and interactions in polymer solutions and gels. PMID:26614803

  19. Effects of Different Calcium Carbide Doses on Some Quality Criteria of Kiwifruit (Actinidia deliciosa

    Directory of Open Access Journals (Sweden)

    E. Bal

    2006-05-01

    Full Text Available This research was performed to determine effects of calcium carbide treatments at different doses onripening physiology of cv. Hayward. For this aim, calcium carbide doses of 0, 0.3, 0.5 and 0.7 g were usedand characteristics such as fruit firmness, soluble solids content, titratable acidity, pH of fruit juice, vitamin Ccontent and sensory evaluation, comprising fruit quality were examined with daily during 7 days at roomtemperature (22±0.50C conditions. At the end of the study, increase in softening and sensory evaluationvalues was detected based on the calcium carbide dose and ripening time. During the ripening of kiwifruits, itwas observed that titratable acidity and vitamin C content reduced and pH of fruit juice and soluble solids inwater increased, generally. At the end of 7th day, higher edible fruit quality was determined in fruits treatedwith 0.7 g. calcium carbide and 0.5g and 0.3 g calcium carbide treatments followed it. At the end of theperiod, there was no evidence about edible quality of control fruits.

  20. Effect of exhausting exercise and calcium supplementation on potassium, magnesium, copper, zinc and calcium levels in athletes

    International Nuclear Information System (INIS)

    Present study was performed to determine four week calcium supplementation and athleticism exercise on plasma potassium, calcium, magnesium, cupper and zinc levels in resting and exhaustion. Research was carried out on 30 healthy male people. Group 1; Exercise, Group 2; Exercise + Calcium supplementation, Group 3; Sedentary + Calcium supplemented. All elements levels increased by exhausting exercise (P<0.05). Plasma K and Ca levels increased in exercise group after supplementation (P<0.05). Ca levels increased in exercise + supplemented group (P<0.05). This increase was much more in group three (P<0.05). Plasma Cu levels increased by Ca supplementation in sedentary (P<0.05). Exhausting exercise increased Zn levels in sedentary after supplementation (P<0.05). The results of present study show that calcium supplementation for 4 week does not have clear affect on potassium and Mg. However, calcium levels were increased by supplementation and Cu after the supplementation. It was also exhausting exercise that caused increase in all parameters. (author)

  1. [Clinical efficacy of calcium channel blockers slow the third generation of lercanidipine in the treatment of patients with arterial hypertension and metabolic disorders (review)].

    Science.gov (United States)

    Tabidze, G A; Gezeli, T D; Tsibadze, T A; Dolidze, N M

    2015-02-01

    Arterial hypertension is the most common risk factor in patients with metabolic disorders. In the selection of antihypertensive therapy it is necessary to consider not only the anti-hypertensive and organoprotective effects of drugs and their metabolic effects, which has prognostic value. Calcium antaginists, along. Lercanidipine related to the third generation dihydripyridine calcium antagonist, has been much more selective for the so-called slow calcium channels of vascular smooth muscle cells, which is associated with a good hypertensive, organo and metabolic action. Combination therapy with an ACE inhibitor and a calcium channel blocker is also a justified tactic for the management of patients with high-risk cardiovascular and metabolic disorders. Attention is paid new fixed combinations, including angiotensin converting enzyme inhibitors and calcium antagonists.

  2. Neuroprotection Against NMDA Induced Cell Death in Rat Nucleus Basalis by Ca2+ Antagonist Nimodipine, Influence of Aging and Developmental Drug Treatment

    NARCIS (Netherlands)

    Luiten, P.G.M.; Douma, B.R.K.; Zee, E.A. van der; Nyakas, C.

    1995-01-01

    In the current study the neuroprotective effect of the L-type calcium channel antagonist nimodipine in rat brain was investigated in N-methyl-D-aspartate-induced neuronal degeneration in vivo. In the present model NMDA was unilaterally injected in the magnocellular nucleus basalis and the neurotoxic

  3. Pharmacological modulation of the short-lasting effects of antagonistic direct current-stimulation over the human motor cortex

    Directory of Open Access Journals (Sweden)

    Leila eChaieb

    2012-07-01

    Full Text Available Combined administration of transcranial direct current stimulation (tDCS with either pergolide (PGL or D-cycloserine (D-CYC can prolong the excitability-diminishing effects of cathodal, or the excitability enhancing effect of anodal stimulation for up to 24hrs poststimulation. However, it remains unclear whether the potentiation of the observed aftereffects is dominated by the polarity and duration of the stimulation, or the dual application of combined stimulation and drug administration. The present study looks at whether the aftereffects of oral administration of PGL (a D1/D2 agonist or D-CYC (a partial NMDA receptor agonist, in conjunction with the short duration antagonistic application of tDCS (either 5 min cathodal followed immediately by 5 min anodal or vice versa, that alone only induces short lasting aftereffects, can modulate cortical excitability in healthy human subjects, as revealed by a single-pulse MEP (motor-evoked-potential paradigm. Results indicate that the antagonistic application of DC currents induces short-term neuroplastic aftereffects that are dependent upon the polarity of the second application of short-duration tDCS. The application of D-cycloserine resulted in a reversal of this trend and so consequently a marked inhibition of cortical excitability with the cathodal-anodal stimulation order was observed. The administration of pergolide showed no significant aftereffects in either case. These results emphasise that the aftereffects of tDCS are dependent upon the stimulation orientation, and mirror the findings of other studies reporting the neuroplasticity inducing aftereffects of tDCS, and their prolongation when combined with the administration of CNS active drugs.

  4. The effect of the calcium source, level and the particle size on calcium retention, eggshell quality and the overall calcium requirement in laying hens

    OpenAIRE

    Lichovnikova, Martina

    2007-01-01

    Abstract Four different sources of calcium in isonitrogenous and isoenergeric diets were fed to laying hens for two-week digestion trial when they were 56 and 57 weeks old. The mineral percentages in the feed were as follows: 29% fine limestone (LF) and 71% large limestone (LG), 32% fine limestone (LF) and 68% eggshell, 32% fine limestone (LF) and 68% oyster shell, 50% fine limestone and 50% large limestone (LG). The contents of these sources of calcium in the diets were as follows...

  5. The effects of citric acid on the hydration of calcium phosphate cement

    Institute of Scientific and Technical Information of China (English)

    DAI Hong-lian; YAN Yu-hua; WANG You-fa; LI Shi-pu

    2001-01-01

    @@ INTRODUCTION Calcium phosphate cements (CPC) overcome the practical disadvantages of blocks or granulesl can be handled as a paste and sit in situ. Their structure and composition close to that of HAP make them biocompatible materials. 2 The conventional calcium phosphate cement had some problems such as long setting time (30~60 min) and low compressive strength, etc. In our system, an α-TCP/TTCP powder mixture was mixed with water containing citric acid to control the setting time and compressive strength. In this paper, the effects of various concentration citric acid solutions on the properties of the cement are reported.

  6. Effect of Pomegranate Juice on Bone Calcium Content and Body Weight of

    OpenAIRE

    Fatemeh Parvin; Malihezaman Monsefi; Tahereh Talaei-Khozani

    2014-01-01

    Background: Pomegranate juice has several antioxidant components such as flavenoids and mineral materials such as sodium and potassium. In this study the effects of pomegranate juice on bone calcium content and body weight of adult mice were survived. Materials and Methods: In this applied study two doses (3.3 and 6.6 ml/kg) of pomegranate juice (PJ) were gavaged to female mice for 30 days. Animals were weighed at days of 0, 5, 10, 15, 20, 25 and 30. Bone calcium contents were measured by ...

  7. Serum Proteins Stabilized Calcium Phosphate Nanoparticles and Its Effect on Bel-7402 Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Hydroxyapatite has a high affinity to biological macromolecules, especially to proteins. Bovine serum proteins were extracted to be used as stablizer to prepare calcium phosphate nanoparticles. 167.7 am and87.7 nm particles were respectively prepared by using bovine serum protein fractions at the concentration of 0.5mg/mL and 1.0 mg/mL. As the polysaccharide stabilized hydroxyapatite nanoparticles, the protein-stablized nanoparticles also inhibited the proliferation rate of Bel-7402 cells. It suggested that proteins could be applied to prepare calcium phosphate nanoparticles and it also has the anticancer effect.

  8. Calcium Electroporation: Evidence for Differential Effects in Normal and Malignant Cell Lines, Evaluated in a 3D Spheroid Model

    OpenAIRE

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha; Gehl, Julie; Rols, Marie-Pierre

    2015-01-01

    Background Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill efficacy–and normal cell sensitivity. Methods Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different h...

  9. Antagonistic effects of atipamezole, flumazenil and 4-aminopyridine against anaesthesia with medetomidine, midazolam and ketamine combination in cats.

    Science.gov (United States)

    Ueoka, Naotami; Hikasa, Yoshiaki

    2008-02-01

    Antagonistic effects of atipamezole (ATI), flumazenil (FLU) and 4-aminopyridine (4AP) alone and in various combinations after administration of medetomidine-midazolam-ketamine (MED-MID-KET) were evaluated in cats. Animals were anaesthetised with MED (50 microg/kg), MID (0.5 mg/kg) and KET (10 mg/kg) given intramuscularly. Twenty minutes later, physiological saline, ATI (200 microg/kg), FLU (0.1 mg/kg), 4AP (0.5 mg/kg), ATI-FLU, FLU-4AP, ATI-4AP or ATI-FLU-4AP was administered intravenously. FLU, 4AP alone, or FLU-4AP did not effectively antagonise the anaesthesia, hypothermia, bradycardia, and bradypnoea induced by MED-MID-KET. ATI alone was effective. ATI-FLU, ATI-4AP and ATI-FLU-4AP combinations produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-4AP was the most effective in antagonising the anaesthetic effects, but was associated with tachycardia, tachypnoea, excitement, and muscle tremors. Combinations with ATI are more effective for antagonising anaesthesia, but ATI-FLU-4AP is not suitable. PMID:17766159

  10. The effect of phototherapy on urinary calcium excretion in term neonates

    Directory of Open Access Journals (Sweden)

    Afshin Safaei Asl

    2016-01-01

    Full Text Available Phototherapy is the most common, most effective, and least dangerous treatment method for neonatal hyperbilirubinemia and is the treatment of the first choice for neonatal icterus. Hypocalcemia is one of the lesser-known complications of phototherapy. Some studies have shown a relationship between increased urinary calcium excretion and phototherapy-induced hypocalcemia. We aimed to assess the effect of phototherapy on urinary calcium excretion in term neonates. This before-after study was performed on 80 term neonates having hyper- bilirubinemia referred to the 17thShahrivar Hospital, Rasht, Guilan Province, Northern Iran, over a one-year period from May 2013 to May 2014. Electrocardiography was performed to measure QTc in all neonates at admission and 48 h after phototherapy. Blood and urine samples were taken from all neonates before and 48 h after phototherapy. Phototherapy was performed using four lamps with similar wavelengths from a distance of 20 cm. The serum and urinary calcium and sodium levels and urinary creatinine level before and after phototherapy were measured and compared. Data were analyzed using SPSS software, version 16. The mean age of the study subjects was 7.01 ± 4.13 days. We did not find any significant difference between urinary calcium levels (P = 0.0001, urinary creatinine levels (P = 0.954, or the calcium/creatinine ratio (P = 0.086 before and after phototherapy. The neonates′ mean ± standard deviation plasma as well as urinary sodium levels differed before and after phototherapy; the difference was not statistically significant (P = 0.658. Phototherapy might increase urinary calcium excretion although it does not cause hypocalcemia.

  11. The effect of phototherapy on urinary calcium excretion in term neonates.

    Science.gov (United States)

    Asl, Afshin Safaei; Zarkeshl, Marjaneh; Heidarzadeh, Abtin; Maleknejad, Shohreh; Hagikhani, Kaveh

    2016-05-01

    Phototherapy is the most common, most effective, and least dangerous treatment method for neonatal hyperbilirubinemia and is the treatment of the first choice for neonatal icterus. Hypocalcemia is one of the lesser-known complications of phototherapy. Some studies have shown a relationship between increased urinary calcium excretion and phototherapy-induced hypocalcemia. We aimed to assess the effect of phototherapy on urinary calcium excretion in term neonates. This before-after study was performed on 80 term neonates having hyper- bilirubinemia referred to the 17(th) Shahrivar Hospital, Rasht, Guilan Province, Northern Iran, over a one-year period from May 2013 to May 2014. Electrocardiography was performed to measure QTc in all neonates at admission and 48 h after phototherapy. Blood and urine samples were taken from all neonates before and 48 h after phototherapy. Phototherapy was performed using four lamps with similar wavelengths from a distance of 20 cm. The serum and urinary calcium and sodium levels and urinary creatinine level before and after phototherapy were measured and compared. Data were analyzed using SPSS software, version 16. The mean age of the study subjects was 7.01 ± 4.13 days. We did not find any significant difference between urinary calcium levels (P = 0.0001), urinary creatinine levels (P = 0.954), or the calcium/creatinine ratio (P = 0.086) before and after phototherapy. The neonates' mean ± standard deviation plasma as well as urinary sodium levels differed before and after phototherapy; the difference was not statistically significant (P = 0.658). Phototherapy might increase urinary calcium excretion although it does not cause hypocalcemia. PMID:27215239

  12. Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells

    International Nuclear Information System (INIS)

    Maitotoxin (MTX) increases formation of [3H]inositol phosphates from phosphoinositides and release of [3H]arachidonic acid from phospholipids in pheochromocytoma PC12 cells. Formation of [3H]inositol phosphates is detected within 1 min of incubation even with concentrations as low as 0.3 ng/ml (90 pm) MTX, whereas release of [3H]arachidonic acid is not detected until 20 min even with concentrations as high as 1 ng/ml (300 pm) MTX. Stimulation of arachidonic acid release can be detected at 0.03 ng/ml (9 pm) MTX, whereas 0.1 ng/ml (30 pm) MTX is the threshold for detection of phosphoinositide breakdown. Organic and inorganic calcium channel blockers, except Cd2+ and a high concentration of Mn2+, have no effect on MTX-elicited phosphoinositide breakdown, whereas inorganic blockers (e.g., Co2+, Mn2+, Cd2+), but not organic blockers (nifedipine, verapamil, diltiazem), inhibit MTX-stimulated arachidonic acid release. All calcium channel blockers, however, inhibited MTX-elicited influx of 45Ca2+ and the MTX-elicited increase in internal Ca2+ measured with fura-2 was markedly reduced by nifedipine. MTX-elicited phosphoinositide breakdown and arachidonic acid release are abolished or reduced, respectively, in the absence of extracellular calcium plus chelating agent. The calcium ionophore A23187 has little or no effect alone but, in combination with MTX, A23187 inhibits MTX-elicited phosphoinositide breakdown and enhances arachidonic acid release, the latter even in the absence of extracellular calcium. The results suggest that different sites and/or mechanisms are involved in stimulation of calcium influx, breakdown of phosphoinositides, and release of arachidonic acid by MTX

  13. Effects of calcium magnesium acetate on the combustion of Coal-Water Slurry

    Energy Technology Data Exchange (ETDEWEB)

    Levendis, Y.A.

    1990-01-01

    The general objective of the project is to investigate the combustion behavior of single and multiple Coal-Water Slurry particles burning at high temperature environments. Both uncatalyzed as well as catalyzed CWS drops with Calcium Magnesium Acetate (CMA) catalyst will be investigated. Emphasis will also be given in the effects of CMA on the sulfur capture during combustion.

  14. Effect of prebiotic supplementation and calcium intake on body mass index

    Science.gov (United States)

    Our objective was to assess the effects of a prebiotic supplement and usual calcium intake on body composition changes during pubertal growth. We measured anthropometry and body fat with dual-energy X-ray absorptionmetry in 97 young adolescents who were randomized to receive either a daily prebiotic...

  15. Effect of an oily calcium hydroxide suspension on early wound healing after nonsurgical periodontal therapy.

    NARCIS (Netherlands)

    Kasaj, A.; Willershausen, B.; Berakdar, M.; Tekyatan, H.; Sculean, A.

    2006-01-01

    The purpose of the present study was to evaluate clinically the effect of an oily calcium hydroxide suspension on early wound healing after nonsurgical periodontal therapy. A total of 19 patients with chronic periodontitis were enrolled in the study. Each subject had three sites in each of two contr

  16. Effects of irrigation solutions and Calcium hydroxide dressing on root canal treatments of periapical lesions

    Directory of Open Access Journals (Sweden)

    Vita Nirmala

    2006-03-01

    Full Text Available The preparation of root canal in endodontic treatment plays an important role in treating non vital teeth with periapical lesion. Some factors influence the success of root canal treatment in short and long terms are the irrigation of root canal using antiseptic solution and the use of root canal medicament. The aim of this literature study is to determined the effect of irrigation solution and Calcium hydroxide dressing in root canal treatment of periapical lesions. The use of root canal medicament during the endodontic treatment could sterilized and decreased the number of pathogenic microorganism of root canal. An effective root canal irrigation solution must be able to dissolve organic and anorganic debris, lubricate endodontic instruments, disinfect microorganisms, non toxic and economical. The best irrigation solution has maximum antimicrobial effect with minimum toxicity. Division of calcium hydroxide into Calcium and hydroxyl ions is responsible for alkalinization of cavity, subsequently it makes the condition of cavity to be inappropriate for bacterial endotoxin in vitro as well as in vivo, and considered as the only clinically effective medicament in inactivating bacterial endotoxin. Calcium hydroxide is the only medication which has the ability to clinically inactive bacterial endotoxin in vitro in vivo and accepted as the best of root canal medication.

  17. The effects of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts

    NARCIS (Netherlands)

    Yang, Liang; Perez-Amodio, Soledad; Barrere-de Groot, Florence Y.F.; Everts, Vincent; Blitterswijk, van Clemens A.; Habibovic, Pamela

    2010-01-01

    This study describes a medium-throughput system based on deposition of calcium phosphate films in multi-well tissue culture plates that can be used to study the effect of inorganic additives on the behavior of osteoblasts and osteoclasts in a standardized manner. All tested elements, copper, zinc, s

  18. Effect of Calcium Additive on the Crystallization of Struvite

    Directory of Open Access Journals (Sweden)

    Perwitasari Dyah Suci

    2016-01-01

    Full Text Available Crystallization of struvite [MgNH4PO4.6H2O] may lead to the deposition of scale which may create significant problems in the process pipes, pumps and other industrial equipment. However, struvite precipitation can be benefited for phosphate recovery for use of fertilizer. The aim at the present work was to investigate calcium additive on struvite precipitation. The experiment was carried out in a batch mode using a 1-liter Pyrex glass vessel mechanically agitated for 200 rpm. The scale-forming solution was prepared for mixing solutions to MgCl2 and NH4H2PO4 with Mg+2 , NH4+ and PO4-3 in a molar ratio of 1: 1:1. The crystallization temperature of 30 and 40 °C was selected. Ca was added into the crystallizing solution to chloride dihydrate 0.4M (CaCl2•2H2O. Then each solution was pH adjusted to 9 by addition of KOH. The crystals obtained were characterized using SEM for morphology, EDS for elemental analysis as well as XRPD Rietveld analysis for crystaline phases. The induction periods varied from 10 to 90 min, which means that the struvite crystals began forming 10 to 90 min after mixing of the solution. It was observed that the Ca additive may inhibit the struvite crystallization. SEM analysis revealed that the struvite crystals obtained were predominantly of irregular prismatic morphology. Furthermore, the EDS pattern revealed that the elemental composition of the crystals consisted of Ca, Cl, S Mg, N, and P, providing that many crystalline phase found in the crystals such as Gypsum, CaCl2, struvite, struvite-(K and sylvite. It was observed that the Ca additive appeared to inhibit the struvite crystallization.

  19. Elucidating the Effect of Biomolecule Structure on Calcium Carbonate Crystal Formation

    Science.gov (United States)

    Kulbok, K. E.; Duckworth, O.

    2011-12-01

    Anthropogenic emissions of carbon dioxide have lead to a steady increase in atmospheric concentration. This greenhouse gas has been identified as a key driver of climate change and also has lead to increased acidification of marine and terrestrial waters. Calcium carbonate precipitation at the Earth's surface is an integral linkage in the global carbon cycle, especially in regards to regulating atmospheric carbon dioxide. As concern for the effect of increasing atmospheric CO2 levels grows, the need to understand calcium carbonate systems escalates concurrently. Calcium carbonate phases are the most abundant group of biominerals; therefore, elucidating the mechanism of biomineralization is critical to understanding CaCO3 precipitation and may aid in the development of novel carbon sequestration strategies. The ubiquity of microorganisms leads to an extensive number of biomolecules present in the Earth's systems, and thus an extensive range of possible effects on CaCO3 formation. Carboxylic acids are very common biomolecules and have a relatively simple structure, thus making them an ideal family of model compounds. This study examines the kinetics, thermodynamics, phase, and morphology of calcium carbonate crystals precipitated in the presence of carboxylate-containing biomolecules, including citric acid, succinic acid, and aspartic acid. The experiments utilize a unique (NH4)2CO3 gas-diffusion reactor, which allows in-situ measurements of chemical conditions during the precipitation and growth of crystals. Continuous monitoring of the in-situ conditions of pCO2, pH, [Ca2+], and optical absorbance provides data on the supersaturation at which nucleation occurs and the kinetics of mineral growth. The use of scanning electron microscopy and X-ray diffraction provides information on the morphology and mineralogy of precipitates. The combination of these data sets will provide an in-depth view of the ideal concentration of calcium ions required for solution saturation

  20. Nanoscale observations of the effect of citrate on calcium oxalate precipitation on calcite surfaces.

    Science.gov (United States)

    Burgos-Cara, Alejandro; Ruiz-Agudo, Encarnacion; Putnis, Christine V.

    2016-04-01

    Calcium oxalate (CaC2O4ṡxH2O) minerals are naturally occurring minerals found in fossils, plants, kidney stones and is a by-product in some processes such as paper, food and beverage production [1,2]. In particular, calcium oxalate monohydrate phase (COM) also known as whewellite (CaC2O4ṡH2O), is the most frequently reported mineral phase found in urinary and kidney stones together with phosphates. Organic additives are well known to play a key role in the formation of minerals in both biotic and abiotic systems, either facilitating their precipitation or hindering it. In this regard, recent studies have provided direct evidence demonstrating that citrate species could enhance dissolution of COM and inhibit their precipitation. [3,4] The present work aims at evauate the influence of pH, citrate and oxalic acid concentrations in calcium oxalate precipitation on calcite surfaces (Island Spar, Chihuahua, Mexico) through in-situ nanoscale observation using in situ atomic force microscopy (AFM, Multimode, Bruker) in flow-through experiments. Changes in calcium oxalate morphologies and precipitated phases were observed, as well as the inhibitory effect of citrate on calcium oxalate precipitation, which also lead to stabilization an the amorphous calcium oxalate phase. [1] K.D. Demadis, M. Öner, Inhibitory effects of "green"additives on the crystal growth of sparingly soluble salts, in: J.T. Pearlman (Ed.), Green Chemistry Research Trends, Nova Science Publishers Inc., New York, 2009, pp. 265-287. [2] M. Masár, M. Zuborová, D. Kaniansky, B. Stanislawski, Determination of oxalate in beer by zone electrophoresis on a chip with conductivity detection, J. Sep. Sci. 26 (2003) 647-652. [3] Chutipongtanate S, Chaiyarit S, Thongboonkerd V. Citrate, not phosphate, can dissolve calcium oxalate monohydrate crystals and detach these crystals from renal tubular cells. Eur J Pharmacol 2012;689:219-25. [4] Weaver ML, Qiu SR, Hoyer JR, Casey WH, Nancollas GH, De Yoreo JJ

  1. Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer

    Directory of Open Access Journals (Sweden)

    Milton Carlos KUGA

    2014-06-01

    Full Text Available Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. Objective: The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF or containing 5% (MTAF5 or 10% (MTAF10 calcium hydroxide (CH, in weight, in comparison with AH Plus sealer. Material and Methods: The flowability test was performed according to the ISO 6876:2001 requirements. For the pH level and calcium ion release analyses, the sealers were placed individually (n=10 in plastic tubes and immersed in deionized water. After 24 hours, 7 and 14 days, the water in which each specimen had been immersed was evaluated to determine the pH level changes and calcium released. Flowability, pH level and calcium release data were analyzed statistically by the ANOVA test (α=5%. Results: In relation to flowability: MTAF>AH Plus>MTAF5>MTAF10. In relation to the pH level, for 24 h: MTAF5=MTAF10=MTAF>AH Plus; for 7 and 14 days: MTAF5=MTAF10>MTAF>AH Plus. For the calcium release, for all periods: MTAF>MTAF5=MTAF10>AH Plus. Conclusions: The addition of 5% CH to the MTA Fillapex (in weight is an alternative to reduce the high flowability presented by the sealer, without interfering in its alkalization potential.

  2. Estimation of the cost-effectiveness of apixaban versus vitamin K antagonists in the management of atrial fibrillation in Argentina.

    Science.gov (United States)

    Giorgi, Mariano Anibal; Caroli, Christian; Giglio, Norberto Damian; Micone, Paula; Aiello, Eleonora; Vulcano, Cristina; Blanco, Julia; Donato, Bonnie; Quevedo, Joaquin Mould

    2015-12-01

    Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer's perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 - 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina.

  3. Estimation of the cost-effectiveness of apixaban versus vitamin K antagonists in the management of atrial fibrillation in Argentina.

    Science.gov (United States)

    Giorgi, Mariano Anibal; Caroli, Christian; Giglio, Norberto Damian; Micone, Paula; Aiello, Eleonora; Vulcano, Cristina; Blanco, Julia; Donato, Bonnie; Quevedo, Joaquin Mould

    2015-12-01

    Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer's perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 - 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina. PMID:26112219

  4. Antagonist effect of Interleukin 1 receptor on normal thymopoiesis and thymus toxicity of 5-azacytidine in mouse

    Science.gov (United States)

    Yu, Hongjing; Wu, Mingyuan; Wen, Bin; Sun, Ningyun; Xiang, Di; Zhang, Jing; Zhu, Shunying; Weng, Shunyan; Yu, Yan; Han, Wei

    2016-01-01

    Thymopoiesis is essential and significant for development and maintenance of the robust and healthy immune system. The acute suppression of thymopoiesis induced by 5-Azacytidine (5-Aza) is an intractable clinical problem complicating chemotherapy. Interleukin 1 receptor antagonist (IL-1Ra) is a cytokine that competitively blocks binding of interleukin 1 (IL-1) to its receptor. This study aims to investigate the effects of the IL-1Ra on the thymus toxicity of 5-Aza in mouse. In this study, we treated the mice with the 5-Aza (100 mg/kg per mouse). The GeneChip methodology developed by Affymetrix was used to monitor global gene expression during mouse thymus regeneration induced by a single injection of 5-Aza. The total thymocytes were counted using a hemocytometer. Cell cycle of samples were analyzed on a Becton Dickinson FACScan. Cells surfaces were labeled with anti-CD4, anti-CD8 and anti-CD45RA antibodies, and detected by flow cytometry. BrdU incorporation was detected by flow cytometry. The results indicated that administering exogenous IL-1Ra to normal mice inhibited cell cycle progress of thymocytes in a dosage-dependent manner. Proliferation of immature CD4-CD8- double negative (DN) and CD4+CD8+ double positive (DP) thymocytes were both inhibited. The pretreatment of normal mice with exogenous IL-1Ra reduced acute toxicity on thymus and immune suppression induced by 5-Aza. Furthermore, thymus reconstitution after 5-Aza treatment was accelerated by IL-1Ra. In conclusion, interleukin 1 receptor antagonist could inhibit normal thymopoiesis and reduce thymus toxicity of 5-azacytidine in mouse. Pretreatment with IL-1Ra would offer a new and promising strategy to alleviate immunotoxicity of chemotherapy in clinical. PMID:27158410

  5. Antagonist effect of Interleukin 1 receptor on normal thymopoiesis and thymus toxicity of 5-azacytidine in mouse.

    Science.gov (United States)

    Yu, Hongjing; Wu, Mingyuan; Wen, Bin; Sun, Ningyun; Xiang, Di; Zhang, Jing; Zhu, Shunying; Weng, Shunyan; Yu, Yan; Han, Wei

    2016-01-01

    Thymopoiesis is essential and significant for development and maintenance of the robust and healthy immune system. The acute suppression of thymopoiesis induced by 5-Azacytidine (5-Aza) is an intractable clinical problem complicating chemotherapy. Interleukin 1 receptor antagonist (IL-1Ra) is a cytokine that competitively blocks binding of interleukin 1 (IL-1) to its receptor. This study aims to investigate the effects of the IL-1Ra on the thymus toxicity of 5-Aza in mouse. In this study, we treated the mice with the 5-Aza (100 mg/kg per mouse). The GeneChip methodology developed by Affymetrix was used to monitor global gene expression during mouse thymus regeneration induced by a single injection of 5-Aza. The total thymocytes were counted using a hemocytometer. Cell cycle of samples were analyzed on a Becton Dickinson FACScan. Cells surfaces were labeled with anti-CD4, anti-CD8 and anti-CD45RA antibodies, and detected by flow cytometry. BrdU incorporation was detected by flow cytometry. The results indicated that administering exogenous IL-1Ra to normal mice inhibited cell cycle progress of thymocytes in a dosage-dependent manner. Proliferation of immature CD4(-)CD8(-) double negative (DN) and CD4(+)CD8(+) double positive (DP) thymocytes were both inhibited. The pretreatment of normal mice with exogenous IL-1Ra reduced acute toxicity on thymus and immune suppression induced by 5-Aza. Furthermore, thymus reconstitution after 5-Aza treatment was accelerated by IL-1Ra. In conclusion, interleukin 1 receptor antagonist could inhibit normal thymopoiesis and reduce thymus toxicity of 5-azacytidine in mouse. Pretreatment with IL-1Ra would offer a new and promising strategy to alleviate immunotoxicity of chemotherapy in clinical. PMID:27158410

  6. [Effect of excitant amino acid antagonists on glutamate receptors in the locust and on convulsions induced by glutamate, aspartate, kynurenine and quinolinic acid in mice].

    Science.gov (United States)

    Ryzhov, I V; Slepokurov, M V; Lapin, I P; Mandel'shtam, Iu E; Aleksandrov, V G

    1986-03-01

    All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites. PMID:2869799

  7. Effect of Calcium Oxide Additive on the Performance of Iron Oxide Sorbent for High-Temperature Coal Gas Desulfurization

    Institute of Scientific and Technical Information of China (English)

    Huiling Fan; Kechang Xie; Ju Shangguan; Fang Shen; Chunhu Li

    2007-01-01

    The effect of calcium oxide additive in iron oxide sorbent for hot gas desulfurization was investigated by XRD and TPR techniques. XRD characterization showed that CaO was highly dispersed after the calcination of sorbents. Calcium sulfate formed in the desulfurization was decomposed and regenerated to CaO by reacting with CO before the next sulfidation process. Calcium participated in every sulfidation/regeneration cycle and contributed to the enhancement of sulfur capacity. The TPR results showed that the reduction temperature of the sorbent increased with the increase of the content of calcium. Calcium played a role of retarding reduction. Therefore, the addition of calcium oxide additive will benefit the utilization of iron oxide sorbent in strongly reducing atmospheres.

  8. Effects of particle size, slice thickness, and reconstruction algorithm on coronary calcium quantitation using ultrafast computed tomography

    Science.gov (United States)

    Tang, Weiyi; Detrano, Robert; Kang, Xingping; Garner, D.; Nickerson, Sharon; Desimone, P.; Mahaisavariya, Paiboon; Brundage, B.

    1994-05-01

    The recent emphasis on early diagnosis of coronary artery disease has stimulated research for a reliable and non-invasive screening method. Radiographically detectable coronary calcium has been shown to predict both pathologic and angiographic findings. Ultrafast computed tomography (UFCT), in quantifying coronary calcium, may become an accurate non-invasive method to evaluate the severity of coronary disease. The currently applied index of UFCT coronary calcium amount is the coronary calcium score of Agatston et al. This score has not been thoroughly evaluated as to its accuracy and dependence on scanning parameters. A potential drawback of the score is its dependence on predetermined CT number thresholds. In this investigation we used a chest phantom to determine the effects of particle size, slice thickness, and reconstruction algorithm on the coronary calcium score, and on the calcium mass estimated with a new method which is not dependent on thresholds.

  9. Effects of temperature and sodium carboxylate additives on mineralization of calcium oxalate in silica gel systems

    Institute of Scientific and Technical Information of China (English)

    OUYANG; Jianming; DENG; Suiping; LI; Xiangping; TAN; Yanh

    2004-01-01

    [1]Ouyang, J. M., Yao, X. Q., Su, Z. X. et al., Simulation of calcium oxalate stone in Vitro, Science in China, Ser. B, 2003, 46(3):234-242.[2]Xu, S. H., Chen, J. Q., Zhou, H., Nepidemiological study of renal calculus in Shenshen region, Chin. J. Urol. (in Chinese), 1999,20(11): 655-657.[3]Bretherton, T., Rodgers, A., Crystallization of calcium oxalate in minimally diluted urine, J. Crystal Growth, 1998, 192: 448-455.[4]Grover, P. K., Ryall, R. L., Effect of seed crystals of uric acid and monosodium urate on the crystallization of CaOxa in undiluted human urine in vitro, Clin. Sci., 1997, 92: 205-213.[5]Laube, N., Mohr, B., Hesse, A., Laser-probe-based investigation of the evolution of particle size distributions of calcium oxalate particles formed in artificial urines, J. Crystal Growth, 2001, 233:367-374.[6]Tunik, L., Fueredi-Milhofer, H., Garti, N., Adsorption of sodium diisooctyl sulfosuccinate onto calcium oxalate crystals, Langmuir,1998, 14: 3351-3355.[7]Cody, A. M., Cody, R. D., Calcium oxalate trihydrate phase control by structurally-specific carboxylic acids, J. Cryst. Growth,1994, 135: 234-245.[8]Ouyang, J. M., Duan, L., Tieke, B., Effects of carboxylic acids on the crystal growth of calcium oxalate nanoparticles in lecithin-water liposome systems, Langmuir, 2003, 19: 8980-8985.[9]Guo, S., Ward, M. D., Wesson, J. A., Direct visualization of calcium oxalate monohydrate crystallization and dissolution with atomic force microscopy and the role of polymeric additives,Langmuir, 2002, 18:4284-4291.[10]Yasui, T., Sato, M., Fujita, K., Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model,Urol. Res., 2001,29: 50-56.[11]Ouyang, J. M., Deng, S. P., Controlled and uncontrolled crystallization of calcium oxalate monohydrate in the presence of citric acid, Dalton Transactions, 2003, (14): 2846-2851.[12]Khan, S. R., Whalen, P. O., Glenton, P. A., Heterogeneous nucleation of

  10. Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in Ophthalmic Neoangiogenesis Models

    Science.gov (United States)

    Coroniti, Roberta; Fario, Rafal; Nuno, Didier J.; Otvos, Laszlo; Scolaro, Laura; Surmacz, Eva

    2016-01-01

    Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema. Accordingly, drugs targeting VEGF are becoming mainstream treatments for these diseases. The crosstalk between leptin and VEGF has been noted in different tissues, but its involvement in the development of eye pathologies is unclear. Leptin is coexpressed with VEGF during ocular neovascularization and can potentiate VEGF synthesis and angiogenic function. However, whether or not VEGF regulates leptin expression or signaling has never been studied. Consequently, we addressed this aspect of leptin/VEGF crosstalk in ocular models, focusing on therapeutic exploration of underlying mechanisms. Here we show, for the first time, that in retinal (RF/6A) and corneal (BCE) endothelial cells, VEGF (100 ng/mL, 24 h) stimulated leptin mRNA synthesis by 70 and 30%, respectively, and protein expression by 56 and 28%, respectively. In parallel, VEGF induced RF/6A and BCE cell growth by 33 and 20%, respectively. In addition, VEGF upregulated chemotaxis and chemokinesis in retinal cells by ~40%. VEGF-dependent proliferation and migration were significantly reduced in the presence of the leptin receptor antagonist, Allo-aca, at 100–250 nmol/L concentrations. Furthermore, Allo-aca suppressed VEGF-dependent long-term (24 h), but not acute (15 min) stimulation of the Akt and ERK1/2 signaling pathways. The efficacy of Allo-aca was validated in the rat laser-induced choroidal neovascularization model where the compound (5 μg/eye) significantly reduced pathological

  11. The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

    Directory of Open Access Journals (Sweden)

    Temitayo O. Iji

    2013-02-01

    Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

  12. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects.

    Science.gov (United States)

    Sun, Hong; Yee, Ka Lai; Gill, Sean; Liu, Wen; Li, Xiaodong; Panebianco, Deborah; Mangin, Eric; Morrison, Dennis; McCrea, Jacqueline; Wagner, John A; Troyer, Matthew D

    2015-11-01

    A double-blind crossover study investigated psychomotor effects, pharmacokinetics, and safety of the orexin receptor antagonist suvorexant with and without alcohol. Healthy adults (n=31) were randomized to receive placebo or suvorexant (40 mg) plus placebo solution or alcohol (0.7 g/kg) in each of four treatments (single doses; morning administration). The US Food and Drug Administration approved suvorexant dose is 10 mg (up to 20 mg) daily. Pharmacodynamic effects were assessed using tests of digit vigilance (DVT; primary endpoint), choice reaction time, digit symbol substitution, numeric working memory, immediate/delayed word recall, body sway and subjective alertness. Suvorexant alone did not significantly affect DVT reaction time, but did impact some pharmacodynamic tests. Suvorexant with alcohol increased reaction time versus either alone (mean difference at 2 h: 44 ms versus suvorexant, p<0.001; 24 ms, versus alcohol, p<0.05) and had additive negative effects on tests of vigilance, working/episodic memory, postural stability and alertness. No effects of suvorexant alone or with alcohol were observed by 9 h. No important changes in pharmacokinetic parameters were observed upon co-administration. All treatments were generally well tolerated without serious adverse events. In conclusion, co-administration of 40 mg suvorexant and 0.7 g/kg alcohol had additive negative psychomotor effects. Patients are advised not to consume alcohol with suvorexant. PMID:26464455

  13. The interactive effects of ammonia and microcystin on life-history traits of the cladoceran Daphnia magna: synergistic or antagonistic?

    Directory of Open Access Journals (Sweden)

    Zhou Yang

    Full Text Available The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the life history of the model organism Daphnia magna. Ammonia and microcystin-LR treatments were: 0, 0.366, 0.581 mg L(-1 and 0, 10, 30, 100 µg L(-1, respectively. Experiments followed a fully factorial design. Incubations were 14 d and recorded the following life-history traits: number of moults, time to first batch of eggs, time to first clutch, size at first batch of eggs, size at first clutch, number of clutches per female, number of offspring per clutch, and total offspring per female. Both ammonia and microcystin were detrimental to most life-history traits. Interactive effects of the toxins occurred for five traits: the time to first batch of eggs appearing in the brood pouch, time to first clutch, size at first clutch, number of clutches, and total offspring per female. The interactive effects of ammonia and microcystin appeared to be synergistic on some parameters (e.g., time to first eggs and antagonistic on others (e.g., total offspring per female. In conclusion, the released toxins during the degradation of Microcystis blooms would result, according to our data, in substantially negative effect on D. magna.

  14. The Comparison of Antagonistic Effects of Normal Vaginal Lactobacilli and Some Commonly used Antibiotics on Isolated Bacteria of Uterine Infections in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Pouya Dini

    2012-12-01

    Full Text Available Uterine infections are one of the major reproductive complications during postpartum. The antibiotics and antiseptic agents used in the treatment of postpartum infections have residues in food, induce bacterial resistance, increase the financial costs and cause failure in defense mechanism of host. On the other hand, nowadays the administration of probiotics is considered as an alternative method for the prevention and treatment of infections. Therefore, preventive treatment with probiotic product could decrease the usage of antibiotic and bring advantages in dairy farm systems. The objective of this study was screening of the antagonistic properties of isolated vaginal Lactic Acid Bacteria (LAB against the most prevalent bacteria in uterine infections in order to investigate their probiotic potentials as an alternative approach for prevention of uterine infections. LAB were isolated from sampling of cranial part of vagina during estrus phase and luteal phase of Holstein dairy cattle and pathogens bacteria were isolated from merits and endometritis specimens which referred to our veterinary laboratory. The antagonistic activity of isolated LAB against uterine pathogens was tested by Agar spot test. Antibiotic susceptibilities of pathogenic strains to commonly used antibiotics were investigated by using disc diffusion method. Inhibition zones around both the probiotic spots and the antibiotic discs were classified to weak, moderate and strong categories and their antagonistic efficacies were compared. Isolated LAB had antagonistic effects against all the pathogenic strains including both gram negative and gram positive, Arcanobacterium pyogenes and Pseudomonas aeroginosa were the most sensitive bacteria (with 12.60 and 14 mm an average inhibition zone, respectively. LAB had the least antagonistic effects on Clostridium perfringens (3.6 mm of an average inhibition zone. Comparing the antagonistic efficacies, the percentages of overall

  15. The effect of the non-NMDA receptor antagonist GYKI 52466 and NBQX and the competitive NMDA receptor antagonist D-CPPene on the development of amygdala kindling and on amygdala-kindled seizures.

    Science.gov (United States)

    Dürmüller, N; Craggs, M; Meldrum, B S

    1994-02-01

    A competitive (NBQX) and a non-competitive (GYKI 52466) AMPA antagonist, and a competitive NMDA antagonist (D-CPPene) were tested against the development of kindling and against fully kindled seizures in amygdala-kindled rats. GYKI 52466, 10 mg/kg given i.p. 5 min prior to electrical stimulation in fully kindled animals, reduces both the cortical after-discharge duration and the behavioural seizure score. GYKI 52466, 20 mg/kg, reduces seizure score and after-discharge duration significantly (after 5-30 min) but the animals show severe motor side effects and an irregular cortical and hippocampal EEG. Administration of GYKI 52466, 10 mg/kg, prior to kindling stimulation on days 3-8, does not slow the development of kindling. NBQX, 20 mg/kg or 40 mg/kg i.p., 30 min prior to stimulation, significantly reduces the seizure score in fully kindled animals. NBQX 20 mg/kg i.p. has no effect on the development of kindling. D-CPPene, 8 mg/kg or 12 mg/kg, 120 min prior to stimulation reduces the behavioural seizure score in fully kindled animals. D-CPPene, 8 mg/kg on days 3-8, delays the development of kindling. NMDA receptors play a key role in the kindling process. Expression of kindled seizures involves non-NMDA and NMDA receptors.

  16. Antagonistic Pleiotropy at the Human "IL6" Promoter Confers Genetic Resilience to the Pro-Inflammatory Effects of Adverse Social Conditions in Adolescence

    Science.gov (United States)

    Cole, Steven W.; Arevalo, Jesusa M. G.; Manu, Kavya; Telzer, Eva H.; Kiang, Lisa; Bower, Julienne E.; Irwin, Michael R.; Fuligni, Andrew J.

    2011-01-01

    The authors tested the evolutionary genetic hypothesis that the functional form of an asymmetrically risky Gene x Environment interaction will differ as a function of age-related antagonistic pleiotropy (i.e., show opposite effects in young vs. old individuals). Previous studies have identified a polymorphism in the human "IL6" promoter…

  17. Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

    DEFF Research Database (Denmark)

    Borregaard, Jeanett; Skov, Lone; Wang, Lisy;

    2008-01-01

    BACKGROUND: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1. OBJECTIVES: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs and...

  18. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats.

    Science.gov (United States)

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki

    2006-08-14

    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  19. Chronic psychosocial stress in tree shrews : effect of the substance P (NK1 receptor) antagonist L-760735 and clomipramine on endocrine and behavioral parameters

    NARCIS (Netherlands)

    van der Hart, MGC; de Biurrun, G; Czeh, B; Rupniak, NMJ; den Boer, JA; Fuchs, E

    2005-01-01

    Rationale: Substance P and its preferred receptor, the neurokinin 1 receptor (NK1R), have been proposed as possible targets for new antidepressant therapies, although results of a recently completed phase III trial failed to demonstrate that the NK1R antagonist MK-869 is more effective than placebo

  20. Co-administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis

    NARCIS (Netherlands)

    Charrua, A.; Cruz, C.D.; Jansen, D.; Rozenberg, B.; Heesakkers, J.P.; Cruz, F.

    2015-01-01

    OBJECTIVE: To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis. MATERIAL AND METHODS: TRPV4 expression in bladder afferents

  1. Effect of Calcium Chloride and Cooling on Post-Harvest Brussels Cabbage (Brassica Oleracea L.

    Directory of Open Access Journals (Sweden)

    Alfonso Rincón Pérez

    2014-11-01

    Full Text Available In recent years, the demand of crucifers has increased and particularly of Brussels sprouts (Brassica genus, species Brassica oleracea L.; mainly due to their functional properties; however, this vegetable is perishable and with inadequate techniques in postharvest handling, considerable losses are generated. The objective of this research was to determine the effect of calcium chloride and cooling on postharvest behavior of Brussels sprouts. A completely randomized design was performed, treatments corresponded to three storage temperatures (4°C, 8°C and temperature (18°C and three concentrations of calcium chloride (0%, 2% and 4% were used. Sprouts were harvested at commercial maturity on a farm irrigation district in Usochicamocha, Boyacá Department; of uniform size, excellent plant health and free from mechanical damage conditions. For 19 days of storage, weight loss, respiratory rate and total chlorophyll were measured. Sprouts stored at room temperature lasted 11days postharvest, while cooled lasted for 19 days. A significant effect in reducing weight loss between those sprouts which were stored at 4°C and 8°C and treated with calcium chloride solution at 4% was observed. For the respiratory rate was observed a significant reduction insprouts stored at 4°C. Therefore the most favorable temperature for the storage of Brussels sprouts is 4°C and calcium chloride solution 4%,useful information for producers and marketers.

  2. Effects of dietary calcium, phosphorus and magnesium on intranephronic calculosis in rats.

    Science.gov (United States)

    Woodward, J C; Jee, W S

    1984-12-01

    The effects of varying dietary levels of calcium, phosphorus and magnesium on the incidence and severity of intranephronic calculosis were studied. Renal calculi were induced by feeding female rats the AIN-76TM semipurified diet for 4 weeks. During this time period, dietary levels of 350, 450 or 550 mg calcium per 100 g diet did not influence the occurrence of urolithiasis. Increasing dietary magnesium levels from 50 to 350 mg was beneficial in preventing the occurrence of calculi if the diet contained 400 mg or less phosphorus. The protective effects of dietary magnesium were counteracted when dietary phosphorus levels were increased from 400 mg to 550 or 700 mg. If the dietary content of phosphorus and magnesium permitted the formation of renal calculi, the severity of the condition was also influenced by the dietary level of calcium. Some animal groups fed semipurified diets did not have microscopic or radiographic evidence of renal calculi but were found to have significantly elevated renal calcium values. It was suggested that these animals might be in a precalculus-forming state. PMID:6502276

  3. Differential effects of arsenic on calcium signaling in primary keratinocytes and malignant (HSC-1) cells.

    Science.gov (United States)

    Hsu, W L; Tsai, M H; Lin, M W; Chiu, Y C; Lu, J H; Chang, C H; Yu, H S; Yoshioka, T

    2012-08-01

    Arsenic is highly toxic to living cells, especially skin, and skin cancer is induced by drinking water containing arsenic. The molecular mechanisms of arsenic-induced cancer, however, are not well understood. To examine the initial processes in the development of arsenic-induced cancer, we analyzed calcium signaling at an early stage of arsenic treatment of human primary cells and compared the effects with those observed with arsenic treatment in carcinoma-derived cells. We found that arsenic inhibited inositol trisphosphate receptor (IP3R) function in the endoplasmic reticulum by inducing phosphorylation, which led to decreased intracellular calcium levels. Blockade of IP3R phosphorylation by the serine/threonine protein kinase Akt inhibitor wortmannin rescued calcium signaling. In contrast, arsenic treatment of cells derived from a carcinoma (human squamous carcinoma; HSC-1) for 1h had no obvious effect. Taken together, these results suggest that arsenic-induced reduction in calcium signaling is one of the initial mechanisms underlying the malignant transformation in the development of skin cancer.

  4. The effect of calcium and phosphorus supplementation on metabolic bone disorders in premature infants

    International Nuclear Information System (INIS)

    Objective: To determine the impact of calcium and phosphorus on radiological and biochemical characteristics of osteopenia in premature infants. Methods: The randomised clinical trial study was conducted at Valie-e-Asr Hospital of Zanjan city, Iran, from December 2010 to June 2011. It involved monitoring 40 premature neonates over a period of six months. The babies, who were fed with breast milk and 400 units of vitamin D daily, were randomly divided into two equal groups. One group received supplement of calcium and phosphorus. Serum calcium, phosphorus and alkaline phosphatase levels as well as growth parameters (including weight, height, and head circumference) were measured every two weeks. At the end of the study, wrist X-ray was done for evaluation of osteopenia. Data was analysed using SPSS 16. Results: Radiological changes, characteristic of osteopenia, were found in 8(40%) cases and 13(65%) controls (p<0.113). The mean of weight, length and head circumference increased significantly from second to sixth week during follow-up (p<0.0001). Phosphorus and alkaline phosphatase activity decreased significantly from second to sixth week of follow-up (p<0.02, p<0.01 respectively). However, repeated measurement analyses did not show significant effect of intervention in biochemical and growth parameters in the trial group. Conclusion: The study didn't show significant effect of calcium and phosphorus on prevention of osteopenia and improvement of growth. Further studies of longer duration and with different doses of supplement are recommended. (author)

  5. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects.

    Science.gov (United States)

    Sun, Hong; Yee, Ka Lai; Gill, Sean; Liu, Wen; Li, Xiaodong; Panebianco, Deborah; Mangin, Eric; Morrison, Dennis; McCrea, Jacqueline; Wagner, John A; Troyer, Matthew D

    2015-11-01

    A double-blind crossover study investigated psychomotor effects, pharmacokinetics, and safety of the orexin receptor antagonist suvorexant with and without alcohol. Healthy adults (n=31) were randomized to receive placebo or suvorexant (40 mg) plus placebo solution or alcohol (0.7 g/kg) in each of four treatments (single doses; morning administration). The US Food and Drug Administration approved suvorexant dose is 10 mg (up to 20 mg) daily. Pharmacodynamic effects were assessed using tests of digit vigilance (DVT; primary endpoint), choice reaction time, digit symbol substitution, numeric working memory, immediate/delayed word recall, body sway and subjective alertness. Suvorexant alone did not significantly affect DVT reaction time, but did impact some pharmacodynamic tests. Suvorexant with alcohol increased reaction time versus either alone (mean difference at 2 h: 44 ms versus suvorexant, palcohol, peffects on tests of vigilance, working/episodic memory, postural stability and alertness. No effects of suvorexant alone or with alcohol were observed by 9 h. No important changes in pharmacokinetic parameters were observed upon co-administration. All treatments were generally well tolerated without serious adverse events. In conclusion, co-administration of 40 mg suvorexant and 0.7 g/kg alcohol had additive negative psychomotor effects. Patients are advised not to consume alcohol with suvorexant.

  6. Effects of mu and kappa opioid receptor agonists and antagonists on contraction of isolated colon strips of rats with cathartic colon

    Institute of Scientific and Technical Information of China (English)

    Bao-Hua Liu; Ping Mo; Sheng-Ben Zhang

    2004-01-01

    AIM: To study the effects of mu and kappa opioid receptor agonists and antagonists on the isolated colon strips of rats with cathartic colon.METHODS: Cathartic colon model was established by feeding rats with contact laxatives, and effects of mu and kappaopioid receptor agonists and antagonists on electricitystimulated contraction of isolated colon strips of rats with cathartic colon were observed.RESULTS: Compared with control group, exogenous mu and kappa agonists inhibited significantly electricity-stimulated contraction of strips of cathartic colon (8.50±0.89 mm,6.24±0.91 mm, 3.35±0.6 mm vs 11.40±0.21 mm P<0.01;8.98±0.69 mm, 6.89±0.71 mm, 4.43±0.99 mm vs 11.40±0.21mm, P<0.01). In contrast, the exogenous mu antagonist significantly enhanced electricity-stimulated contraction of isolated colon strips (13.18±0.93 mm, 15.87±0.98 mm,19.46±1.79 mm vs 11.40±0.21 mm, P<0.01), but kappa antagonist had no effect on the isolated colon strips of rats with cathartic colon.

  7. The Antagonistic Effect of Selenium on Lead Toxicity Is Related to the Ion Profile in Chicken Liver.

    Science.gov (United States)

    Xu, Tong; Gao, Xuejiao; Liu, Guowen

    2016-02-01

    The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, limited data are available regarding the effects of Se on Pb and the ion profile in chicken liver. Whether the change in the ion profile was involved in the protective process of Se and the toxic effect of Pb is unknown. In the present study, we detected 26 ion profiles (including those of Na, Mg, K, Ca, B, Si, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Sb, Ba, Tl, Li, Al, As, Cd, Sn, Hg, and Pb) in chicken liver following treatment with Se or Pb and with the compound treatment of Se and Pb. The results showed that Se supplementation decreased the content of B and Cr and increased that of Zn and Ba (P Cu, Se, Mo, and Hg and increased V, Fe, Cd, and Sn (P Cu and Mn. The results also indicated that there existed both synergistic and antagonistic interactions between different ions, further verifying the principal component analysis. Thus, the results showed that prolonged exposure to Se and Pb influences the ion profiles in chicken liver. The protective role of Se and toxic effect of Pb may be related to these changing ion profiles in chicken liver. PMID:26123166

  8. Effect of Vitamin K Intake on the Stability of Treatment with Vitamin K Antagonists: A Systematic Review of the Literature.

    Science.gov (United States)

    Dentali, Francesco; Crowther, Mark; Galli, Matteo; Pomero, Fulvio; Garcia, David; Clark, Nathan; Spadafora, Laura; Witt, Daniel M; Ageno, Walter

    2016-09-01

    Vitamin K antagonists (VKA) are highly effective for the primary and secondary prevention of arterial and venous thromboembolic events. However, patients treated with VKA have on average only 60% of their international normalized ratio (INR) values within the therapeutic range and INR instability is associated with an increased risk of thrombosis and bleeding events. Recent evidence suggests that poor dietary vitamin K intake may affect anticoagulation control, but the role of vitamin K in INR stability remains to be established. We performed a systematic review of the literature to assess the role of vitamin K dietary intake on the stability of VKA and the potential effect of daily vitamin K supplementation on VKA therapy. After a search in Medline and EMBASE databases, 15 studies for a total of 1,838 patients were included in our systematic review. Observational studies suggest an increased risk of unstable anticoagulation control in patients with lower daily vitamin K intake. On the other hand, the role of daily vitamin K supplementation or a diet with controlled vitamin K content in patients on VKA treatment remains to be established. Use of daily vitamin K supplementation may be associated with a clinically relevant increase in the time in therapeutic range in patients with unstable anticoagulation control. Conversely, this effect appears small and not clinically relevant when vitamin K was administered to an unselected population receiving VKA. Other large prospective studies are necessary to confirm our preliminary findings.

  9. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

    Science.gov (United States)

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

    2009-04-01

    The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals. PMID:19036859

  10. Assessment of Effect of Angiotensin Ⅱ Receptor Antagonist Losartan on Aortic Distensibility in Patients With Essential Hypertension by Echocardiography

    Institute of Scientific and Technical Information of China (English)

    杨好意; 邓又斌; 黎春蕾; 毕小军; 潘敏; 常青

    2002-01-01

    Summary: The effects of angiotensin Ⅱ receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibili-ty in 26 patients (48± 3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardio graphy. M-mode measurements of aortic systolic (Ds) and diastolic diameter (Dd) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP)and diastolic(DBP) pressures were measured. Aortic pressure-strain elastic modulus (Ep) was calcu lated as Dd × (SBP-DBP)/(Ds-Dd) × 1333 and stiffness index beta (β) was defined as Dd × Ln (SBP/DBP)/(Ds-Dd). Blood pressure significantly decreased from 148±13/95±9 mmHg to 138± 12/88±8 mmHg (systolic blood pressure, P=0. 001; diastolic blood pressure, P=0. 003). Therewas no significant difference in pulse pressure before and after treatment with losartan (53±10 mmHg vs 50± 7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42± 5.79 × 106 dynes/cm2 to 1.99 ± 1.49 × 106 dynes/cm2 (P=0. 02) and stiffness index beta from 27.4 ± 32.9 to 13.3 ± 9.9 (P = 0. 02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment (r= 0. 40, P = 0. 04 and r = 0.55, P = 0. 004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r = 0. 04, P = 0. 8 and r = 0. 24, P = 0. 2, respectively). Our study demonstrated that angiotensin Ⅱ receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential

  11. Effect of QMix, peracetic acid and ethylenediaminetetraacetic acid on calcium loss and microhardness of root dentine

    Directory of Open Access Journals (Sweden)

    Sonali Taneja

    2014-01-01

    Full Text Available Objectives: The objective of this in vitro study was to assess the effect of different chelating agents on the calcium loss and its subsequent effect on the microhardness of the root dentin. Materials and Methods: Ten single rooted lower premolars were selected. The teeth were decoronated and thick transverse sections of 2 mm were obtained from the coronal third of the root. Each section was then divided into four quarters, each part constituting a sample specimen from the same tooth for each group. The treatment groups were: Group 1 (Control: 5% Sodium hypochlorite (NaOCl for 5 min + distilled water for 5 min; Group 2: 5% NaOCl for 5 min + 17% ethylenediaminetetraacetic acid (EDTA for 5 min; Group 3: 5% NaOCl for 5 min + 2.25% Peracetic acid (PAA for 5 min and Group 4: 5% NaOCl for 5 min + QMix for 5 min respectively. The calcium loss of the samples was evaluated using the Atomic Absorption Spectrophotometer followed by determination of their microhardness using Vickers Hardness Tester. Data was analyzed using one-way ANOVA, Post hoc Tukey test and Pearson correlation. Results: The maximum calcium loss and minimum microhardness was observed in Group 3 followed by Group 2, Group 4 and Group 1. There was a statistically significant difference between all the groups except between Groups 2 and 4. Conclusions: Irrigation with NaOCl + 2.25% PAA caused the maximum calcium loss from root dentin and reduced microhardness. A negative correlation existed between the calcium loss and reduction in the microhardness of root dentin.

  12. An interventional study (calcium supplementation & health education on premenstrual syndrome - effect on premenstrual and menstrual symptoms

    Directory of Open Access Journals (Sweden)

    Shailesh Sutariya, Nitiben Talsania, Chintul Shah, Mitesh Patel

    2011-01-01

    Full Text Available The study was conducted to study the effect of calcium supplementation on Premenstrual and Menstrual Symptoms. It was a one year follow-up prospective, randomized controlled interventional study. After the initial 2-cycle screening phase, a total of 215 healthy premenopausal women were enrolled in the study group calcium supplementation(500 BD of the trial and 140 subjects either the relatives or neighbors of the study population were enrolled as control group health, nutrition, hygiene education of the trial. By the second and third treatment months, all symptoms except for fatigue and insomnia showed a significant response to calcium. For the symptom of low backache, the mean screening score was significantly higher than the control group score (0.82±0.74 vs 0.69±0.66,p=0.033 and became significantly lower than the control group score by the end of third treatment cycle. (0.30±0.45 vs 0.49±0.59,p<0.01. Nearly half (55% of the women in the study group reported ?50% improvement and one-third (30% of the women in study group reported ?75% improvement. Significantly lower symptoms score was detected in the urban sites during the first treatment phase with calcium and during the final treatment phase

  13. Effects of inositol trisphosphate on calcium mobilization in high-voltage and saponin-permeabilized platelets

    International Nuclear Information System (INIS)

    Interest in phosphatidylinositol metabolism has been greatly stimulated by the findings that diglyceride and inositol phosphates may serve as second messengers in modulating cellular function. Formation of 1,4,5-inositol trisphosphate (IP3), in particular, has been linked to mobilization of intracellular calcium in a number of cell types. The authors have examined the ability of IP3 to mobilize calcium in human platelets permeabilized by either saponin or high-voltage discharge. Saponin at 15 μg/ml effectively permeabilized platelets to exogenous inositol 1,4,5-trisphosphate which released bound [45Ca] within 1 min and with a Ka of 7.4 +/- 4.1 μM. A small (25%) azide-sensitive pool was also responsive to inositol trisphosphate. The calcium pools were completely discharged by A-23187 and the ATP-dependent uptake was prevented by dinitrophenol. In contrast to the result with saponin, platelets accessed by high-voltage discharge were insensitive to challenge by inositol 1,4,5-trisphosphate. The data suggest that while inositol 1,4,5-trisphosphate can rapidly mobilize platelet calcium, the ability to demonstrate this depends on the method of permeabilization

  14. Endoplasmic reticulum stress in pathogenesis of diabetic retinopathy and effect of calcium dobesilate

    Institute of Scientific and Technical Information of China (English)

    Yu-Min Gui; Ming Zhao; Jie Ding

    2016-01-01

    Objective:To study the mechanism of endoplasmic reticulum stress in the pathogenesis of diabetic retinopathy and effect of calcium dobesilate.Methods:A total of 120 diabetic retinopathy patients treated in our hospital from January 2010 to September 2015 were enrolled in this article. The serum endoplasmic reticulum stress protein and interleukin protein expression levels were analyzed before and after calcium dobesilate treatment. A total of 55 cases of healthy subjects receiving physical examination in our hospital during the same period were taken as control group.Results:Serum endoplasmic reticulum stress proteins PERK, CHOP and IRE as well as interleukin proteins IL1, IL2, IL6 and IL10 expression significantly increased, serum MDA level significantly increased while SOD, CAT and GSHpx levels significantly decreased in diabetic retinopathy patients, and compared with control group (P<0.01); after calcium dobesilate treatment, above factors were significantly restored (P<0.01).Conclusions: Diabetic retinopathy is closely related to endoplasmic reticulum stress and calcium dobesilate treatment may improve diabetic retinopathy by inhibiting endoplasmic reticulum stress.

  15. Effects of Calcium Dobesilate on Glomerulus TIMP1 and Collagen Ⅳ of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    DONG Junwu; LIU Xiaochen; LIU Shenwei; LI Mingbo; XU Yanmei; CUI Bing

    2005-01-01

    To observe the effects of calcium dobesilate on the expression of glomerular tissue inhibitor of metalloproteinase 1 (TIMP1), collagen Ⅳ, and ultrastructure of glomerular basement membrane in diabetic rats, rats model of diabetes was established by unilateral nephrectomy and intraperitoneal injection of 1% STZ (55 mg/kg), and rats were administered calcium dobesilate 100 mg/kg (DD group) or distilled water (DM group) respectively. 12 weeks later, the changes in the renal ultrastructure and creatinine clearance rate (Ccr) were examined in each group. The expression of glomerular TIMP1 and collagen Ⅳ were studied by immunohistochemical staining. Our results showed that after 12 weeks, the Ccr in DD group increased and was significantly higher than that in DM group. Electron microscopy showed that thickness of glomerular capillary basement membrane (GBM) in Group DD was less than that of DM group. No hyperplasia of collagen fibers was found, and the distance between the holes of endothelial cells in DD group was not as even as that in the normal group, but more even than that of DM group, and podocyte processes was still in order. Immunohistochemical staining of glomeruli showed that expression of TIMP1 and collagen Ⅳ in DD group were significantly less than those of DM group DM. It is concluded that calcium dobesilate can improve diabetic nephropathy by inhibiting the over- accumulation of collagen Ⅳ and calcium dobesilate may also contribute to diabetes by inhibiting the expression of TIMP1.

  16. Effect of temperature on kinetic parameters of decomposition reaction of calcium carbonate

    Institute of Scientific and Technical Information of China (English)

    CHEN Hongwei; CHEN Jiangtao; WEI Riguang; SUO Xinliang

    2013-01-01

    In order to investigate the influence of temperature on behavior of calcium carbonate decomposition,especially on kinetic parameters of the decomposition reaction,the analytically pure calcium carbonate was calcined on a self-built large dose thermogravimetric analyzer.The results indicated that,with an increase in the reaction temperature,the reactivity index of calcium carbonate decomposition increased at stage state while the kinetic parameters decreased at stage state.Moreover,both the reaction indices and the kinetic parameters can be divided into three stages and the temperature turning points in different stages were the same.The phase boundary reaction (cylindrical symmetry) theory was more suitable for calcium carbonate calcination under N2 atmosphere.The change trend of the logarithm of reaction activation with temperature was similar as that of the pre-exponential factor.There existed good liner relationship and kinetic compensation effect between them.The isokinetic temperature of the CaCO3 calcination was 842 ℃ and the reaction rate constant was 0.104 9 min-1 derived by the compensation coefficients.

  17. Effect of chemical admixtures on properties of high-calcium fly ash geopolymer

    Science.gov (United States)

    Rattanasak, Ubolluk; Pankhet, Kanokwan; Chindaprasirt, Prinya

    2011-06-01

    Owing to the high viscosity of sodium silicate solution, fly ash geopolymer has the problems of low workability and rapid setting time. Therefore, the effect of chemical admixtures on the properties of fly ash geopolymer was studied to overcome the rapid set of the geopolymer in this paper. High-calcium fly ash and alkaline solution were used as starting materials to synthesize the geopolymer. Calcium chloride, calcium sulfate, sodium sulfate, and sucrose at dosages of 1wt% and 2wt% of fly ash were selected as admixtures based on concrete knowledge to improve the properties of the geopolymer. The setting time, compressive strength, and degree of reaction were recorded, and the microstructure was examined. The results show that calcium chloride significantly shortens both the initial and final setting times of the geopolymer paste. In addition, sucrose also delays the final setting time significantly. The degrees of reaction of fly ash in the geopolymer paste with the admixtures are all higher than those of the control paste. This contributes to the obvious increases in compressive strength.

  18. Novel selective cannabinoid CB1 receptor antagonist MJ08 with potent in vivo bioactivity and inverse agonistic effects

    Institute of Scientific and Technical Information of China (English)

    Wei CHEN; Cheng XU; Hong-ying LIU; Long LONG; Wei ZHANG; Zhi-bing ZHENG; Yun-de XIE; Li-li WANG; Song LI

    2011-01-01

    To characterize the biological profiles of M J08,a novel selective CB1 receptor antagonist.Methods:Radioligand binding assays were performed using rat brain and spleen membrane preparations.CB1 and CB2 receptor redistribution and intracellular Ca2+ ([Ca2+]1) assays were performed with IN CELL Analyzer.Inverse agonism was studied using intracellular cAMP assays,and in guinea-pig ileum and mouse vas deferens smooth muscle preparations.In vivo pharmacologic profile was assessed in diet-induced obesity (DIO) mice.Results:In radioligand binding assay,M J08 selectively antagonized CB1 receptor (IC50=99.9 nmol/L).In EGFP-CB1_U20S cells,its IC50 value against CB1 receptor activation was 30.23 nmol/L (SR141716A:32.16 nmol/L).WIN 55,212-2 (1 μmol/L) increased [Ca2+]1 in the primary cultured hippocampal neuronal cells and decreased cAMP accumulation in CHO-hCB1 cells.M J08 (10 nmol/L-1O μmol/L)blocked both the WIN 55,212-2-induced effects.Furthermore,M J08 reversed the inhibition of electrically evoked twitches of mouse vas deferens by WIN 55,212-2 (pA2=10.29±1.05).M J08 and SR141716A both showed an inverse agonism activity by markedly promoting the contraction force and frequency of guinea pig ileum muscle.M J08 significantly increased the cAMP level in CHO-hCB1 cells with an EC50 value of 78.6 nmol/L,which was lower than the EC50 value for SR141716A (159.2 nmol/L).Besides the more potent pharmacological effects of cannabinoid CB1 receptor antagonism in DIO mice,such as reducing food intake,decreasing body weight,and ameliorating dyslipidemia,M J08 (10 mg/kg) unexpectedly raised the fasted blood glucose in vivo.Conclusion:M J08 is a novel,potent and selective CB1 receptor antagonist/inverse agonist with potent bioactive responses in vitro and in vivo that may be useful for disclosure the versatile nature of CB1 receptors.

  19. Dietary hyodeoxycholic acid exerts hypolipidemic effects by reducing farnesoid X receptor antagonist bile acids in mouse enterohepatic tissues.

    Science.gov (United States)

    Watanabe, Shiro; Fujita, Kyosuke

    2014-10-01

    Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid-supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1. Hyodeoxycholic acid administration markedly changes the ratio of FXR-antagonist/FXR-agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration. PMID:25189147

  20. Synergistic growth inhibitory effects of the dual endothelin-1 receptor antagonist bosentan on pancreatic stellate and cancer cells.

    Science.gov (United States)

    Fitzner, Brit; Brock, Peter; Holzhüter, Stephanie-Anna; Nizze, Horst; Sparmann, Gisela; Emmrich, Jörg; Liebe, Stefan; Jaster, Robert

    2009-02-01

    Pancreatic stellate cells (PSC) play a key role in pancreatic fibrosis. Activation of PSC occurs in response to pro-fibrogenic stimuli and is maintained by autocrine loops of mediators, such as endothelin (ET)-1. Here, we have evaluated effects of the dual ET receptor antagonist bosentan in models of pancreatic fibrogenesis and cancer. Cell culture studies revealed that PSC and DSL6A pancreatic cancer cells expressed both ET-1 and ET receptors. Bosentan efficiently inhibited proliferation of both cell types and collagen synthesis in PSC. Expression of the myofibroblastic marker alpha-smooth muscle actin, connective tissue growth factor, and ET-1 itself in PSC was reduced, while expression of matrix metalloproteinase-9 was enhanced. Like PSC, DSL6A cells secrete less ET-1 when cultured with bosentan. In a rat model of pancreatic fibrosis, chronic pancreatitis induced by dibutyltin dichloride, a tendency towards a diminished disease progression was observed in a subgroup of rats with less severe disease. Together, our results indicate that bosentan exerts antifibrotic and antitumor effects in vitro. Its efficiency in vivo warrants further investigation. PMID:18612819

  1. Effect of intravenously-administered putative and potential antagonists of ethanol on sleep time in ethanol-narcotized mice

    Energy Technology Data Exchange (ETDEWEB)

    Hatch, R.C.; Jernigan, A.D.

    1988-01-01

    Groups of male CD-1 mice (n = 12/group) were injected intraperitoneally (IP) with 5 g ethanol/kg of body weight. After loss of righting reflex, they were given vehicle or one of 2-3 doses of reputed or potential antagonists of ethanol intravenously (IV). Sleep time was measured from loss to return of righting reflex. Mean sleep time (MST) was increased significantly by a large dose of dl-amphetamine and by 4-aminopyridine. Significant increases were also produced by small and large doses of aminophylline and by yohimbine. MST was not altered significantly by small and medium doses of dl-amphetamine, a medium dose of aminophylline, or by any doses of naloxone, thyrotropin-releasing hormone, propranolol, physostigmine, doxapram, or Ro 15-4513. When Ro 15-4513 was given IP 15 minutes before ethanol (n = 6/group), onset and duration of narcosis were not altered. None of the compounds tested was an effective IV antidote for deep ethanol narcosis because of drug side effects, toxicity, prolongation of MST, or insufficient shortening of MST. 36 references, 1 table.

  2. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist : A Mendelian randomisation analysis

    NARCIS (Netherlands)

    Freitag, Daniel; Butterworth, Adam S.; Willeit, Peter; Howson, Joanna M M; Burgess, Stephen; Kaptoge, Stephen; Young, Robin; Ho, Weang Kee; Wood, Angela M.; Sweeting, Michael; Spackman, Sarah; Staley, James R.; Ramond, Anna; Harshfield, Eric; Nielsen, Sune F.; Grande, Peer; Lange, Leslie A.; Bown, Matthew J.; Jones, Gregory T.; Scott, Robert A.; Bevan, Steve; Porcu, Eleonora; Thorleifsson, Gudmar; Zeng, Lingyao; Kessler, Thorsten; Nikpay, Majid; Do, Ron; Zhang, Weihua; Hopewell, Jemma C.; Kleber, Marcus; Delgado, Graciela E.; Nelson, Christopher P.; Goel, Anuj; Bis, Joshua C.; Dehghan, Abbas; Ligthart, Symen; Smith, Albert V.; Qu, Liming; van 't Hof, Femke N G; de Bakker, Paul I W; Baas, Annette F.; van Rij, Andre; Tromp, Gerard; Kuivaniemi, Helena; Ritchie, Marylyn D.; Verma, Shefali S.; Crawford, Dana C.; Malinowski, Jennifer; de Andrade, Mariza; Kullo, Iftikhar J.; Peissig, Peggy L.; McCarty, Catherine A.; Böttinger, Erwin P.; Gottesman, Omri; Crosslin, David R.; Carrell, David S.; Rasmussen-Torvik, Laura J.; Pacheco, Jennifer A.; Huang, Jie; Timpson, Nicholas J.; Kettunen, Johannes; Ala-Korpela, Mika; Mitchell, Gary F.; Parsa, Afshin; Wilkinson, Ian B.; Gorski, Mathias; Li, Yong; Franceschini, Nora; Keller, Margaux F.; Ganesh, Santhi K.; Langefeld, Carl D.; Bruijn, Lucie; Brown, Matthew A.; Evans, David M.; Baltic, Svetlana; Ferreira, Manuel A.; Baurecht, Hansjörg; Weidinger, Stephan; Franke, Andre; Lubitz, Steven A.; Müller-Nurasyid, Martina; Felix, Janine F.; Smith, Nicholas L.; Sudman, Marc; Thompson, Susan D.; Zeggini, Eleftheria; Panoutsopoulou, Kalliope; Nalls, Mike A.; Singleton, Andrew; Polychronakos, Constantin; Bradfield, Jonathan P.; Hakonarson, Hakon; Easton, Douglas F.; Thompson, Deborah; Tomlinson, Ian P.; Dunlop, Malcolm; Hemminki, Kari; Morgan, Gareth; Eisen, Timothy; Goldschmidt, Hartmut; Allan, James M.; Henrion, Marc; Whiffin, Nicola; Wang, Yufei; Chubb, Daniel; Iles, Mark M.; Bishop, D. Timothy; Law, Matthew H.; Hayward, Nicholas K.; Luo, Yang; Nejentsev, Sergey; Barbalic, Maja; Crossman, David; Sanna, Serena; Soranzo, Nicole; Markus, Hugh S.; Wareham, Nicholas J.; Rader, Daniel J.; Reilly, Muredach; Assimes, Themistocles; Harris, Tamara B.; Hofman, Albert; Franco, Oscar H.; Gudnason, Vilmundur; Tracy, Russell; Psaty, Bruce M.; Farrall, Martin; Watkins, Hugh; Hall, Alistair S.; Samani, Nilesh J.; März, Winfried; Clarke, Robert; Collins, Rory; Kooner, Jaspal S.; Chambers, John C.; Kathiresan, Sekar; McPherson, Ruth; Erdmann, Jeanette; Kastrati, Adnan; Schunkert, Heribert; Stefánsson, Kári; Thorsteinsdottir, Unnur; Walston, Jeremy D.; Tybjærg-Hansen, Anne; Alam, Dewan S.; Al Shafi Majumder, Abdullah; Angelantonio, Emanuele Di; Chowdhury, Rajiv; Nordestgaard, Børge G.; Saleheen, Danish; Thompson, Simon G.; Danesh, John; Houlston, Richard S.

    2015-01-01

    To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods: We created a genetic score combining the effects of alleles of two common

  3. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

    NARCIS (Netherlands)

    C.M. Freitag (Christine); A.S. Butterworth (Adam); J. Willeit (Johann); J.M.M. Howson (Joanna M.M.); S. Burgess (Stephen); S. Kaptoge (Stephen); R. Young (Robin); W.K. Ho (Weang Kee); A.M. Wood (Angela); M. Sweeting (Michael); S. Spackman (Sarah); J.R. Staley (James R.); A. Ramond (Anna); E. Harshfield (Eric); S.F. Nielsen (Sune); P. Grande (Peer); L.A. Lange (Leslie); M.J. Bown (Matthew J.); G.T. Jones (Gregory); R.A. Scott (Robert); S. Bevan (Steve); E. Porcu (Eleonora); G. Thorleifsson (Gudmar); L. Zeng (Lingyao); T. Kessler (Thorsten); M. Nikpay (Majid); R. Do (Ron); W. Zhang (Weihua); J. Hopewell; M.E. Kleber (Marcus); G. Delgado; C.P. Nelson (Christopher P.); A. Goel (Anuj); J.C. Bis (Joshua); A. Dehghan (Abbas); S. Ligthart (Symen); G.D. Smith; L. Qu (Liming); F.N.G. Van 'T Hof (Femke); P.I.W. de Bakker (Paul); A.F. Baas (Annette); A.M. van Rij (Andre); G. Tromp (Gerard); H. Kuivaniemi (Helena); M.D. Ritchie (Marylyn D.); S.S. Verma (Shefali S.); D.C. Crawford (Dana); J. Malinowski (Jennifer); M. de Andrade (Mariza); I. Kullo (Iftikhar); P.L. Peissig (Peggy L.); C.A. McCarty (Catherine A.); E.P. Bottinger (Erwin); R.F. Gottesman (Rebecca); D.R. Crosslin (David); D.S. Carrell (David); L.J. Rasmussen-Torvik (Laura J.); J.A. Pacheco (Jennifer A.); J. Huang (Jie); N. Timpson (Nicholas); J. Kettunen (Johannes); M. Ala-Korpela (Mika); G.F. Mitchell (Gary); A. Parsa (Afshin); I.B. Wilkinson (Ian B.); M. Gorski (Mathias); Y. Li (Yong); N. Franceschini (Nora); M.F. Keller (Margaux); S.K. Ganesh (Santhi); C.D. Langefeld (Carl); L. Bruijn (Lucie); M.A. Brown (Matthew); D.M. Evans (David M.); S. Baltic (Svetlana); M.A. Ferreira (Manuel); H. Baurecht (Hansjörg); S. Weidinger (Stephan); A. Franke (Andre); S.A. Lubitz (Steven); M. Müller-Nurasyid (Martina); J.F. Felix (Janine); N.L. Smith (Nicholas); M. Sudman (Marc); S.D. Thompson (Susan D.); E. Zeggini (Eleftheria); K. Panoutsopoulou (Kalliope); M.A. Nalls (Michael); A. Singleton (Andrew); C. Polychronakos (Constantin); J.P. Bradfield (Jonathan); H. Hakonarson (Hakon); D.F. Easton (Douglas); D. Thompson (Deborah); I.P. Tomlinson (Ian); M. Dunlop (Malcolm); K. Hemminki (Kari); G. Morgan (Gareth); T. Eisen (Timothy); H. Goldschmidt (Hartmut); J.M. Allan (James); M. Henrion (Marc); N. Whiffin (Nicola); Y. Wang (Yufei); D. Chubb (Daniel); M.M. Iles (Mark M.); D.T. Bishop (David Timothy); M.H. Law (Matthew H.); N. Hayward (Nick); Y. Luo (Yang); S. Nejentsev (Sergey); M. Barbalic (maja); D. Crossman (David); S. Sanna (Serena); N. Soranzo (Nicole); H.S. Markus (Hugh); N.J. Wareham (Nick); D.J. Rader (Daniel); M.P. Reilly (Muredach); T.L. Assimes (Themistocles); T.B. Harris (Tamara B.); A. Hofman (Albert); O.H. Franco (Oscar); V. Gudnason (Vilmundur); R.P. Tracy (Russell); B.M. Psaty (Bruce); M. Farrall (Martin); H. Watkins (Hugh); A.S. Hall (Alistair); N.J. Samani (Nilesh); W. März (Winfried); R. Clarke (Robert); F.S. Collins (Francis); J.S. Kooner (Jaspal S.); J.C. Chambers (John C.); S. Kathiresan (Sekar); R. McPherson (Ruth); J. Erdmann (Jeanette); A. Kastrati (Adnan); H. Schunkert (Heribert); J-A. Zwart (John-Anker); U. Thorsteinsdottir (Unnur); J. Walston (Jeremy); A. Tybjaerg-Hansen; D.S. Alam (Dewan S.); A. Al Shafi Majumder (Abdullah); E.D. Angelantonio (Emanuele Di); R. Chowdhury (Rajiv); B.G. Nordestgaard (Børge); D. Saleheen; S.G. Thompson (Simon); J. Danesh (John); R. Houlston (Richard)

    2015-01-01

    textabstractTo investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods: We created a genetic score combining the effects of alleles of

  4. Effect of the Cannabinoid Receptor-1 antagonist SR141716A on human adipocyte inflammatory profile and differentiation

    Directory of Open Access Journals (Sweden)

    Murumalla Ravi

    2011-11-01

    Full Text Available Abstract Background Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. SR141716A, a cannabinoid receptor 1 (CB1 antagonist, shows significant improvement in clinical status of obese/diabetic patients. Therefore, we studied the effect of SR141716A on human adipocyte inflammatory profile and differentiation. Methods Adipocytes were obtained from liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. Media and cells were collected for secretory (ELISA and expression analysis (qPCR. Triglyceride accumulation was observed using oil red-O staining. Cholesterol was assayed by a fluorometric method. 2-AG and anandamide were quantified using isotope dilution LC-MS. TLR-binding experiments have been conducted in HEK-Blue cells. Results In LPS-treated mature adipocytes, SR141716A was able to decrease the expression and secretion of TNF-a. This molecule has the same effect in LPS-induced IL-6 secretion, while IL-6 expression is not changed. Concerning MCP-1, the basal level is down-regulated by SR141716A, but not the LPS-induced level. This effect is not caused by a binding of the molecule to TLR4 (LPS receptor. Moreover, SR141716A restored adiponectin secretion to normal levels after LPS treatment. Lastly, no effect of SR141716A was detected on human pre-adipocyte differentiation, although the compound enhanced adiponectin gene expression, but not secretion, in differentiated pre-adipocytes. Conclusion We show for the first time that some clinical effects of SR141716A are probably directly related to its anti-inflammatory effect on mature adipocytes. This fact reinforces that adipose tissue is an important target in the development of tools to treat the metabolic syndrome.

  5. Calcium Electroporation: Evidence for Differential Effects in Normal and Malignant Cell Lines, Evaluated in a 3D Spheroid Model.

    Directory of Open Access Journals (Sweden)

    Stine Krog Frandsen

    Full Text Available Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill efficacy-and normal cell sensitivity.Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29, a bladder transitional cell carcinoma (SW780, and a breast adenocarcinoma (MDA-MB231, as well as on primary normal human dermal fibroblasts (HDF-n.The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p<0.0001 or electrochemotherapy using bleomycin (p<0.0001. Strikingly, the size of normal fibroblast spheroids was neither affected after calcium electroporation nor electrochemotherapy using bleomycin, indicating that calcium electroporation, like electrochemotherapy, will have limited adverse effects on the surrounding normal tissue when treating with calcium electroporation. The intracellular ATP level, which has previously been shown to be depleted after calcium electroporation, was measured in the spheroids after treatment. The results showed a dramatic decrease in the intracellular ATP level (p<0.01 in all four spheroid types-malignant as well as normal.In conclusion, calcium electroporation seems to be more effective in inducing cell death in cancer cell spheroids than in a normal fibroblast spheroid, even though intracellular ATP level is depleted in all spheroid types after treatment. These results may indicate an important therapeutic window for this therapy; although further studies are needed in vivo and in patients to investigate the effect of calcium electroporation on surrounding normal tissue when

  6. Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation

    Science.gov (United States)

    Chua, Yansong; Morrison, Abigail

    2016-01-01

    The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be

  7. Regional Fos-expression induced by γ-hydroxybutyrate (GHB): comparison with γ-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.

    Science.gov (United States)

    van Nieuwenhuijzen, P S; McGregor, I S; Chebib, M; Hunt, G E

    2014-09-26

    γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor γ-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors.

  8. The Effect of Corticosteroids on Urinary Calcium Excretion. A Pilot Study

    Directory of Open Access Journals (Sweden)

    Semra Soylu Gungor

    2014-12-01

    Full Text Available Aim: Corticosteroids are the main drugs in the treatment of nephrotic syndrome and bronchial hyperreactivity and can be used for long periods in high doses. From clinical use and experiments, systemic corticosteroids are known to cause hypercalciuria. In this study we aim to determine the effect of corticosteroids on urinary calcium excretion and to assess related parameters in children with chronic disease. Material and Method: Thirty-nine children with nephrotic syndrome and bronchial hyperreactivity from ages 1-15 and 15 same-aged healthy controls of the same sex are included in the study. Nineteen patients with nephrotic syndrome using 2 mg/kg/day oral prednisolone are included in group 1, and 20 patients with bronchial hyperreactivity who use inhaled 2x200 µgr budesonide are included in group 2. All children%u2019s bone formation (serum osteocalcin and alkaline phosphatase, resorption (urine deoxypyridinoline crosslinks/creatinine, and metabolism markers (parathyroid hormone, calcium, and phosphate were analyzed. Results: Post-treatment urinary calcium/creatinine ratio was increased in the nephrotic syndrome group. Osteocalcine levels were found decreased in nephrotic syndrome patients who take oral prednisolone treatment. Urine deoxypyridinoline crosslinks/creatinine ratio levels were found low in both nephrotic syndrome and bronchial hyperreactivity patients, contrary to expectations.Discussion: In this study we found that oral prednisolone usage increased renal calcium excretion while inhaled budesonide did not increase renal calcium excretion. We believe that oral prednisolone repressed the bone formation. To further investigate low urine deoxypyridinoline crosslinks/creatinine ratio, more prospective studies with a greater number of participants are required.

  9. Effect of TGFβ on calcium signaling in megakaryocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jing [Department of Physiology I, University of Tübingen, Tübingen (Germany); Schmid, Evi [Department of Physiology I, University of Tübingen, Tübingen (Germany); Department of Pediatric Surgery and Pediatric Urology, University Children' s Hospital Tübingen, Tübingen (Germany); Almilaji, Ahmad; Shumilina, Ekaterina [Department of Physiology I, University of Tübingen, Tübingen (Germany); Borst, Oliver [Department of Physiology I, University of Tübingen, Tübingen (Germany); Department of Cardiology & Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Laufer, Stefan [Department of Pharmacy, University of Tübingen, Tübingen (Germany); Gawaz, Meinrad [Department of Cardiology & Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology I, University of Tübingen, Tübingen (Germany)

    2015-05-22

    TGFβ is a powerful regulator of megakaryocyte maturation and platelet formation. As previously shown for other cell types, TGFβ may up-regulate the expression of the serum & glucocorticoid inducible kinase SGK1, an effect requiring p38 kinase. SGK1 has in turn recently been shown to participate in the regulation of cytosolic Ca{sup 2+} activity ([Ca{sup 2+}]{sub i}) in megakaryocytes and platelets. SGK1 phosphorylates the IκB kinase (IKKα/β), which in turn phosphorylates the inhibitor protein IκBα resulting in nuclear translocation of nuclear factor NFκB. Genes up-regulated by NFκB include Orai1, the pore forming ion channel subunit accomplishing store operated Ca{sup 2+} entry (SOCE). The present study explored whether TGFβ influences Ca{sup 2+} signaling in megakaryocytes. [Ca{sup 2+}]{sub i} was determined by Fura-2 fluorescence and SOCE from the increase of [Ca{sup 2+}]{sub i} following re-addition of extracellular Ca{sup 2+} after store depletion by removal of extracellular Ca{sup 2+} and inhibition of the sarcoendoplasmatic Ca{sup 2+} ATPase (SERCA) with thapsigargin (1 μM). As a result, TGFβ (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38 kinase inhibitor Skepinone-L (1 μM), SGK1 inhibitor EMD638683 (50 μM) and NFκB inhibitor wogonin (100 μM). In conclusion, TGFβ is a powerful regulator of store operated Ca{sup 2+} entry into megakaryocytes, an effect mediated by a signaling cascade involving p38 kinase, SGK1 and NFκB. - Highlights: • TGFβ up-regulates store operated Ca{sup 2+} entry (SOCE) in megakaryocytes. • The effect of TGFβ on SOCE is blunted by p38 kinase inhibitor Skepinone-L. • The effect of TGFβ on SOCE is virtually abrogated by SGK1 inhibitor EMD638683. • The effect of TGFβ on SOCE is almost abolished by NFκB inhibitor wogonin. • The effect of TGFβ is expected to enhance sensitivity of platelets to activation.

  10. Effects of the methyltrimethoxysilane coupling agent on phenolic and miscanthus composites containing calcium sulfite scrubber material

    Science.gov (United States)

    Jones, Sean

    The purpose of this research is to test the effects of methyltrimethoxysilane coupling agent on composite material containing calcium sulfite obtained from the Southern Illinois Power Co-operative. This scrubber material and the miscanthus plant are of interest due to their use in coal burning power plants to reduce toxic emission. When calcium sulfate is passed through coal fire gas emissions it absorbs mercury and sulfur. In these composites it is used as filler to reduce cost. Miscanthus is a source of both cellulose reinforcement and some natural resin. This plant has low care requirements, little mineral content, useful energy return, and positive environmental effects. Under investigation is whether a post-cure procedure or a silane coupling agent will positively impact the composite. Hot pressing alone may not be enough to fully cure the phenolic. It is hoped that the silane will increase the strength characteristics of the composite by enhancing adhesion between the calcium sulfite and phenolic resin. Possible effects on the miscanthus by the silane will also be tested. Phenolic is being utilized because of its recycling and biodegradable properties along with cost effectiveness in mass production. Composite mechanical performance was measured through 3-point bending to measure flexural strength and strain at breakage. A dynamic mechanical analyzer (DMA) was used to find thermomechanical properties. The post-cure was found to be effective, particularly on the final composite containing silane. When methyltrimethoxysilane was added to the miscanthus prior to fabrication, it was found to reduce flexural strength and density. However the addition of methyltrimethoxysilane to the calcium sulfite altered thermo-mechanical properties to a state more like pure phenolic, with added flexibility and thermal stability.

  11. Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    WANG Li-chun; ZENG Wu-tao; LIU Jun; DONG Yu-gang; TANG An-li; FENG Chong; MA Hong; HE Jian-gui; LIAO Xin-xue; CHEN Wen-fang; LENG Xiu-yu; MA Li; MAI Wei-yi; TAO Jun

    2005-01-01

    Background Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Results The fraction of cell shortening (FS%) and [Ca2+]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51±1.15 vs 13.21±1.49;[Ca2+]imax:330.85±50.05 vs 498.16±14.07; both P<0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/β-Actin: 0.51±0.12 vs 0.19±0.06, P<0.01; RPLB/β-Actin: 0.26±0.12 vs 0.20±0.08, P<0.05), while SERCA2 mRNA was downregulated (0.48±0.10 vs 0.80±0.11, P<0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P<0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141±0.047 and 1.074±0.081 times of that in PS group respectively (both P<0.05), and SERCA2 protein levels were 0.803±0.100 and 0.893±0.084 times of that in PS group respectively (both P<0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P<0.05).Conclusion ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

  12. Effects of angiotensin Ⅱ receptor antagonist, Losartan on the apoptosis, proliferation and migration of the human pancreatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Wen-Bin Liu; Xing-Peng Wang; Kai Wu; Ru-Ling Zhang

    2005-01-01

    AIM: To investigate the effects of AT1 (Type 1 angiotensin Ⅱ receptor) antagonist (Losartan) on the apoptosis,proliferation and migration of the human pancreaticstellate cells (hPSCs).METHODS: hPSCs were isolated from pancreatic sample of patients with pancreatic carcinoma using radioimmunoassay (RIA) technique to detect the concentration of AngⅡ in culture media and cell homogenate. Immunocytochemistry (ICC) and in situ hybridization (ISH) methods were utilized to test AT1 expression in hPSCs. Effects of Losartan on hPSCs proliferation, apoptosis and migration were investigated using BrdU incorporation, TUNEL, flow cytometry (FCM),and phase-contrast microscope separately when cells treated with Losartan. Immunofluorescence and Western blot were applied to quantify the expression of type Ⅰ collagen in hPSCs.RESULTS: There exists AT1 expression in hPSCs, while no AngⅡ was detected in culture media and cell homogenate. Losartan induces cell apoptosis in a doseand time-dependent manner (apparently at 10-5 mol/L),no pro-proliferative effect was observed in the same condition.Corresponding dosage of Losartan can also alleviate the motion capability and type Ⅰ collagen content of hPSCs compared with AngⅡ treatment and non-treatment control groups.CONCLUSION: These findings suggest that paracrine not autocrine functions of AngⅡ may have effects on hPSCs,which was mediated by AT1 expressed on cells, while Losartan may exert anti-fibrotic effects by inhibiting hPSCs motion and partly by inducing apoptosis.

  13. Effects of a 5-HT3 agonist and antagonist on inter-male aggression in Mus musculus

    Directory of Open Access Journals (Sweden)

    Michael Kerchner

    2006-01-01

    Full Text Available Research has revealed an inverse relationship between serotonin (5-HT levels in the brain and aggressive behavior. However, effects on aggression at the level of the receptor have yet to be elucidated for many 5-HT receptor subtypes. This study examined the effects of the 5-HT3 receptor agonist m-chlorophenylbiguanide (mCPBG and antagonist ondansetron on inter-male aggression in mice. Using a resident-intruder paradigm designed to assess both offensive and defensive aggression, male C57BL/6J mice received 1 mg/kg i.p. injections of either mCPBG, ondansetron, or an inactive vehicle and were subsequently exposed to male AKR/J mice for a period of 10 minutes. Attack latency and the proportion of time engaged in a range of defensive behaviors were recorded. Subject C57BL/6J mice were then immediately run in an open field test for an additional 10 minutes to examine any anxiolytic or sedative effects of the drugs. Results show no significant differences between drug groups in either offensive or defensive behavior. No significant differences were observed between drug groups and open field activity; however, significant differences were seen between the offensive and defensive condition in the open field. In conclusion, this study fails to reveal any significant effects of the 5-HT3 agents on inter-male aggression, which may reflect a functional difference between the 5-HT3 receptor and the remaining G-protein coupled 5-HT receptor. However, this conclusion is limited by the large variance in behavior combined with small sample sizes, or the possibility of a drug dose insufficient for behavioral effects.

  14. Cardiovascular effects of calcium-channel blocker with radionuclide ventriculography

    International Nuclear Information System (INIS)

    Hemodynamic parameters were assessed before and 0.5h after the p.o. of 20 mg of nifedipine (NIF) in 31 patients and 60 mg of dilitiazem (DIL) in 24 patients with radionuclide ventriculography. After oraltherapy, NIF improved the LV pumping function, LVEF increased from 0.56 to 0.63 (P 2 (P 2), respectively, P 2, respectively, P > 0.05. In the group of patients with old myocardial infarction, both negative effect were observed

  15. In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder.

    Science.gov (United States)

    Barth, V; Need, A B; Tzavara, E T; Giros, B; Overshiner, C; Gleason, S D; Wade, M; Johansson, A M; Perry, K; Nomikos, G G; Witkin, J M

    2013-02-01

    Dopamine D(3) receptors have eluded definitive linkage to neurologic and psychiatric disorders since their cloning over 20 years ago. We report a new method that does not employ a radiolabel for simultaneously defining in vivo receptor occupancy of D(3) and D(2) receptors in rat brain after systemic dosing using the tracer epidepride (N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide). Decreases in epidepride binding in lobule 9 of cerebellum (rich in D(3) receptors) were compared with nonspecific binding in the lateral cerebellum. The in vivo occupancy of the dopamine D(3) receptors was dose dependently increased by SB-277011A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and U99194 (2,3-dihydro-5,6-dimethoxy- N,N-dipropyl-1H-inden-2-amine). Both antagonists increased extracellular levels of acetylcholine (ACh) in the medial prefrontal cortex of rats and modified brain-tissue levels of ACh and choline. Consistent with these findings, the D(3) receptor antagonists enhanced the acquisition of learning of rats either alone or in the presence of the norepinephrine uptake blocker reboxetine as with the attention-deficit-hyperactivity disorder (ADHD) drug methylphenidate. Like reboxetine, the D(3) receptor antagonists also prevented deficits induced by scopolamine in object recognition memory of rats. Mice in which the dopamine transporter (DAT) has been deleted exhibit hyperactivity that is normalized by compounds that are effective in the treatment of ADHD. Both D(3) receptor antagonists decreased the hyperactivity of DAT(-/-) mice without affecting the activity of wild type controls. The present findings indicate that dopamine D(3) receptor antagonists engender cognition-enhancing and hyperactivity-dampening effects. Thus, D(3) receptor blockade could be considered as a novel treatment approach for cognitive deficits and hyperactivity syndromes, including those observed in ADHD. PMID:23197772

  16. Effects on anionic salts in a pre-partum dairy ration on calcium metabolism

    OpenAIRE

    C.J. Van Dijk; D.C. Lourens

    2001-01-01

    The effects of anionic salts in the transition diet on serum and urine calcium at calving and on peripartal health, subsequent milk production and fertility performance were studied in a well-managed, high-producing Friesland dairy herd. Over a period of a year, approximately 21 days before the expected date of calving, 28 pre-partum heifers and 44 multiparous dry cows were randomly allocated within parity to 1 of 2 transition diets, designated control and experimental anionic diets. The anio...

  17. Mechanisms underlying the effects of inulin-type fructans on the intestinal calcium absorption

    OpenAIRE

    Raschka, Ladislav

    2005-01-01

    Inulin-type fructans in a diet are selectively fermented by the large intestinal microflora which causes a multitude of effects that are considered as beneficial for human health and well-being. One of these well documented actions is an increased intestinal calcium absorption, similarly observed in experimental animals and in humans. Since the underlying mechanisms are not yet understood, various in vivo and in vitro experiments with rats were conducted to elucidate the molecular actions of ...

  18. Antagonistic effect of disulfide-rich peptide aptamers selected by cDNA display on interleukin-6-dependent cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Naoto, E-mail: nemoto@fms.saitama-u.ac.jp [Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Innovation Center for Startups, National Institute of Advanced Industrial Science and Technology, 2-2-2 Marunouchi, Chiyoda-ku, Tokyo 100-0005 (Japan); Janusys Corporation, 508, Saitama Industrial Technology Center, Skip City, 3-12-18 Kami-Aoki, Kawaguchi, Saitama 333-0844 (Japan); Tsutsui, Chihiro [Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yamaguchi, Junichi [Innovation Center for Startups, National Institute of Advanced Industrial Science and Technology, 2-2-2 Marunouchi, Chiyoda-ku, Tokyo 100-0005 (Japan); Applied Gene Technology, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 (Japan); Ueno, Shingo [Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Machida, Masayuki [Applied Gene Technology, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 (Japan); Kobayashi, Toshikatsu [Innovation Center for Startups, National Institute of Advanced Industrial Science and Technology, 2-2-2 Marunouchi, Chiyoda-ku, Tokyo 100-0005 (Japan); Janusys Corporation, 508, Saitama Industrial Technology Center, Skip City, 3-12-18 Kami-Aoki, Kawaguchi, Saitama 333-0844 (Japan); Sakai, Takafumi [Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan)

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. Black-Right-Pointing-Pointer Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. Black-Right-Pointing-Pointer Inhibitory effect of peptide depends on number and pattern of its disulfide bonds. -- Abstract: Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library by in vitro peptide selection using the evolutionary molecular engineering method 'cDNA display'. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.

  19. Synergistic and antagonistic effects on fatty acid composition in the liver mitochondria of rats by thyroidectomy and streptozotocin-administration.

    Science.gov (United States)

    Nishida, M; Sasaki, T; Terada, H; Kawada, J

    1991-12-01

    The content of individual fatty acid component in mitochondria of livers from thyroidectomized (Tx) and streptozotocin (STZ)-induced diabetic rats was measured to investigate how different hormones are interrelated to control the amount of a particular fatty acid in mitochondria. The results showed (1) diabetes, in general, affected fatty acid contents more severely than hypothyroidism, regardless of the direction of the changes; (2) Hypothyroidism and diabetes affected antagonistically the contents of C16 species and C18:1, which belong to a de novo synthesis (oleate series). However, the two pathological conditions affected synergistically those of higher unsaturated species, eg. C18:2, C20:3 and C20:4, which belong to a dietary-dependent synthesis (linoleate series). These results strongly indicated that each desaturation site and elongation site is affected in a preferential order by either thyroid hormone or insulin, and that hypothyroidism and diabetes have their effects differently on the process of de novo synthesis and the pathways initiated from an essential fatty acid in mitochondria. PMID:1837932

  20. Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

    2016-09-01

    Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia. PMID:26674759

  1. Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements.

    Science.gov (United States)

    Grundemar, L; Ekelund, M

    1996-11-01

    The aim was to examine effects of a newly developed neuropeptide Y (NPY)-receptor antagonist, BIBP3226 and to characterize NPY-receptors in the isolated guinea pig caval vein and human subcutaneous artery, respectively. BIBP3226 shift of the concentration-response curve to the Y1-receptor selective agonist [Pro34]NPY in the guinea pig caval vein. Regression analysis of the Schild plot gave a pA2-value of 7.58 (7.20-8.33, 95% confidence interval), slope of regression line 0.96 (0.52-1.39, 95% confidence interval) and a correlation coefficient of 0.78. NPY and the C-terminal NPY 2-36 evoked equipotent concentration-dependent contractions, both of which were sensitive to BIBP3226. Although less potent than NPY 2-36, also the contraction induced by NPY 5-36 was antagonized by BIBP3226. In the human subcutaneous artery [Pro34]NPY but not NPY 2-36 (shift of the concentration-response curve to [Pro34]NPY (from 7.38 +/- 0.10 to 6.95 +/- 0.16 (P demand on the N-terminal part of NPY than that of human Y1-receptors. PMID:8936561

  2. Effect of GNTI,a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice

    Institute of Scientific and Technical Information of China (English)

    Chun-ting QI; Hong ZOU; Chen-hao ZHANG; Qing-lian XIE; Mei-lei JIN; Lei YU

    2006-01-01

    Aim:To examine the effect of GNTI[5'-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,-5α-epoxy-3-14-dihydroxy-6,7-2',3'-indolomorphinan],a selective antagonist for the kappa opioid receptor,in the MK-801 (dizocilpine maleate)-induced behavioral model of psychosis in schizophrenia as a way to explore the involvement of the kappa opioid receptor in modulating psychotic symptoms of schizophrenia.Methods:Two doses 0f MK-801 (0.3 mg/kg and 0.6 mg/kg) were administered by systemic injection in mice to induce psychosis-like behavior as a rodent schizophrenia model, preceded by an injection of different doses of GNTI. Both locomotion and stereotypy were measured as the behavioral endpoints for quantitative analysis.Results:GNTI inhibited MK-801-induced hyperlocomotion and stereotypy.In particular,GNTI showed differential modulation of stereotypy induced by 0.3 mg/kg VS 0.6 mg/kg MK-801.Conclusion:Antagonism of kappa opioid receptors attenuates MK-801-induced behavior,suggesting a potential involvement of the kappa opioid receptor in psychosis-like symptoms of schizophrenia.GNTI aDpears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo.

  3. Effects of microbial phytase on apparent and standardized total tract digestibility of calcium in calcium supplements fed to growing pigs.

    Science.gov (United States)

    González-Vega, J C; Walk, C L; Stein, H H

    2015-05-01

    An experiment was conducted to test the hypothesis that differences in the apparent total tract digestibility (ATTD) and standardized total tract digestibility (STTD) of Ca exist among Ca supplements and that inclusion of microbial phytase increases the ATTD and STTD of Ca. One hundred and four growing barrows (average initial BW of 17.73 ± 2.53 kg) were allotted to a randomized complete block design with 13 dietary treatments and 8 pigs per treatment. A basal diet containing corn, cornstarch, potato protein isolate, soybean oil, calcium carbonate, monosodium phosphate, vitamins, and minerals was formulated. Five additional diets were formulated by adding monocalcium phosphate (MCP), dicalcium phosphate (DCP), calcium carbonate, Lithothamnium calcareum Ca, or a high-Ca sugar beet co-product to the basal diet at the expense of cornstarch. Six additional diets that were similar to the previous 6 diets with the exception that they also contained 500 units per kilogram of microbial phytase were also formulated. A Ca-free diet was used to determine basal endogenous losses of Ca. Feces were collected using the marker-to-marker approach. Results indicated that regardless of inclusion of microbial phytase, MCP had the greatest (P DCP were greater (P DCP diets than in pigs fed calcium carbonate, L. calcareum Ca, or the sugar beet co-product, but pigs fed calcium carbonate diets had greater ( PDCP. Basal, MCP, and DCP diets had greater ATTD of P than the other diets, and inclusion of microbial phytase increased the ATTD and STTD of Ca and the ATTD of P in the diets.

  4. Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Alessandro Gozzi

    Full Text Available Orexins are neuro-modulatory peptides involved in the control of diverse physiological functions through interaction with two receptors, orexin-1 (OX1R and orexin-2 (OX2R. Recent evidence in pre-clinical models points toward a putative dichotomic role of the two receptors, with OX2R predominantly involved in the regulation of the sleep/wake cycle and arousal, and the OX1R being more specifically involved in reward processing and motivated behaviour. However, the specific neural substrates underlying these distinct processes in the rat brain remain to be elucidated. Here we used functional magnetic resonance imaging (fMRI in the rat to map the modulatory effect of selective OXR blockade on the functional response produced by D-amphetamine, a psychostimulant and arousing drug that stimulates orexigenic activity. OXR blockade was produced by GSK1059865 and JNJ1037049, two novel OX1R and OX2R antagonists with unprecedented selectivity at the counter receptor type. Both drugs inhibited the functional response to D-amphetamine albeit with distinct neuroanatomical patterns: GSK1059865 focally modulated functional responses in striatal terminals, whereas JNJ1037049 induced a widespread pattern of attenuation characterised by a prominent cortical involvement. At the same doses tested in the fMRI study, JNJ1037049 exhibited robust hypnotic properties, while GSK1059865 failed to display significant sleep-promoting effects, but significantly reduced drug-seeking behaviour in cocaine-induced conditioned place preference. Collectively, these findings highlight an essential contribution of the OX2R in modulating cortical activity and arousal, an effect that is consistent with the robust hypnotic effect exhibited by JNJ1037049. The subcortical and striatal pattern observed with GSK1059865 represent a possible neurofunctional correlate for the modulatory role of OX1R in controlling reward-processing and goal-oriented behaviours in the rat.

  5. Effects and mechanism of different adrenergic receptor antagonists on left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats

    Institute of Scientific and Technical Information of China (English)

    HU Qin; LI Long-gui; ZHANG Yun

    2004-01-01

    To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the ef-fects of three kinds of adrenergic receptor blockers: Carvedilol (CAR), Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypearophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA) was used in this study. Thirty two male istar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER.emodynamics, ventric-ular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ /Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ/Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ/Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was indepen-dent of beta-adrenergic receptor antagonist.

  6. Antagonistic effects of aldosterone on corticosterone-mediated changes in exploratory behavior of adrenalectomized rats

    NARCIS (Netherlands)

    Veldhuis, H D; De Kloet, E R

    1983-01-01

    The effect of aldosterone administration on exploratory activity of chronic adrenalectomized (10 days) male rats was investigated. Aldosterone (30 micrograms/100 g body wt sc) administered 1 hr or 30 min prior to the behavioral test failed to normalize disturbed exploratory activity of adrenalectomi

  7. Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

    NARCIS (Netherlands)

    Morens, C; Norregaard, P; Receveur, JM; van Dijk, G; Scheurink, AJW; Nørregaard, Pia; Receveur, Jean-Marie

    2005-01-01

    Melanin concentrating hormone (MCH) is a regulator of ingestive behavior, but several issues regarding its effects on specific components of ingestive behavior remain to be elucidated. Therefore, we injected, in the 3rd ventricle of male Wistar rats, saline, MCH (5 mu g), MCH (5 mu g) together with

  8. Effects of a 5-HT3 antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

    OpenAIRE

    Marciani, Luca; Wright, Jeff; Foley, Stephen; Hoad, Caroline L.; Totman, John J; Bush, Debbie; Hartley, Caroline; Armstrong, Alexander; Manby, Paul; Blackshaw, Elaine; Perkins, Alan C; Gowland, Penny A.; Spiller, Robin

    2010-01-01

    Abstract Background 5-HT3 antagonists have been shown to be effective in relieving symptoms of IBS-D. Using a recently validated MRI method we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility. Aim To assess the effects of ondansetron compared with placebo in healthy volunteers o...

  9. Effects due to rhizospheric soil application of an antagonistic bacterial endophyte on native bacterial community and its survival in soil: A case study with Pseudomonas aeruginosa from banana

    OpenAIRE

    Pious eThomas; Aparna Chandra Sekhar

    2016-01-01

    Effective translation of research findings from laboratory to agricultural fields is essential for the success of biocontrol or growth promotion trials employing beneficial microorganisms. The rhizosphere is to be viewed holistically as a dynamic ecological niche comprising of diverse microorganisms including competitors and noxious antagonists to the bio-inoculant. This study was undertaken to assess the effects due to the soil application of an endophytic bacterium with multiple pathogen an...

  10. Effects of 5-HT uptake inhibitors, agonists and antagonists on the burying of harmless objects by mice; a putative test for anxiolytic agents.

    OpenAIRE

    Njung'e, K.; Handley, S. L.

    1991-01-01

    1. The effects of 5-hydroxytryptamine (5-HT) uptake inhibitors, agonists and antagonists have been evaluated on mouse marble-burying behaviour, a putative test for anxiolytic agents. The high levels of locomotor activity occurring on first exposure to a circular runway (runway were used as a separate test of non-specific drug effects. 2. Fluvoxamine, zimeldine, indalpine and citalopram dose-dependently inhibited burying without affecting runway activity. 5-Hydroxytryptophan (5-HTP, with carbi...

  11. Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

    OpenAIRE

    Sharma, Pawana; Scotland, Graham; Cruickshank, Moira; Tassie, Emma; Fraser, Cynthia; Burton, Christopher; Croal, Bernard; Ramsay, Craig R.; Brazzelli, Miriam

    2015-01-01

    Objectives To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. Design Systematic review of current evidence and economic modelling. Data sources Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. Study eligibil...

  12. Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5-HT.

    OpenAIRE

    Gartside, S E; Umbers, V; Hajós, M.; Sharp, T.

    1995-01-01

    1. The acute inhibitory effect of selective 5-hydroxytryptamine (serotonin) reuptake inhibitors (SSRIs) on 5-HT neuronal activity may offset their ability to increase synaptic 5-HT in the forebrain. 2. Here, we determined the effects of the SSRI, paroxetine, and a novel selective 5-HT1A receptor antagonist, WAY 100635, on 5-HT cell firing in the dorsal raphé nucleus (DRN), and on extracellular 5-HT in both the DRN and the frontal cortex (FCx). Extracellular electrophysiological recording and ...

  13. Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent.

    Science.gov (United States)

    Danhof, I E

    1982-01-01

    Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

  14. Effects of Different Concentrations and Applications of Calcium on Storage Life and Physicochemical Characteristics of Papaya (Carica Papaya L.

    Directory of Open Access Journals (Sweden)

    T. M. M. Mahmud

    2008-01-01

    Full Text Available Papaya (Carica Papaya L. fruits index 2 were treated with 1.5, 2.5 and 3.5% solutions of calcium chloride by dipping and vacuum infiltration (-33 Kpa or untreated (0% as control. Effects of these treatments were evaluated on storage life and postharvest quality characteristics of papaya. After 21 days of storage at 13±1°C, the fruits were removed from storage for physicochemical analysis. Following additional five days holding in the storage condition for fruits used for evaluation of the rate of disease incidence and storage life. Postharvest dip treatments at different concentrations of calcium prolonged storage life, slowed down the ripening processes and maintained the quality of papaya. Whereas, it was effectively greater with calcium infiltration treatments than that for dip treatments. Calcium infiltration extended the storage life and retained the quality as calcium concentrations increased up to 2.5% and then declined. The desired effect was obtained at 2.5% infiltration compared with other treatments. The least disease incidence was found in those fruits infiltrated with 2.5% calcium. Hence, it can be concluded that postharvest infiltration of calcium at 2.5% has the potential to control disease incidence, prolong the storage life and preserve valuable attributes of postharvest papaya, presumably because of its effects on inhibition of ripening and senescence process and loss of the fruit firmness of papaya.

  15. The Effect of Calcium Hydroxide on the Bond Strength of Resilon/Epiphany Self-Etch and Assessment of Calcium Hydroxide Removal Techniques: An Ex-Vivo Study

    Directory of Open Access Journals (Sweden)

    B. Bolhari

    2012-01-01

    Full Text Available Objective: Calcium hydroxide is the most widely used intracanal medicament in endodontics, which should be removed prior to permanent root canal filling to minimize its intervention with the bonding of endodontic sealers. This ex-vivo study aimed to evaluate the effect of pretreatment with calcium hydroxide on the bond strength of Resilon/Epiphany self etch (SE to the radicular dentin after removing the calcium hydroxide by hand file or ultrasonic methods.Materials and Methods: Thirty-six single-rooted human extracted teeth were used in this study. After root canal preparation, the teeth were divided into three groups. In group 1, as the control, no pretreatment was performed; while in groups 2 and 3, this was carried out using calcium hydroxide paste. After one week, the paste was removed with hand stainless steel K-files in group 2 and ultrasonic instrumentation in group 3. All samples were obturated with Resilon/Epiphany SE. One-millimeter slices of mid-root dentin were prepared for the push-out test (14 slices per group. After the bond strength was assessed, the failure modes were examined. The data were analyzed using one-way ANOVA and Dunnett Post Hoc tests.Results: Group 2 significantly showed the lowest bond strength (0.947 ± 0.47 (P = 0.01. No significant differences were found between the control group (2.32 ± 1.43 and group 3 (1.78 ± 1.04 (P = 0.01.Conclusions: Under the conditions of this ex vivo study, calcium hydroxide as the intracanal medicament and its removal using hand instrumentation adversely affected the bond strength of Resilon/Epiphany SE.

  16. Differential effects of organic compounds on cucumber damping-off and biocontrol activity of antagonistic bacteria

    DEFF Research Database (Denmark)

    Li, Bin; Ravnskov, Sabine; Guanlin, X.;

    2011-01-01

    The influence of the organic compounds tryptic soy broth, cellulose, glucose and chitosan on cucumber damping-off caused by Pythium aphanidermatum and biocontrol efficacy of the biocontrol agents (BCAs) Paenibacillus macerans and P. polymyxa were examined in a seedling emergence bioassay. Results...... showed that the organic compounds differentially affected both pathogen and BCAs. Tryptic soy broth, glucose and chitosan increased Pythium damping-off of cucumber, compared to the control treatment without organic compounds, whereas cellulose had no effect. Both Paenibacillus species had biocontrol...... effects against Pythium damping-off compared with the corresponding treatments with P. aphanidermatum alone, but the biocontrol efficacy depended on the type of organic compounds added. Both BCAs counteracted damping-off in treatments with TSB and chitosan. However, P. polymyxa counteracted damping...

  17. Therapeutic effect of ifenprodil,a NMDA receptor antagonist,on drug dependence

    Institute of Scientific and Technical Information of China (English)

    SuzukT; NaritM

    2002-01-01

    Although drug dependence has been treated by the adonist-therapy,the specific drug therapy for drug dependence has not been established.Ifenprodil is consibdred to specifically block the NMDA receptor consisted of NR1/NR2B subunits without undesirable adverse reactions,such as psychotomimetic action and psychological dependence,while ketamine and MK-801 can block both NMDA receptors consisted of NR1/NR2A and NR1/NR2B subunits with the undesirable adverse reactions.In the present study,we designed to examine the effect of ifenprodil on drug dependence in rodents.Pretreatment with ifenprodil suppressed the expression of withdrawal signs in morphine-, diazepam-and alcohol-dependent rats and mics.Rewarding effects of morphine,methamphetamine and cocaine as well as physical dependence,were suppressed by pretreatment with ifenprodil in rats and mice.These results suggest that ifenprodil be useful in treating drug dependence.

  18. Effects of the uncompetitive NMDA receptor antagonist memantine on spatial memory in medial septal lesioned rats.

    Science.gov (United States)

    Dashniani, M; Burjanadze, M; Beselia, G; Chkhikvishvili, N; Kruashvili, L

    2011-12-01

    These experiments examined the effects of acute administration of memantine (2.5 or 5 mg/kg) or saline on spatial memory and learning process within single sessions, on place versions of food-rewarded maze in MS electrolytic lesioned and sham-lesioned rats. Sham-lesioned rats trained in the place task learned more rapidly than did MS electrolytic lesioned rats. This fact certifies for obvious deficit of the place learning performance strategy in the MS-lesioned rats. The results indicate that the drug-treated (5 mg/kg memantine) sham-lesioned rats exhibited significantly impaired performance relative to the saline controls in terms of trials-to-criterion (Pimprove performance in place learning task in MS electrolytic lesioned rats. Our experimental data support the interpretation that memantine does not produce intolerable side effects in human AD patients because it is being used at doses that are below the threshold for interacting with NMDA receptors.

  19. The effect of supplementary calcium on blood pressure in healthy adult women aged 18-30 years in Tehran, Iran

    Science.gov (United States)

    Entezari, Mohammad Hassan

    2015-01-01

    Introduction: Cardiovascular disease is the major cause of mortality in developed countries and has an increasing trend in developing countries. There are some evidences that calcium supplementation may decrease blood pressure and consequently cardiovascular disease, but they are not conclusive and there is no agreement in this respect. The aim of the present study was to assess the effect of supplementary calcium on systolic and diastolic blood pressure in healthy adult women aged 18–30 years. Materials and Methods: Seventy-five normotensive volunteers were randomly divided into two groups, the treatment group received 1000 mg/day calcium (four doses of 625 mg calcium carbonate) for 1 month and the control group received placebo (dextrose). Systolic and diastolic blood pressure was determined before and after intervention in supine position after 10 min of rest. Results: The mean daily calcium intake from food was 773.9 mg in treatment and 721 mg in control group (no significant difference) but in both the groups dietary calcium intake was less than the recommended dietary allowance: After calcium supplementation, the mean change of systolic blood pressure was not significant in the two groups, but diastolic blood pressure reduced in treatment group and increased in control group (−4.9 vs 2.6 mmHg) (P < 0.05). Conclusions: These results suggest that, calcium supplementation does not have any effect on systolic blood pressure of our volunteers but can decrease diastolic blood pressure significantly and therefore it seems that calcium supplementation may be useful for people with increased diastolic blood pressure, especially for those who receive less calcium than recommended dietary allowance. PMID:26430694

  20. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

    Full Text Available Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1 is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for

  1. Long-Term Blocking of Calcium Channels in mdx Mice Results in Differential Effects on Heart and Skeletal Muscle

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Blain, Alison; Greally, Elizabeth;

    2011-01-01

    calcium ions to enter the cell. The objective of this study was to investigate the effect of chronically blocking calcium channels with the aminoglycoside antibiotic streptomycin from onset of disease in the mdx mouse model of Duchenne muscular dystrophy (DMD). Treatment in utero onwards delayed onset...... in older mice. However, streptomycin treatment did not show positive effects in diaphragm or heart muscle, and heart pathology was worsened. Thus, blocking calcium channels even before disease onset does not prevent dystrophy, making this an unlikely treatment for DMD. These findings highlight...

  2. The effects of the β1 antagonist, metoprolol, on methamphetamine-induced changes in core temperature in the rat.

    Science.gov (United States)

    Harrell, Ricki; Speaker, H Anton; Mitchell, Scott L; Sabol, Karen E

    2015-11-16

    Methamphetamine (METH) results in hyperthermia or hypothermia depending on environmental conditions. Here we studied the role of the β1 adrenergic receptor in mediating METH's temperature effects. Core temperature measurements were made telemetrically over a 7.5h session, two days/week, in test chambers regulated at either 18°C, 24°C, or 30°C ambient temperature. Rats were treated with the β1 antagonist metoprolol (5.0, 10.0, and 15.0mg/kg) alone (Experiment 1), or in combination with 5.0mg/kg METH (Experiment 2). In experiment 3, we combined a lower dose range of metoprolol (0.75, 1.5, and 3.0mg/kg) with 5.0mg/kg METH at 18°C and 30°C. Confirming prior findings, METH alone resulted in hyperthermia in warm (30°) and hypothermia in cool environments (18°C). Metoprolol alone induced small but significant increases in core temperature. In combination, however, metoprolol reduced METH-induced changes in core temperature. Specifically, at 30°C, 3.0, 5.0, 10.0, and 15.0mg/kg metoprolol decreased METH-induced hyperthermia; at 18°C, all six doses of metoprolol enhanced METH-induced hypothermia. Our metoprolol findings suggest that one component of METH's temperature effects involves increasing core temperature at all ambient conditions via β1 receptors. Since β receptors are involved in brown adipose tissue (BAT)-mediated thermogenesis, skeletal muscle-mediated thermogenesis, heart rate, and the metabolism of glucose and lipids, we discuss each of these as possible mechanisms for metoprolol's effects on METH-induced changes in core temperature. PMID:26388403

  3. Antagonistic Effects of Fertilizer on Photochemical Efficiency of Hibiscus cannabinus L. (Kenaf Planted on Beach Ridges Interspersed with Swales Soil

    Directory of Open Access Journals (Sweden)

    Mohd-Hazimy Yusoff

    2011-01-01

    Full Text Available Problem statement: Hibiscus cannabinus L. or Kenaf is a highly productive, warmseasonal C3 annual crop and is one of the potential candidates to substitute kenaf fiber as raw product for pulp and paper production. It survives well on less fertile soils including those of Beach Ridges Interspersed with Swales (BRIS soil. Approach: The objective of this study was to determine the effect of fertilizer on photochemical efficiency of H. cannabinus L. planted on BRIS soil using chlorophyll fluorescence technique. NPK with the ratio of 12:12:36 + 2MgO + TE (Trace-elements are mineral substances that act as an essential nutrients at a very low concentration and the micronutrient of the trace elements compositions are Boron, Copper, Iron, Manganese, Molybdenum and Zinc were used for fertilizer treatment. Three levels of fertilizer treatments were applied in three plots; high (1960 kg plot-1, medium (1260 kg plot-1 and low (700 kg plot-1 respectively each plot comprising 106, 000 plants and were planted in 20 lines. Photochemical efficiency in terms of Fv/Fm ratio was determined under water deficit condition, fertilizer toxicity and interaction of both factors. Results: Contrasting trends for photochemical parameters were observed between different fertilizer levels where antagonistic effects were found between the three fertilizer treatments. The mean values ranged for minimal fluorescence (Fo were from 256.27-273.06, maximal fluorescence (Fm were from 970-1110.5, variable fluorescence (Fv were from 705-854.23 and the ratio of Fv/Fm (photochemical efficiency were from 0.72-0.77, respectively. Hitherto, for stress level, percentage for the low fertilizer level was 23.5% as compared to medium with 26.8 and 27.6% for high fertilizer level. Conclusion: The present study revealed that an appropriate amount of fertilizer is required to maximize the yield production cost effectively.

  4. The effects of the β1 antagonist, metoprolol, on methamphetamine-induced changes in core temperature in the rat.

    Science.gov (United States)

    Harrell, Ricki; Speaker, H Anton; Mitchell, Scott L; Sabol, Karen E

    2015-11-16

    Methamphetamine (METH) results in hyperthermia or hypothermia depending on environmental conditions. Here we studied the role of the β1 adrenergic receptor in mediating METH's temperature effects. Core temperature measurements were made telemetrically over a 7.5h session, two days/week, in test chambers regulated at either 18°C, 24°C, or 30°C ambient temperature. Rats were treated with the β1 antagonist metoprolol (5.0, 10.0, and 15.0mg/kg) alone (Experiment 1), or in combination with 5.0mg/kg METH (Experiment 2). In experiment 3, we combined a lower dose range of metoprolol (0.75, 1.5, and 3.0mg/kg) with 5.0mg/kg METH at 18°C and 30°C. Confirming prior findings, METH alone resulted in hyperthermia in warm (30°) and hypothermia in cool environments (18°C). Metoprolol alone induced small but significant increases in core temperature. In combination, however, metoprolol reduced METH-induced changes in core temperature. Specifically, at 30°C, 3.0, 5.0, 10.0, and 15.0mg/kg metoprolol decreased METH-induced hyperthermia; at 18°C, all six doses of metoprolol enhanced METH-induced hypothermia. Our metoprolol findings suggest that one component of METH's temperature effects involves increasing core temperature at all ambient conditions via β1 receptors. Since β receptors are involved in brown adipose tissue (BAT)-mediated thermogenesis, skeletal muscle-mediated thermogenesis, heart rate, and the metabolism of glucose and lipids, we discuss each of these as possible mechanisms for metoprolol's effects on METH-induced changes in core temperature.

  5. Effects of Propranolol, a β-noradrenergic Antagonist, on Memory Consolidation and Reconsolidation in Mice.

    Science.gov (United States)

    Villain, Hélène; Benkahoul, Aïcha; Drougard, Anne; Lafragette, Marie; Muzotte, Elodie; Pech, Stéphane; Bui, Eric; Brunet, Alain; Birmes, Philippe; Roullet, Pascal

    2016-01-01

    Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD). However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10 mg/kg) affected memory consolidation in non-aversive tasks (object recognition and object location) but not in moderately (Morris water maze (MWM) to highly (passive avoidance, conditioned taste aversion) aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks); propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event.

  6. Effects of propranolol, a β-noradrenergic antagonist, on memory consolidation and reconsolidation in mice

    Directory of Open Access Journals (Sweden)

    Hélène eVillain

    2016-03-01

    Full Text Available Memory reconsolidation impairment using the β-noradrenergic receptor blocker propranolol is a promising novel treatment avenue for patients suffering from pathogenic memories, such as post-traumatic stress disorder (PTSD. However, in order to better inform targeted treatment development, the effects of this compound on memory need to be better characterized via translational research. We examined the effects of systemic propranolol administration in mice undergoing a wide range of behavioral tests to determine more specifically which aspects of the memory consolidation and reconsolidation are impaired by propranolol. We found that propranolol (10mg/kg affected memory consolidation in non-aversive tasks (object recognition and object location but not in moderately (Morris water maze to highly (passive avoidance, conditioned taste aversion aversive tasks. Further, propranolol impaired memory reconsolidation in the most and in the least aversive tasks, but not in the moderately aversive task, suggesting its amnesic effect was not related to task aversion. Moreover, in aquatic object recognition and location tasks in which animals were forced to behave (contrary to the classic versions of the tasks; propranolol did not impair memory reconsolidation. Taken together our results suggest that the memory impairment observed after propranolol administration may result from a modification of the emotional valence of the memory rather than a disruption of the contextual component of the memory trace. This is relevant to the use of propranolol to block memory reconsolidation in individuals with PTSD, as such a treatment would not erase the traumatic memory but only reduce the emotional valence associated with this event.

  7. Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

    DEFF Research Database (Denmark)

    Edvinsson, Lars; Chan, Kayi Y; Eftekhari, Sajedeh;

    2010-01-01

    in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the α......CGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral...

  8. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist

    DEFF Research Database (Denmark)

    2015-01-01

    BACKGROUND: To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. METHODS: We created a genetic score combining the effects of alleles...... this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic......). FINDINGS: For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p = 9.3 × 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1.7%; p = 3.5 × 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD...

  9. Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

    Directory of Open Access Journals (Sweden)

    Deokhoon Park

    2013-05-01

    Full Text Available Ultraviolet (UV radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs formation, glutathione (GSH depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

  10. Antioxidant effect of T-type calcium channel blockers in gastric injury.

    Science.gov (United States)

    Bilici, Dilek; Banoğlu, Z Nur; Kiziltunç, Ahmet; Avci, Bahattin; Ciftçioğlu, Akif; Bilici, Sefa

    2002-04-01

    It is known that calcium ion has an important role in the cellular function. For this reason, calcium channel blockers may have a protective action against gastric injury which is induced by various stimuli. In this study, the influence of mibefradil on ethanol-induced gastric injury was investigated in rats. Mibefradil was given at a dose 50 mg/kg intraperitoneally 30 min before administration of 1 ml absolute ethanol given by gavage. We compared this effect of mibefradil with that of omeprazol. Ethanol-induced mucosal damage was evaluated using three different approaches: analysis of biochemical parameters and pathologic and macroscopic investigation. It was found that pretreatment with mibefradil significantly reduced ethanol-induced macroscopic, pathologic, and biochemical changes in the gastric mucosa. In conclusion, it is speculated that this findings may prove important in the development of new and improved therapies for the treatment and prevention of gastric ulcers in humans. PMID:11991620

  11. Effect of Lanthanum(Ⅲ) on Cytosolic Free Calcium in Isolated Rabbit Mature Osteoclasts

    Institute of Scientific and Technical Information of China (English)

    Zhang Jinchao; Zhang Tianlan; Xu Shanjin; Wang Kui; Yu Shifeng; Yang Mengsu

    2005-01-01

    The effect of lanthanum(Ⅲ) (La3+) on cytosolic free calcium ([Ca2+]i) in isolated rabbit mature osteoclasts was studied with the employment of fluo-3/AM as an intracellular calcium-sensitive fluorescent probe by using a confocal laser scanning microscope. La3+ does not alter basal [Ca2+]i levels and cell spread area at the concentration of 1.00×10-8 mol·L-1. However, La3+ at higher concentrations ( 1.00×10-5 and 1.00×10-7 mol·L-1) decreases [Ca2+]i levels and cell spread area, and greater decreases are observed for the higher concentrations of La3+. Since [Ca2+]i affects cytoskeleton and the adhesion properties of osteoclasts, our results seem to suggest that La3+ inhibit bone resorption by decreasing [Ca2+]i in rabbit mature osteoclasts.

  12. Mechanism for Alternating Electric Fields Induced-Effects on Cytosolic Calcium

    Institute of Scientific and Technical Information of China (English)

    LUO Ming-Yan; SONG Kun; ZHANG Xu; LEE Imshik

    2009-01-01

    In this work, from the point of calcium ions in the cytosol, we extend a Vm-[Ca2+]cyt model to explain the changes of action potential Vm of the plasma membrane and the calcium concentration in the cytosol [Ca2+]cyt under an alternating electric field in cells. An alternating external electric field may exert an oscillating force to each of the free electrolytes, existing on both sides of the plasma membrane. The mechanism for the alternating electric field induced-effects on Vm and [Ca2+]cyt is elucidated. The simulation results show a correlation between the changes of [Ca2+]cyt and the alternating electric field. When the numerical ratio between the intensity Eo(mV/m) and the frequency ν, (Hz) of the field was about 1-2, the [Ca2+]cyt signal is changed dramatically. The bioactive changes of [Ca2+]cyt appear at low frequency, in the range of 0-100 Hz.

  13. Organic acid effect on calcium uptake by the wheat roots

    Directory of Open Access Journals (Sweden)

    Fabrize Caroline Nunes

    2009-02-01

    Full Text Available This work evaluated the effect of the natural organic acids on the uptake of Ca by the wheat roots in a hydroponic solution. The following organic acids were evaluated: citric, oxalic, tartaric, malic, malonic, maleic, DL-malic, p-hydroxybenzoic, aconitic, and salicilic. The organic acids neither enhanced the root growth nor increased Ca uptake. The salicilic and malic acids were highly toxic and decreased the root growth. The citric, tartaric, maleic, aconitic, and salicilic decreased the Ca uptake by the roots due to their higher capacity to form the stable complexes with Ca in solution at pH 6.0. Decreasing the Ca valence from Ca++ to CaL+ or CaL2(0 through the organic ligand complexation reactions decreased the Ca uptake. The results suggested that the wheat roots do not absorb Ca-organic complexes.Ácidos orgânicos possuem grupos funcionais com cargas negativas que complexam íons metálicos em solução. Este trabalho avaliou o efeito de ácidos orgânicos naturais na absorção de Ca pelas raízes de trigo. Foram avaliados os seguintes ácidos orgânicos: cítrico, oxálico, tartarico, málico, malônico, maleico, DL-málico, p-hidroxibenzoico, aconítico e salicílico. Os ácidos orgânicos não estimularam o crescimento das raízes e não aumentaram a absorção de Ca. Os ácidos salicílico e maleico diminuíram drasticamente o crescimento radicular. Os ácidos cítrico, tartárico, maleico, aconítico e salicílico diminuíram a absorção de Ca pelas raízes devido à maior capacidade de formar complexos estáveis com Ca em solução no pH 6,0. A redução da valência de Ca++ para CaL+ e CaL2(0, através das reações de complexação, diminuiu a absorção de Ca pelas raízes. Os resultados sugerem que os complexos de Ca-orgânico não são absorvidos pelas raízes de trigo.

  14. Effects of dopamine agonists and antagonists on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test.

    Science.gov (United States)

    Sams-Dodd, F

    1998-01-01

    Phencyclidine (PCP) can induce a model psychosis in humans that resembles an acute schizophrenic psychosis. In animal models of schizophrenia, PCP induces locomotor hyperactivity, stereotyped behaviour and social isolation, and the purpose of the present study was to describe the ability of dopamine agonists and antagonists to mimic or interact with these PCP-induced behaviours in rats. The compounds were administered daily for 3 days in combination with vehicle or 2.0 mg/kg PCP and the rats were tested in the social interaction test on the last day of drug administration. The study showed that D1-agonists with relative differences in efficacy at the DA-stimulated adenylate cyclase had limited effects on the PCP-induced behaviours, whereas the D1-antagonist SCH 23391 could alleviate the PCP-induce social isolation following daily treatment for 3 days. However, following long-term treatment for 21 days, the rats develop tolerance to this effect. These data thus suggested that the D1-receptor system only had a modulatory effect on PCP. In contrast, the D2-receptor family may be more directly involved, because the D2/D3/D4-agonist quinpirole could mimic and potentiate the PCP-induced deficits in social behaviour, and the D2/D3-antagonist (-)sulpiride could alleviate the PCP-induced stereotyped behaviour and social isolation. However, a D4-antagonist did not affect the behaviour of vehicle- and PCP-treated rats, suggesting that this system plays a less direct role in the behavioural effects of PCP. In general, however, the effects of SCH 23391, quinpirole and (-)sulpiride on the PCP-induced behaviours were mirrored in the vehicle-treated control groups and it is therefore possible that non-specific effects may have been important.

  15. Beyond situational ambiguity in peer conflict: unique and combined effects of cues from an antagonist and a best friend.

    Science.gov (United States)

    Smith-Schrandt, Heather L; Ojanen, Tiina; Gesten, Ellis; Feldman, Marissa A; Calhoun, Casey D

    2011-01-01

    In accord with increasing recognition of the situation specificity of childhood social behaviors, individual and contextual differences in children's responses to potential peer conflict were examined (hostile attribution, behavioral strategies, and affective reactions; N = 367, 9-12 years, 197 girls). Situational cues from 2 sources, the antagonist and a witnessing best friend, were designed to suggest the antagonist's intentions. Multilevel modeling indicated that children's responses generally varied more according to cues from the antagonist than friend, but the latter also affected responses, especially when conflicting with other situational information. Cognitive and affective responses were also influenced by gender, social goals, friendship quality, and self-efficacy for peer interaction. Findings provide theoretical insight on the context of peer conflict. PMID:22023144

  16. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    AbdulQader, Sarah Talib [School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Department of Pedodontic and Preventive Dentistry, College of Dentistry, University of Baghdad, Baghdad (Iraq); Kannan, Thirumulu Ponnuraj, E-mail: kannan@usm.my [School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Rahman, Ismail Ab [School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia); Ismail, Hanafi [School of Materials and Minerals Resource Engineering, Universiti Sains Malaysia, 14300 Penang (Malaysia); Mahmood, Zuliani [School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2015-04-01

    Calcium phosphate (CaP) scaffolds have been widely and successfully used with osteoblast cells for bone tissue regeneration. However, it is necessary to investigate the effects of these scaffolds on odontoblast cells' proliferation and differentiation for dentin tissue regeneration. In this study, three different hydroxyapatite (HA) to beta tricalcium phosphate (β-TCP) ratios of biphasic calcium phosphate (BCP) scaffolds, BCP20, BCP50, and BCP80, with a mean pore size of 300 μm and 65% porosity were prepared from phosphoric acid (H{sub 2}PO{sub 4}) and calcium carbonate (CaCO{sub 3}) sintered at 1000 °C for 2 h. The extracts of these scaffolds were assessed with regard to cell viability and differentiation of odontoblasts. The high alkalinity, more calcium, and phosphate ions released that were exhibited by BCP20 decreased the viability of human dental pulp cells (HDPCs) as compared to BCP50 and BCP80. However, the cells cultured with BCP20 extract expressed high alkaline phosphatase activity and high expression level of bone sialoprotein (BSP), dental matrix protein-1 (DMP-1), and dentin sialophosphoprotein (DSPP) genes as compared to that cultured with BCP50 and BCP80 extracts. The results highlighted the effect of different scaffold ratios on the cell microenvironment and demonstrated that BCP20 scaffold can support HDPC differentiation for dentin tissue regeneration. - Highlights: • BCPs of different HA/β-TCP ratios influence cell microenvironment. • BCP20 decreases cell viability of HDPCs as compared to BCP50 and BCP80. • HDPCs cultured with BCP20 express highest ALP activity. • HDPCs cultured with BCP20 up-regulate BSP, DMP-1 and DSPP gene expressions. • BCP20 can support HDPC differentiation for dentin tissue regeneration.

  17. Effect of calcium citrate on bone integration in a rabbit femur defect model

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Peng-Fei Nie; Xiu-Cui Li; Ferdinand An Rompis; Hang Huang; Hua Zhang; Zhong-Lin Mu; Lei Peng; Wei Wang; Qing-Yu Chen; Zhong-Qin Lin; Shao-Wen Cheng; Dong-Quan Kou; Xiao-Zhou Ying; Yue Shen; Xiao-Jie Cheng

    2012-01-01

    ABSTRACT Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (GroupA, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus6.0 software after animal was sacrificed at 4th(GroupA), 6th(GroupB) and8th(GroupC) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative4th and6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to2.0 mm. No statistical difference was observed when these defects were larger than2.0 mm at all healing periods except at the4th week.Conclusions: Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

  18. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells

    International Nuclear Information System (INIS)

    Calcium phosphate (CaP) scaffolds have been widely and successfully used with osteoblast cells for bone tissue regeneration. However, it is necessary to investigate the effects of these scaffolds on odontoblast cells' proliferation and differentiation for dentin tissue regeneration. In this study, three different hydroxyapatite (HA) to beta tricalcium phosphate (β-TCP) ratios of biphasic calcium phosphate (BCP) scaffolds, BCP20, BCP50, and BCP80, with a mean pore size of 300 μm and 65% porosity were prepared from phosphoric acid (H2PO4) and calcium carbonate (CaCO3) sintered at 1000 °C for 2 h. The extracts of these scaffolds were assessed with regard to cell viability and differentiation of odontoblasts. The high alkalinity, more calcium, and phosphate ions released that were exhibited by BCP20 decreased the viability of human dental pulp cells (HDPCs) as compared to BCP50 and BCP80. However, the cells cultured with BCP20 extract expressed high alkaline phosphatase activity and high expression level of bone sialoprotein (BSP), dental matrix protein-1 (DMP-1), and dentin sialophosphoprotein (DSPP) genes as compared to that cultured with BCP50 and BCP80 extracts. The results highlighted the effect of different scaffold ratios on the cell microenvironment and demonstrated that BCP20 scaffold can support HDPC differentiation for dentin tissue regeneration. - Highlights: • BCPs of different HA/β-TCP ratios influence cell microenvironment. • BCP20 decreases cell viability of HDPCs as compared to BCP50 and BCP80. • HDPCs cultured with BCP20 express highest ALP activity. • HDPCs cultured with BCP20 up-regulate BSP, DMP-1 and DSPP gene expressions. • BCP20 can support HDPC differentiation for dentin tissue regeneration

  19. Effects Due to Rhizospheric Soil Application of an Antagonistic Bacterial Endophyte on Native Bacterial Community and Its Survival in Soil: A Case Study with Pseudomonas aeruginosa from Banana.

    Science.gov (United States)

    Thomas, Pious; Sekhar, Aparna C

    2016-01-01

    Effective translation of research findings from laboratory to agricultural fields is essential for the success of biocontrol or growth promotion trials employing beneficial microorganisms. The rhizosphere is to be viewed holistically as a dynamic ecological niche comprising of diverse microorganisms including competitors and noxious antagonists to the bio-inoculant. This study was undertaken to assess the effects due to the soil application of an endophytic bacterium with multiple pathogen antagonistic potential on native bacterial community and its sustenance in agricultural soil. Pseudomonas aeruginosa was employed as a model system considering its frequent isolation as an endophyte, wide antagonistic effects reported against different phytopathogens and soil pests, and that the species is a known human pathogen which makes its usage in agriculture precarious. Employing the strain 'GNS.13.2a' from banana, its survival in field soil and the effects upon soil inoculation were investigated by monitoring total culturable bacterial fraction as the representative indicator of soil microbial community. Serial dilution plating of uninoculated control versus P. aeruginosa inoculated soil from banana rhizosphere indicated a significant reduction in native bacterial cfu soon after inoculation compared with control soil as assessed on cetrimide- nalidixic acid selective medium against nutrient agar. Sampling on day-4 showed a significant reduction in P. aeruginosa cfu in inoculated soil and a continuous dip thereafter registering >99% reduction within 1 week while the native bacterial population resurged with cfu restoration on par with control. This was validated in contained trials with banana plants. Conversely, P. aeruginosa showed static cfu or proliferation in axenic-soil. Lateral introduction of soil microbiome in P. aeruginosa established soil under axenic conditions or its co-incubation with soil microbiota in suspension indicated significant adverse effects by

  20. Moving and academic learning are not antagonists: acute effects on executive function and enjoyment.

    Science.gov (United States)

    Vazou, Spyridoula; Smiley-Oyen, Ann

    2014-10-01

    Classroom-based physical activity is a new approach aiming to improve both physical activity levels and academic achievement. This study investigated the acute effect of a 10-min bout of aerobic physical activity integrated with math practice, compared with a seated math practice, on executive function and enjoyment among normal-weight (n = 24) and overweight children (n = 11). Thirty-five typically developing prepubescent children (10.55 ± 0.74 years) completed a session of physical activity integrated with math practice and a seated math practice session in counterbalanced order. Results showed that following integrated physical activity, the response time in the Standard Flanker improved more than after seated practice. Among the overweight children, physical activity benefitted performance in the Standard Flanker by preventing the decline associated with seated practice. Children enjoyed the physical activity practice more than the seated practice. These findings suggest that integrating physical activity with academic instruction may be a realistic strategy for promoting physical activity because it may facilitate, not antagonize, executive function. PMID:25356611

  1. Effects of leukotriene receptor antagonist on chronic obstractive pulmonary disease induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    卜小宁; 王辰; 庞宝森

    2003-01-01

    Objectives To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.Methods Eleven cases of chronic cor pulmonale at acute exacerbation were examinted using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E4 (LTE4) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Artarial and mixed venous blood gas analyses were done correspondingly.Results The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE4 and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP. Conclusions Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.

  2. Antagonistic effects of humic acid and iron oxyhydroxide grain-coating on biochar nanoparticle transport in saturated sand.

    Science.gov (United States)

    Wang, Dengjun; Zhang, Wei; Zhou, Dongmei

    2013-05-21

    Biochar land application may result in multiple agronomic and environmental benefits (e.g., carbon sequestration, improving soil quality, and immobilizing environmental contaminants). However, our understanding of biochar particle transport is largely unknown in natural environments with significant heterogeneity in solid (e.g., patches of iron oxyhydroxide coating) and solution chemistry (e.g., the presence of natural organic matter), which represents a critical knowledge gap in assessing the environmental impact of biochar land application. Transport and retention kinetics of nanoparticles (NPs) from wheat straw biochars produced at two pyrolysis temperatures (i.e., 350 and 550 °C) were investigated in water-saturated sand columns at environmentally relevant concentrations of dissolved humic acid (HA, 0, 1, 5, and 10 mg L(-1)) and fractional surface coverage of iron oxyhydroxide coatings on sand grains (ω, 0.16, 0.28, and 0.40). Transport of biochar NPs increased with increasing HA concentration, largely because of enhanced repulsive interaction energy between biochar NPs and sand grains. Conversely, transport of biochar NPs decreased significantly with increasing ω due to enhanced electrostatic attraction between negatively charged biochar NPs and positively charged iron oxyhydroxides. At a given ω of 0.28, biochar NPs were less retained with increasing HA concentration due to increased electrosteric repulsion between biochar NPs and sand grains. Experimental breakthrough curves and retention profiles were well described using a two-site kinetic retention model that accounted for Langmuirian blocking or random sequential adsorption at one site. Consistent with the blocking effect, the often observed flat retention profiles stemmed from decreased retention rate and/or maximum retention capacity at a higher HA concentration or smaller ω. The antagonistic effects of HA and iron oxyhydroxide grain-coating imparted on the mobility of biochar NPs suggest that

  3. Beneficial effects montelukast, cysteinyl-leukotriene receptor antagonist, on renal damage after unilateral ureteral obstruction in rats

    Directory of Open Access Journals (Sweden)

    Alper Otunctemur

    2015-04-01

    Full Text Available Introductıon Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO in rats. Mateirıals and Methods 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day. After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO, malondialdehyde(MDA and reduced glutathione(GSH levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA. Results There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005. Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005. Conclusıon We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.

  4. Effect of dietary calcium and 1,25-(OH)2D3 on the expression of calcium transport genes in calbindin-D9k and -D28k double knockout mice.

    Science.gov (United States)

    Ko, Sang-Hwan; Choi, Kyung-Chul; Oh, Goo Taeg; Jeung, Eui-Bae

    2009-02-01

    The phenotypes of calbindin-D9k (CaBP-9k) and -28k (CaBP-28k) single knockout (KO) mice are similar to wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we generated CaBP-9k/CaBP-28k double knockout (DKO) mice in order to investigate the importance of CaBP-9k and CaBP-28k in active calcium processing. Under normal dietary conditions, DKO mice did not exhibit any changes in phenotype or the expression of active calcium transport genes as compared to WT or CaBP-28k KO mice. Under calcium-deficient dietary conditions, the phenotype and expression of calcium transport genes in CaBP-28k KO mice were similar to WT, whereas in DKO mice, serum calcium levels and bone length were decreased. The intestinal and renal expression of transient receptor potential vanilloid member 6 (TRPV6) mRNA was significantly decreased in DKO mice fed a calcium-deficient diet as compared to CaBP-28k KO or WT mice, and DKO mice died after 4 weeks on a calcium-deficient diet. Body weight, bone mineral density (BMD) and bone length were significantly reduced in all mice fed a calcium and 1,25-(OH)(2)D(3)-deficient diet, as compared to a normal diet, and none of the mice survived more than 4 weeks. These results indicate that deletion of CaBP-28k alone does not affect body calcium homeostasis, but that deletion of CaBP-9k and CaBP-28k has a significant effect on calcium processing under calcium-deficient conditions, confirming the importance of dietary calcium and 1,25-(OH)(2)D(3) during growth and development.