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Sample records for calcium antagonistic effects

  1. Antagonist effects of calcium on borosilicate glass alteration

    Energy Technology Data Exchange (ETDEWEB)

    Mercado-Depierre, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Angeli, F., E-mail: frederic.angeli@cea.fr [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Frizon, F. [CEA Marcoule, DTCD SECM LP2C, 30207 Bagnols sur Cèze (France); Gin, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France)

    2013-10-15

    Graphical abstract: Display Omitted -- Highlights: •Kinetic study of glass alteration is investigated in calcium-enriched solutions. •New insights into silicon–calcium interactions in glass/cement systems are proposed. •Glass alteration is controlled by pH, Ca concentration and reaction progress. •Evidence of antagonist effects according to the importance of these parameters. -- Abstract: Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage.

  2. Diverse effects of calcium antagonists on glomerular hemodynamics.

    Science.gov (United States)

    Arima, S; Ito, S; Omata, K; Tsunoda, K; Yaoita, H; Abe, K

    1996-06-01

    This study examined the direct effects of calcium antagonists on glomerular hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-Arts) were microperfused in vitro at constant pressure. Ef-Arts were perfused from the distal end of Af-Art through the glomerulus. Increasing doses (10(-10) to 10(-7) M) of nifedipine (Nif), nicardipine (Nic) or manidipine (Man) were added into the lumen of Af- or Ef-Arts preconstricted (by about 40%) with norepinephrine. Although Nif and Nic dilated Af-Arts in a dose-dependent manner, they did not cause any dilation in Ef-Arts. In contrast, Man dilated both Af- and Ef-Arts in a dose dependent manner; Man at 10(-7) M dilated Af- and Ef-Arts by 71 +/- 12% (N = 7) and 38 +/- 3% (N = 6), respectively. Although Man's dilator effect on Ef-Art was not affected by inhibiting nitric oxide (NO) synthesis (N = 6), it was markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man at 10(-7) M, N = 5). These results demonstrate that in addition to dilating Af-Art, Man, but not Nif or Nic, dilates Ef-Art through a glomerulus-derived vasodilator(s) other than NO. Such diverse actions should be taken into consideration when calcium antagonists are used in the treatment of patients with cardiovascular and renal diseases.

  3. Effects of calcium antagonists on hypertension and diastolic function ...

    African Journals Online (AJOL)

    Calcium antagonists are known to decrease blood pressure acutely and chronically in hypertensive patients with hypertensive heart disease, and also to improve their systolic function. However, disorders of diastolic function may occur early in hypertensive heart disease. The improvement of diastolic function by nifedipine ...

  4. Calcium-antagonist effects of quercetin on aortic smooth muscle.

    Science.gov (United States)

    Morales, M A; Lozoya, X

    1994-08-01

    Relaxation induced by quercetin was studied on aortic rings depolarized with KCl and on Ca2+ dependent aortic contraction. Quercetin's actions as a cyclooxygenase inhibitor were compared with those of indomethacin. To determine the possible effects of quercetin on internal Ca2+ mobilization, it was assayed on aortic muscle contracted with caffeine. Quercetin relaxes aortic smooth muscle contracted with KCl (RC50 = 1.8 x 10(-4) M) and induces a rightward displacement of Ca2+ curves. The relaxation induced by quercetin is higher than that produced by indomethacin, suggesting that its action is independent of cyclooxygenase inhibition. Caffeine-induced aortic contraction was not modified by quercetin, suggesting that its effect should not involve internal calcium modulation. Our results further support the thesis that the spasmolytic action of quercetin arises from its negative modulation of calcium entry to the smooth muscle.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Effects of manidipine and other calcium antagonists on rat renal arcuate arteries

    NARCIS (Netherlands)

    Pfaffendorf, M.; Mathy, M. J.; van Zwieten, P. A.

    1993-01-01

    We investigated the effect of 1,4-dihydropyridine calcium antagonists (nifedipine, nisoldipine, and manidipine) on serotonin (5-hydroxytryptamine [5-HT])- and KCl (120 mmol/L)-induced contractions of rat isolated renal arcuate arteries. The preparation showed the well-known biphasic response to

  7. Differential effects of calcium antagonist subclasses on markers of nephropathy progression.

    Science.gov (United States)

    Bakris, George L; Weir, Matthew R; Secic, Michelle; Campbell, Brett; Weis-McNulty, Annette

    2004-06-01

    Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential antiproteinuric effects. Proteinuria reduction is a correlate of the progression of renal disease. In an earlier systematic review, calcium antagonists were shown as effective antihypertensive drugs, but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency. A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria, with or without diabetes, and to determine whether these differential effects translate into altered progression of nephropathy. Studies included in the review had to be randomized clinical trials with at least 6 months of treatment, include a DCA or NDCA treatment arm, have one or more renal end points, and have been initiated after 1986. Summary data were extracted from 28 studies entered into two identical but separate databases, which were compared and evaluated by independent reviewers. The effects of each drug class on blood pressure (N= 1338) and proteinuria (N= 510) were assessed. After adjusting for sample size, study length, and baseline value, there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs, despite no significant differences in blood pressure reduction or presence of diabetes. This analysis supports (1) similar efficacy between subclasses of calcium antagonists to lower blood pressure, and (2) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes. Based on these findings, NDCAs, alone or in combination with an angiotensin-converting enzyme

  8. 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

  9. Vascular effects of calcium antagonists: implications for hypertension and other risk factors for coronary heart disease

    NARCIS (Netherlands)

    van Zwieten, P. A.

    1989-01-01

    All calcium antagonists (CAs) so far developed are vasodilators, and this property is a most important component of their therapeutic potency in hypertension and angina pectoris. At a cellular level, the specific interaction of CAs with transmembranous calcium fluxes involves both potential and

  10. Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats

    NARCIS (Netherlands)

    Heijnis, J. B.; Mathy, M. J.; van Zwieten, P. A.

    1991-01-01

    The purpose of this study was to examine the effects of several calcium antagonistic drugs on left ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the

  11. Calcium antagonists protect mice against lethal doses of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Floersheim, G.L. (University Hospitals, Basel (Switzerland). Dept. of Research)

    1992-11-01

    Currently available radioprotectors are poorly tolerated in man and the general use of aminothiol radioprotectors is compromised by side-effects. In a search for less toxic radioprotective agents, diltiazem, a calcium antagonist with a benzothiazepine structure, was found to protect mice against a lethal (LD[sub 100]) [gamma] radiation dose allowing survival of up to 93%. Dihydropyridine calcium antagonists such as nifedipine, nimodipine, isradipine and nitrendipine also provided radioprotection. Calcium antagonists might attenuate radiation-induced injury by inhibiting cellular calcium overload, subsequent to cell membrane damage caused by radiation-generated free radicals. In view of their good tolerance, calcium antagonists may be applied safely in situations of radiation exposure, including radiotherapy and internal radionuclide contamination. These calcium antagonists may also be viewed in other contexts where free radicals are implicated in pathological processes. (Author).

  12. 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...

  13. Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells.

    Science.gov (United States)

    Takara, Kohji; Matsubara, Mika; Yamamoto, Kazuhiro; Minegaki, Tetsuya; Takegami, Shigehiko; Takahashi, Minoru; Yokoyama, Teruyoshi; Okumura, Katsuhiko

    2012-03-01

    The effects of 9 calcium antagonists on ABCG2/BCRP-mediated resistance and transport were examined in HeLa and SN-38-resistant HeLa (HeLa/SN100) cells, overexpressing ABCG2/BCRP. Sensitivity to mitoxantrone, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly reversed by the coexistence of the calcium antagonists, except for diltiazem and verapamil. The accelerated transport activity of Hoechst33342, an ABCG2/BCRP substrate, in HeLa/SN100 cells was significantly decreased by the presence of the calcium antagonists, except for diltiazem, nifedipine or verapamil, returning to the level of HeLa cells. The present study classifies the calcium antagonists into 3 categories: strong (benidipine, felodipine, nicardipine, nisoldipine and nitrendipine), moderate (amlodipine and nifedipine) and weak (diltiazem and verapamil) inhibitors of ABCG2/BCRP.

  14. Calcium dependency of the AT1-receptor mediated effects in the rat portal vein: influence of calcium antagonists

    NARCIS (Netherlands)

    Zhang, J. S.; van Meel, J. C.; Pfaffendorf, M.; Zhang, J.; van Zwieten, P. A.

    1994-01-01

    The calcium dependency of AT1-receptor mediated contractions was studied in isolated rat portal vein preparations. The spontaneous phasic contractile force of the rat portal vein was increased (ED50 = 1.76 mmol/l) and the frequency of contractions decreased by raising the extracellular calcium

  15. Effect of Angiotensin-Converting Enzyme Inhibitor/Calcium Antagonist Combination Therapy on Renal Function in Hypertensive Patients With Chronic Kidney Disease: Chikushi Anti-Hypertension Trial - Benidipine and Perindopril.

    Science.gov (United States)

    Okuda, Tetsu; Okamura, Keisuke; Shirai, Kazuyuki; Urata, Hidenori

    2018-02-01

    Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. Patients who failed to achieve the target blood pressure (systolic/diastolic: hypertensive patients with diabetic nephropathy, combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination.

  16. Pharmacological analysis of calcium antagonist receptors

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)(/sup 3/H)desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) (/sup 3/H)desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor.

  17. Calcium antagonists and the diabetic hypertensive patient

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P

    1993-01-01

    reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion...... nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease...

  18. Comparative effects of mibefradil and other calcium antagonists on resistance arteries of different end organs

    NARCIS (Netherlands)

    van der Lee, R.; Pfaffendorf, M.; van Zwieten, P. A.

    1999-01-01

    The biphasic contractile responses of rat isolated mesenteric, renal, coronary and basilar small arteries to potassium-induced depolarization were investigated. The tonic phase is assumed to be exclusively the result of L-type calcium channel (LCC) activation, whereas in the generation of the phasic

  19. The differential effect of calcium antagonists on the positive inotropic effects induced by calcium and monensin in cardiac preparations of rats and guinea-pigs

    NARCIS (Netherlands)

    Hugtenburg, J. G.; Mathy, M. J.; Beckeringh, J. J.; van Zwieten, P. A.

    1989-01-01

    It was the aim of the present study to gain more insight into the role of extracellular calcium and of calcium from intracellular sources in the development of contractile force in the mammalian heart. In rat Langendorff hearts the effect of nifedipine, verapamil, diltiazem, bepridil and lidoflazine

  20. Calcium antagonists: a ready prescription for treating infectious diseases?

    Science.gov (United States)

    Clark, Kevin B; Eisenstein, Edward M; Krahl, Scott E

    2013-01-01

    Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca(2+) molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca(2+), and downstream binding proteins and sensors of Ca(2+)-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis.

  1. Different effects of dihydropyridine calcium channel antagonists on CYP3A4 enzyme of human liver microsomes.

    Science.gov (United States)

    Xia, Zongling; Wang, Mingli; Zou, Sulan; Chen, Rong

    2012-09-01

    The present study investigated inhibitory effects of 1,4-dihydropyridines (1,4-DHPs) calcium channel antagonists (1,4-DHP-CCAs) on cytochromeP450 3A4 (CYP3A4) of human liver microsomes and further explored importance of 1,4-DHPs molecular structural descriptors. Partial Least Squares method was applied to probe the quantitative relationships between the 1,4-DHPs molecular structural descriptors and its inhibitory actions, which demonstrated that different 1,4-DHP-CCAs could inhibit CYP3A4 enzyme's activity differently. The K (i) values of nicardipine, lercandipine, cilnidipine, nitrendipine, lacidipine, nifedipine, felodipine were 10.13, 10.17, 11.44, 23.90, 29.34, 29.06 and 32.64 μmol L⁻¹, respectively. It is suggested that the 1,4-DHPs molecular structural descriptors are the most important for its inhibitory effects based on the quantitative structure-activity relationship (QSAR) formula. The LogP was positively correlated to the K (i), whereas molecular weight and molecule volume were negatively correlated. It is concluded that analysis of K (i) of 1,4-DHPs derivatives on the CYP3A4 activity may apply for the QSAR formula at the initial stage of clinical application of new drugs.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A comparison of the cardioprotective effects of calcium antagonists from different classes upon ischaemic damage in the guinea-pig working heart.

    Science.gov (United States)

    Hugtenburg, J G; Mathy, M J; Veldsema-Currie, R D; Boddeke, H W; Beckeringh, J J; van Zwieten, P A

    1989-07-01

    The cardioprotective effects of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and the coronary vasodilator dipyridamole were evaluated in the guinea-pig working heart with respect to cardiac function and high energy phosphate content after 45 min of global ischaemia and 25 min of reperfusion. All drugs, with the exception of dipyridamole, induced a negative inotropic effect, which resulted in a decrease of the aortic pressure (AoP), of its first derivative dAoP/dt and the cardiac output. To compare the anti-ischaemic effect of the calcium antagonists, concentrations were selected that reduced the dAoP/dt by 10% (EC10) and 30% (EC30), respectively. With the exception of nifedipine at the EC10 and bepridil and CERM 11956 at the EC30, perfusion with the calcium antagonists and dipyridamole (3 mumol/l) improved the recovery of contractile function after global ischaemia and reperfusion to a value between 60 and 80% of the controls in normoxic hearts. Pretreatment with nifedipine, verapamil, diltiazem, lidoflazine and mioflazine, but not with bepridil, CERM 11956 and dipyridamole led to slightly increased ATP levels in ischaemic hearts as compared to the control value in ischaemic hearts. After subsequent reperfusion for 25 min, for all drugs, ATP levels were further enhanced to 50% of the level in normoxic hearts; phosphocreatine levels reached normoxic values. In particular at the EC30, the effects of calcium antagonists on cardiac function varied in accordance with their known pharmacological and physiological profile. However, there appeared to exist no direct relationship between their beneficial effects on contractile activity and those on the levels of high energy phosphates after ischaemia and reperfusion.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Simple sensitive radioreceptor assay for calcium antagonist drugs

    Energy Technology Data Exchange (ETDEWEB)

    Gould, R.J.; Murphy, K.M.M.; Snyder, S.H.

    1983-12-26

    A radioreceptor assay for calcium channel antagonist drugs described here is based on the ability of these drugs to affect /sup 3/H-nitrendipine binding to calcium channels. All the known calcium channel antagonists may be assayed in this manner. The assay can detect 10-100 nM nimodipine, 10-100 nM nifedipine, 3-30 ..mu..M prenylamine, 0.1 - 1.0 ..mu..M verapamil and 3-30 ..mu..M diltiazem. These values cover the range of concentrations of calcium channel antagonists that are clinically important. As the radioreceptor assay detects active metabolites as well as the parent drugs, it should prove a useful adjunct in cardiovascular therapy. The method is more reproducible, simpler and less expensive than other methods such as high pressure liquid chromatography.

  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...

  7. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists.

    Science.gov (United States)

    Weir, M R; Rosenberger, C; Fink, J C

    2001-09-01

    Combination therapy is required in many patients to achieve goal blood pressure (BP). Calcium antagonists are highly effective antihypertensive drugs in a broad range of demographic groups. Yet, higher doses are associated with an increased frequency of lower extremity edema. The purpose of our open label, single-center clinical trial was to evaluate the use of concomitant pharmacologic therapies to attenuate the lower extremity edema associated with dihydropyridine calcium antagonists therapy using a water displacement technique. Forty-seven patients received 5 mg/day of oral amlodipine for a period of 6 weeks after a 4-week wash-out off of all antihypertensive medications to establish baseline BP. They were then randomized to receive either an additional 5 mg of amlodipine, 25 mg of hydrochlorothiazide (HCTZ), or 20 mg of benazepril for an additional 6 weeks. Blood pressure determinations and water displacement measurements were obtained at the end of the 4-week placebo wash-out period, after 6 weeks of 5 mg/day of oral amlodipine therapy, and after an additional 6 weeks of 5 mg of amlodipine and randomized drug therapy. Adjusted BP reductions (based on pretreatment BP) were -6.8/-3.8 mm Hg for the 10-mg amlodipine group, -9.9/-8.2 mm Hg for the amlodipine (5 mg)/HCTZ (25 mg) group, and -26.2/-16.4 mm Hg for the amlodipine (5 mg)/benazepril (20 mg) group (P increase in lower extremity edema water displacement in response to 5 mg/day of oral amlodipine therapy (36.2%). Adding 5 mg of amlodipine to a baseline of 5 mg of amlodipine resulted in no net change in lower extremity edema (+58.0 mL,+ 0.6% change, n=5). Adding 25 mg of HCTZ reduced lower extremity edema by a mean of 136.3 mL (-11.1% change, n=4). Benazepril reduced water displacement by 204.4 mL (-14.3% change, n=8). Our pilot study indicates that adding an angiotensin converting enzyme inhibitor to a dihydropyridine calcium channel blocker is the most effective way to not only reduce systolic and diastolic

  8. Can we use calcium antagonist better in antihypertensive therapy? Circadian consideration.

    Science.gov (United States)

    Zhang, W

    1996-01-01

    On the basis of theoretical reasoning, it has been thought that calcium antagonists should be better than other classes of antihypertensive agents. However in several large scale clinical trials, the benefits have been smaller than expected. Meta-analysis has indicated that dihydropyridine calcium antagonists failed to reduce cardiac mortality and morbidity. The reason for this is probably multifactorial. Reflex activation of the sympathetic nervous system (SNS) secondary to the reduction of blood pressure by calcium antagonists may play a very important role. It has been documented that the cardiovascular system has circadian rhythm and that most of the cardiovascular events in the general population happen in the morning, when the SNS is at its most active. Thus intrinsic activation of SNS set by circadian rhythm and extrinsic activation secondary to direct vasodilatation induced by calcium antagonists may overlap, which could increase cardiovascular risks and therefore result in poor clinical outcome. Antihypertensive therapy with calcium antagonists could be improved if it were possible to avoid the reflex activation and inhibit the intrinsic activation of SNS. A new chronotherapy is suggested, of which the basic principle is: to choose two classes of drugs with different mechanisms of action and use them at different periods of time during the day. By appropriate choice of the drugs and their acting time, not only the adverse effects, but also the risk during the vulnerable period could be reduced. Clinical research is needed to test this hypothesis.

  9. K022: Effect of combination therapy (ANG II antagonist, valsartan and a calcium channel blocker) in a hypertensive model of diabetic nephropathy

    OpenAIRE

    Allen, T.J.; Davis, B.J.; de Gasparo, M.; Cooper, M.E.

    2017-01-01

    Recently, it has been suggested that in the context of diabetes and hypertension, more aggressive blood pressure targets should be considered. To achieve these levels of blood pressure control, it is likely that combination therapy will need to be used. The present study has explored the role of the addition of either a dihydropyridine or a non-dihydropyridine calcium channel blocker (CCB) to Ang II antagonist based treatment in an experimental model of hypertension and diabetes. The doses ch...

  10. [The effect of ACE inhibitors, beta blockers and calcium antagonists on the responses to pressor stress tests in the elderly hypertensive patients].

    Science.gov (United States)

    Suzuki, Y; Kuwajima, I; Aono, T; Toyoshima, T; Ozawa, T

    1996-01-01

    The purpose of the study was to elucidate the effects of antihypertensive drugs on the hemodynamics in elderly hypertensive patients. Forty-two elderly hypertensives (mean 72 +/- 5 years) were given either ACE inhibitors (A group: perindopril in 10 and captopril in 4 cases), beta blockers (B group: arotinolol in 15 cases) or calcium antagonists (C group: nifedipine in 3 and nitrendipine in 10 cases) for 8-12 weeks. The responses to handgrip and mental arithmetic stress and cardiac functional changes were determined by echocardiography before and after the medications. The decrease in blood pressure at rest and on the stress tests was similar among the three groups, though the hemodynamic responses to the stress tests showed some differences. In the A group, no hemodynamic changes were seen either at rest or on the stress tests after the medication. In the B group, the heart rate and the cardiac output were decreased at rest, and the increase of them on the stress tests were diminished after the medication. On the contrary, the heart rate and the cardiac output were increased, and showed exaggerated responses on the stress tests in the C group. In conclusion, in antihypertensive treatment of elderly hypertensive patients it is important to consider the effects of the antihypertensive drugs on the hemodynamics, although the comparable decrease in blood pressure is expected.

  11. Renal protection in diabetes--an emerging role for calcium antagonists

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1997-01-01

    , 103 (SD 9) and 101 (SD 11) mm Hg in the two groups. Furthermore, a recent 5-year randomized open study in hypertensive noninsulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and ACE inhibition on the progression of nephropathy...

  12. 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......-ventricular diastolic function in patients with chronic stable angina. However, they affect different parameters and thus apparently act through different mechanisms....

  13. Effects of calcium antagonists on K(+)-induced contraction in isolated aorta from diabetic and age-matched control rats

    NARCIS (Netherlands)

    Heijnis, J. B.; van Zwieten, P. A.

    1993-01-01

    The effects of nifedipine, verapamil and diltiazem on K(+)-induced contraction were investigated in isolated aortic rings from diabetic and age-matched control rats. Six weeks after streptozotocin injection there was no significant difference between the maximum isometric contraction to KCl (80

  14. The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension : The VAMPHYRE study

    NARCIS (Netherlands)

    Lefrandt, JD; Heitmann, J; Sevre, K; Castellano, M; Hausberg, M; Fallon, M; Fluckiger, L; Urbigkeit, A; Rostrup, M; Agabiti-Rosei, E; Rahn, KH; Murphy, M; Zannad, F; de Kam, PJ; van Roon, AM; Smit, AJ

    2001-01-01

    The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine. (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg

  15. Adenosine versus intravenous calcium channel antagonists for supraventricular tachycardia.

    Science.gov (United States)

    Alabed, Samer; Sabouni, Ammar; Providencia, Rui; Atallah, Edmond; Qintar, Mohammed; Chico, Timothy Ja

    2017-10-12

    People with supraventricular tachycardia (SVT) frequently are symptomatic and present to the emergency department for treatment. Although vagal manoeuvres may terminate SVT, they often fail, and subsequently adenosine or calcium channel antagonists (CCAs) are administered. Both are known to be effective, but both have a significant side effect profile. This is an update of a Cochrane review previously published in 2006. To review all randomised controlled trials (RCTs) that compare effects of adenosine versus CCAs in terminating SVT. We identified studies by searching CENTRAL, MEDLINE, Embase, and two trial registers in July 2017. We checked bibliographies of identified studies and applied no language restrictions. We planned to include all RCTs that compare adenosine versus a CCA for patients of any age presenting with SVT. We used standard methodological procedures as expected by Cochrane. Two review authors independently checked results of searches to identify relevant studies and resolved differences by discussion with a third review author. At least two review authors independently assessed each included study and extracted study data. We entered extracted data into Review Manager 5. Primary outcomes were rate of reversion to sinus rhythm and major adverse effects of adenosine and CCAs. Secondary outcomes were rate of recurrence, time to reversion, and minor adverse outcomes. We measured outcomes by calculating odds ratios (ORs) and assessed the quality of primary outcomes using the GRADE approach through the GRADEproGDT website. We identified two new studies for inclusion in the review update; the review now includes seven trials with 622 participants who presented to an emergency department with SVT. All included studies were RCTs, but only three described the randomisation process, and none had blinded participants, personnel, or outcome assessors to the intervention given. Moderate-quality evidence shows no differences in the number of people reverting to

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

    Science.gov (United States)

    Pearigen, P D; Benowitz, N L

    1991-01-01

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

  17. Differential neuroprotective and anti-inflammatory effects of L-type voltage dependent calcium channel and ryanodine receptor antagonists in the substantia nigra and locus coeruleus.

    Science.gov (United States)

    Hopp, Sarah C; Royer, Sarah E; D'Angelo, Heather M; Kaercher, Roxanne M; Fisher, David A; Wenk, Gary L

    2015-03-01

    Neuroinflammation and degeneration of catecholaminergic brainstem nuclei occur early in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Neuroinflammation increases levels of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal calcium (Ca(+2)) homoeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Alterations in Ca(+2) channel activity in the SN and LC can lead to disruption of normal pacemaking activity in these areas, contributing to behavioral deficits. Here, we utilized an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose (0.25 μg/h) of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28 days. Rats were treated with either the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. LPS-infused rats had significant motor deficits in the accelerating rotarod task as well as abnormal behavioral agitation in the forced swim task and open field. Corresponding with these behavioral deficits, LPS-infused rats also had significant increases in microglia activation and loss of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra pars compacta (SNpc) and locus coeruleus (LC). Treatment with nimodipine or dantrolene normalized LPS-induced abnormalities in the rotarod and forced swim, restored the number of TH-immunoreactive cells in the LC, and significantly reduced microglia activation in the SNpc. Only nimodipine significantly reduced microglia activation in the LC, and neither drug increased TH immunoreactivity in the SNpc. These findings demonstrate that the Ca(+2) dysregulation in the LC and SN brainstem nuclei is differentially altered by chronic neuroinflammation. Overall, targeting Ca + 2 dysregulation may be an important target for ameliorating neurodegeneration in the SNpc and LC.

  18. LACK OF NEGATIVE INOTROPIC EFFECTS OF THE NEW CALCIUM-ANTAGONIST RO-40-5967 IN PATIENTS WITH STABLE ANGINA-PECTORIS

    NARCIS (Netherlands)

    PORTEGIES, MCM; SCHMITT, R; KRAAIJ, CJ; BRAAT, SHJG; GASSNER, A; HAGEMEIJER, F; POZENEL, H; PRAGER, G; VIERSMA, JW; VANDERWALL, EE; KLEINBLOESEM, CH; LIE, KI

    1991-01-01

    We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to receive a single oral dose of 50, 100, or 200 mg Ro

  19. Calcium gluconate infusion is as effective as the vascular endothelial growth factor antagonist cabergoline for the prevention of ovarian hyperstimulation syndrome

    Directory of Open Access Journals (Sweden)

    Nikita Naredi

    2013-01-01

    Full Text Available Background: Ovarian hyperstimulation syndrome (OHSS is an iatrogenic and potentially life-threatening disease process, which may occur in healthy young women undergoing controlled ovarian hyperstimulation for assisted reproduction. As the treatment is largely empirical, prevention forms the mainstay of management. Objective: The present study was aimed to evaluate the effectiveness of intravenous (IV calcium gluconate infusion in comparison to the dopamine agonist cabergoline (Cb2 in preventing OHSS in high risk patients undergoing assisted reproductive technique cycles. Materials and Methods: It was a comparative study wherein the 202 high risk patients undergoing in vitro-fertilization over a period of 18 months after meeting the strict inclusion and the exclusion criteria, were randomly divided into two groups (98 subjects in Group I and 104 in Group II. Women in Group I were administered IV calcium gluconate while the remaining 104 received the dopamine agonist Cb2. The 104 patients belonging to Group II were started Cb2 0.5 mg/day from the day of ovulation trigger and continued until the next 8 days while the 98 high risk patients from Group I were infused with 10 ml of 10% calcium gluconate solution in 200 ml physiologic saline within 30 min of ovum pick up and continued thereafter on day 1, day 2 and day 3. Results: The occurrence of OHSS was seen in only nine patients (in the calcium infusion group, when compared with 16 patients (9.2% vs. 15.4% who were administered Cb2, but it was not statistically significant. However, only one had severe OHSS in Group I, whereas two women were diagnosed as severe OHSS belonging to the Cb2 arm. Conclusion: Our results document that calcium infusion can effectively prevent severe OHSS and decreases OHSS occurrence rates when used for high-risk patients, but does not suggest its superiority over Cb2. With comparable success rates, either of them can be employed as a preventive strategy for OHSS.

  20. 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.

  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

    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 anesthet......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...

  2. APPLICATION OF CALCIUM ANTAGONISTS IN PREVENTION OF CARDIOVASCULAR COMPLICATIONS DURING CARDIAC SURGERY

    Directory of Open Access Journals (Sweden)

    S. V. Nedogoda

    2006-01-01

    Full Text Available Results of randomized clinical trials on the usage of calcium antagonists (CA in order to prevent perioperative complications during aortocoronary bypass procedure and operations on heart valves are analyzed. CA reduced the risk of perioperative myocardial infarctions and episodes of reversible myocardial ischemia. After angioplasty of coronary arteries CA (particularly amlodipine show positive effects on restenosis incidence and reduce about 3 times a number of repeated angioplasty and aortocoronary bypass operations. The use of CA was accompanied by more often need in heart electro stimulation without any subclass differences. It is also registered that nimodipine can strengthen intraoperative blood loss. It is concluded, that CA have significant evident base that allows recommending them to patients undertaken by cardiological surgery.

  3. Calcium antagonist radioprotectors do not reduce radiotherapeutic efficacy in three human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Floersheim, G.L. [Dept. of Research, Univ. Hospitals, Basel (Switzerland); Racine, C. [Dept. of Research, Univ. Hospitals, Basel (Switzerland)

    1995-07-01

    One Ewing`s sarcoma and 2 colon carcinomas were grown as xenografts in immunosuppressed mice. The mice were treated with diltiazem, nifedipine, nimodipine and nitrendipine. The effect of whole body {gamma}-radiation on the growth of the subcutaneously implanted tumors was assessed. Growth delay or regression of the tumors in mice treated with the calcium antagonists prior to irradiation was not reduced as compared to only irradiated controls. (orig.) [Deutsch] Ein Ewings-Sarkom und zwei Kolonkarzinome wurden als Xenotransplantate in immunsupprimierten Maeusen zum Wachstum gebracht. Zu den Pruefsubstanzen gehoerten Diltiazem, Nifedipin, Nimodipin und Nitrendipin. Beurteilt wurde der Effekt von {gamma}-Ganzkoerperbestrahlung auf das Wachstum der subkutan transplantierten Tumoren. Die Wachstumsverzoegerung oder Rueckbildung der transplantierten Tumoren durch die Bestrahlung wurde durch Vorbehandlung der Maeuse mit Calciumantagonisten im Vergleich zu nur bestrahlten Tieren nicht vermindert. (orig.)

  4. Antagonistic modulatory roles of magnesium and calcium on release of endothelium-derived relaxing factor and smooth muscle tone.

    Science.gov (United States)

    Gold, M E; Buga, G M; Wood, K S; Byrns, R E; Chaudhuri, G; Ignarro, L J

    1990-02-01

    The objective of this study was to elucidate the mechanisms associated with the reciprocal relation between magnesium and calcium on vascular smooth muscle tone in bovine pulmonary artery and vein. Rapid removal of magnesium from Krebs-bicarbonate medium used to bathe isolated rings of precontracted artery or vein caused transient endothelium- and calcium-dependent relaxation and cyclic GMP accumulation. Both responses were antagonized by oxyhemoglobin, methylene blue, or superoxide anion and were enhanced by superoxide dismutase. The transient relaxation was followed by sustained endothelium-independent contraction. Endothelium-denuded vascular rings contracted in response to extracellular magnesium depletion without alteration in cyclic GMP levels. The data suggest that vascular endothelium-derived nitric oxide is responsible for the calcium-dependent relaxation elicited by extracellular magnesium depletion. Indeed, in bioassay cascade studies, magnesium removal from the medium used to perfuse intact artery or vein enhanced the formation and/or release of an endothelium-derived relaxing factor by calcium-dependent mechanisms. In the absence of both extracellular magnesium and calcium, calcium readdition caused transient endothelium-dependent relaxation and cyclic GMP accumulation, and both responses were abolished by oxyhemoglobin or methylene blue. In the presence of magnesium, however, readdition of calcium to calcium-depleted medium caused only contractile responses. Addition of magnesium to calcium-containing medium consistently caused endothelium- and cyclic GMP-independent relaxation that was not altered by oxyhemoglobin or methylene blue. Thus, magnesium and calcium elicit reciprocal or mutually antagonistic effects at the levels of both endothelium-derived relaxing factor formation and/or release and smooth muscle contraction. This relation may be of physiological importance, and the possibility that a reduction in circulating magnesium levels could lead

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

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, R.J.; Appell, K.C.; Kilpatrick, B.F.; Proakis, A.G.; Nolan, J.C.; Walsh, D.A. (A. H. Robins Research Labs., Richmond, VA (USA))

    1991-01-01

    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.

  6. A comparison of the cardioprotective effects of calcium antagonists from different classes upon ischaemic damage in the guinea-pig working heart

    NARCIS (Netherlands)

    Hugtenburg, J. G.; Mathy, M. J.; Veldsema-Currie, R. D.; Boddeke, H. W.; Beckeringh, J. J.; van Zwieten, P. A.

    1989-01-01

    The cardioprotective effects of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and the coronary vasodilator dipyridamole were evaluated in the guinea-pig working heart with respect to cardiac function and high energy phosphate content after 45 min of global ischaemia

  7. Effects of Calcium Ion, Calpains, and Calcium Channel Blockers on Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Mitsuru Nakazawa

    2011-01-01

    Full Text Available Recent advances in molecular genetic studies have revealed many of the causative genes of retinitis pigmentosa (RP. These achievements have provided clues to the mechanisms of photoreceptor degeneration in RP. Apoptosis is known to be a final common pathway in RP and, therefore, a possible therapeutic target for photoreceptor rescue. However, apoptosis is not a single molecular cascade, but consists of many different reactions such as caspase-dependent and caspase-independent pathways commonly leading to DNA fractionation and cell death. The intracellular concentration of calcium ions is also known to increase in apoptosis. These findings suggest that calpains, one of the calcium-dependent proteinases, play some roles in the process of photoreceptor apoptosis and that calcium channel antagonists may potentially inhibit photoreceptor apoptosis. Herein, the effects of calpains and calcium channel antagonists on photoreceptor degeneration are reviewed.

  8. [Efficacy of calcium antagonists depending on the functional state of parathyroid glands in patients with hypertensive disease].

    Science.gov (United States)

    Iskenderov, B G; Burmistrova, L F; Sisina, O N; Lokhina, T V

    2009-01-01

    Hypotensive and cardioprotective effects of amlodipine (normodipine) were evaluated in 65 patients (35 men and 30 women) with grade II essential arterial hypertension treated with regard for calcium-controlling parathyroid function. 24 hour Holter monitoring, Doppler-cardiography, and blood PTH measurement were performed before and 6 months after the onset of therapy. The patients were divided into 3 groups depending on PTH levels (0-25, 26-50, and over 51 pg/ml). Changes of structural and functional cardiac parameters and AD were most prominent in group 3 in the form of decreased left ventricular hypertrophy, improved ventricular diastolic function, and marked hypotensive effect. The group was significantly different from group 1 in terms of these characteristics. Univariate analysis revealed correlation of PTH levels with left ventricular mass, mean daily systolic and diastolic AD, and left ventricular diastolic function. It is concluded that evaluation of calcium-regulating parathyroid function is necessary for optimization of antihypertensive therapy with calcium antagonists.

  9. 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.

  10. [Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Therapeutic value of treatment with calcium antagonists, hypervolemic hemodilution and induced arterial hypertension].

    Science.gov (United States)

    Hansen, D; Hannemann, L; Specht, M; Schaffartzik, W

    1995-04-01

    Only 53%-58% of patients with a subarachnoid haemorrhage (SAB) following the rupture of a cerebral aneurysm survive without neurological damage. Morbidity and mortality are closely related to the delayed ischaemic neurological deficit due to cerebral vasospasm. The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature. PATHOPHYSIOLOGY. In addition to other vasoactive substances in the blood, haemoglobin, which is released from lysed erythrocytes on the 2nd to 4th day after the haemorrhage, plays an important role in inducing vasospasm. An inflammatory angiopathy ensues, with complete resolution after 6-12 weeks. The cerebral blood flow (CBF) is reduced depending on the extent of vasospasm. Irreversible infarction may follow the decrease of CBF below a critical value. Severe vasospasm causes autoregulatory disturbances and reduced responsiveness of cerebral vessels to CO2. CALCIUM ANTAGONISTS. The calcium blocker nimodipine causes dilatation of small pial vessels with increased CBF. However, systemic vasodilation with the subsequent fall in blood pressure may limit the increase in CBF. Furthermore, it is known that nimodipine decreases intracellular calcium concentrations resulting in some protection against ischaemic cellular injury. Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm. HYPERVOLAEMIC HAEMODILUTION. Volume expansion and haemodilution to a hematocrit of 30%-33% is suggested to improve cerebral perfusion during vasospasm. The central venous and pulmonary capillary wedge pressures should be 10-12 mm Hg and 15-18 mm Hg, respectively. But there is no evidence of improved outcome with this measure, and pulmonary edema is a frequent side effect. However, impairment of

  11. Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.

    Science.gov (United States)

    Kanesaka, Y; Tokunaga, H; Iwashita, K; Fujimura, S; Naomi, S; Tomita, K

    2001-01-01

    Secondary hyperparathyroidism, one of the most frequently encountered disorders of the calcium homeostasis, is characterized by an increase in parathyroid epithelial (PT) cell number, which is crucial from a functional viewpoint. However, it is still unknown what factors are involved in PT cell proliferation. Endothelin-1 (ET-1), a vasoconstrictive peptide, has been shown to act as a mitogen in a variety of cell types. Rat PT cells are reported to synthesize ET-1 and possess its receptors. To test the hypothesis that ET-1 plays a role in PT cell proliferation, we used rat test subjects fed a low calcium diet for 8 weeks (low Ca rats). The number of the proliferating PT cells, measured by proliferating cell nuclear antigen immunostaining, was significantly increased, with striking immunoreactivity of ET-1 in the low Ca rats. An endothelin receptor antagonist, bosentan (100 mg/kg.day), prevented any increase in the proliferation of PT cells in the low Ca rats (14.3 +/- 2.7/1000 PT cells with no bosentan; 2.1 +/- 1.3 with bosentan; P hyperparathyroidism.

  12. 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.

  13. The cardioprotective effects of mineralocorticoid receptor antagonists

    NARCIS (Netherlands)

    Berg, T.N.A. van den; Rongen, G.A.P.J.M.; Frohlich, G.M.; Deinum, J.; Hausenloy, D.J.; Riksen, N.P.

    2014-01-01

    Despite state-of-the-art reperfusion therapy, morbidity and mortality remain significant in patients with an acute myocardial infarction. Therefore, novel strategies to limit myocardial ischemia-reperfusion injury are urgently needed. Mineralocorticoid receptor (MR) antagonists are attractive

  14. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.

    Science.gov (United States)

    Pepine, Carl J; Handberg, Eileen M; Cooper-DeHoff, Rhonda M; Marks, Ronald G; Kowey, Peter; Messerli, Franz H; Mancia, Giuseppe; Cangiano, José L; Garcia-Barreto, David; Keltai, Matyas; Erdine, Serap; Bristol, Heather A; Kolb, H Robert; Bakris, George L; Cohen, Jerome D; Parmley, William W

    2003-12-03

    Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant

  15. 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).

  16. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain.

    Science.gov (United States)

    Wermeling, Daniel P

    2005-08-01

    Ziconotide is a novel peptide that blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals. N-type calcium channels are present in the superficial laminae of the dorsal horn of the spinal cord. In various animal models of pain, intrathecal administration of ziconotide blocked nerve transmission and nociception. The United States Food and Drug Administration recently approved ziconotide intrathecal infusion for the management of severe chronic pain in patients who require intrathecal therapy and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine. The drug has a narrow therapeutic window and a lag time for the onset and offset of analgesia and adverse events. In early clinical trials, frequent and severe psychiatric and central nervous system adverse effects were associated with rapid intrathecal infusion (0.4 microg/hr) and frequent up-titration (every 12 hrs). Therefore, patients with psychiatric symptoms are not candidates for this drug. Drug trials of external intrathecal catheters and microinfusion devices demonstrated a 3% risk of meningitis. A low initial infusion rate of 0.1 microg/hour and limiting infusion rate increases to 2-3 times/week are now recommended. Patients responsive to intrathecal ziconotide require an implanted infusion system to receive long-term therapy.

  17. The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment.

    Science.gov (United States)

    Tamma, Grazia; Di Mise, Annarita; Ranieri, Marianna; Geller, Ari; Tamma, Roberto; Zallone, Alberta; Valenti, Giovanna

    2017-09-01

    Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney. In MDCK, tolvaptan prevented dDAVP-induced increase in ser256-AQP2 and osmotic water permeability. A similar effect on ser256-AQP2 was found in V1aR -/- mice, thus confirming the V2R selectively. Of note, calcium calibration in MDCK showed that tolvaptan per se caused calcium mobilization from the endoplasmic reticulum resulting in a significant increase in basal intracellular calcium. This effect was only observed in cells expressing the V2R, indicating that it requires the tolvaptan-V2R interaction. Consistent with this finding, tolvaptan partially reduced the increase in ser256-AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium-inhibitable AC type VI. Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Nuevas dihidropiridinas sintéticas con propiedades antagonistas del calcio vasoselectivas New synthetic dihydropyridines with vasoselective calcium antagonist properties

    Directory of Open Access Journals (Sweden)

    Loipa Galán Martínez

    2006-08-01

    Full Text Available Se estudiaron las propiedades antagonistas del calcio de 2 nuevas 1,4- dihidropiridinas sintéticas (I y II. Ambos compuestos disminuyeron en gran medida las contracciones de anillos de aorta de conejo y con menor potencia inhibieron las contracciones de papilares de ventrículo derecho de rata, acortaron la duración del potencial de acción cardíaco a 0 mV y redujeron la corriente de calcio tipo L en cardiomiocitos ventriculares aislados de rata. La inhibición de la corriente de calcio tipo L fue dependiente del potencial, con un incremento de la potencia de acción en más de un orden de magnitud de concentración en células parcialmente despolarizadas (-50 mV. Estos resultados permiten concluir que las 1,4- dihidropiridinas I y II poseen acciones antagonistas del calcio vasoselectivas marcadas y este mecanismo está dado por el bloqueo de la corriente de calcio tipo L de manera dependiente del potencialThe calcium antagonist properties of 2 new 1,4 synthetic dihydropyridines (I and II were studied. Both compounds reduced in a great extent the contractions of rabbit's aorta rings, and they inhibited with less potency the papillary contractions of rat's right ventricle. They also shortened the duration of the heart action potential to 0 mV, and decreased the L calcium current in ventricular cardiomyocites isolated from rats. The inhibition of calcium L current depended on the potential, with an increase of the action potential in more than one order of concentration magnitude in partially depolarized cells (-50 mV. These results allow to conclude that 1,4 dihydropyridines I and II have marked vasoselective calcium antagonist actions, and that this mechanism is due to the blockade of the calcium L current depending on the potential

  19. Synthesis and in Vtro Dual Calcium Channel Antagonist-Agonist Activity of some 1, 4-Dihydo-2,6-Dimethyl-3-Nitro and Cyano-4-(1-Methyl-5-Nitro-1H-Iimidazol-2-yl-5-Pyridinecarboxylates

    Directory of Open Access Journals (Sweden)

    A.R Mehdipour

    2008-09-01

    Full Text Available Background and purpose of the study: The vasorelaxant action of the dihydropyridines (DHPs provides many useful clinical indications. However, their negative effects on cardiac contractility is still of a great concern especially in patients with heart failure. Design and synthesis of dual action compounds, i. e. smooth muscle calcium channel antagonist/cardiac muscle calcium channel agonist provides better and safer compounds particularly in patients with compromised cardiac contractility. In the present study, dual cardioselective Ca2+ channel agonists / vascular selective smooth muscle Ca2+ channel antagonists as third generation of DHP drugs were synthesized by a reported method. Methods: Synthetic procedure involved condensation of isopropyl-3-aminocrotonate with nitroacetone and 1-methyl-5-nitroimidazole2-carboxaldehyde and condensation of alkylacetoacetates with 3-aminocrotonitryl and 1-methyl-5-nitro-1H-imidazole-2-carbaldehyde for the preparation of 1,4-Dihydo-2,6-dimethyl-3-nitro and cyano-4-(1-methyl-5-nitro-1H-imidazol-2-yl-5-pyridinecarboxylates, respectively. The in vitro effects of the synthesized compounds were evaluated on longitudal Smooth Muscle (GPILSM and Guinea Pig Left Atrium (GPLA preparations and finally, their conformations and structure-activity relationships were assessed.Results and major conclusion: All compounds showed calcium channel antagonist activity on isolated guinea pig ileum and some of them showed calcium channel agonist effects (or positive inotropic effect instead of calcium channel agonist effect on isolated guinea-pig left atrium. QSAR and conformational analyses showed that conformation and charge of aryl substituents at C4 position have a main role in antagonistic activity while carbonyl group at C5 position plays an important role in agonistic effects.

  20. [Does the diuretic effect of calcium inhibitors play an important role in the hypertensive efficacy?].

    Science.gov (United States)

    Maldonado Martin, A; Gil Extremera, B; Rubio Luengo, M A

    1995-04-08

    Calcium ions play an important role in the pathophysiology of hypertension. Calcium antagonists, a group of first line drugs in the treatment of hypertension, reduce the intracellular content of calcium in vascular smooth muscle cells, and decrease the peripheral vascular resistance and blood pressure. These drugs differ from other vasodilators in that they also have natriuretic effects; thus they can affect the kidney on three levels: Renal haemodynamics are affected by increased renal blood flow, and increased glomerular filtration rate. Changes in the renin-angiotensin system can decrease aldosterone secretion. Finally, they affect sodium management by acting directly on the renal tubule, increasing sodium excretion and inhibiting tubular reabsorption of this ion. The natriuretic effect of calcium antagonists is independent of the subject's sodium balance. The vasodilating action of these drugs is therefore accompanied by a natriuretic effect that makes satisfactory control of hypertension possible without placing the patient on a low-salt or salt-free diet.

  1. Isobolographic Analysis of Drug Combinations With Intrathecal BRL52537 (κ-Opioid Agonist), Pregabalin (Calcium Channel Modulator), AF 353 (P2X3 Receptor Antagonist), and A804598 (P2X7 Receptor Antagonist) in Neuropathic Rats.

    Science.gov (United States)

    Jung, Young-Hwan; Kim, Yeo Ok; Han, Jung Hyun; Kim, Yong-Chul; Yoon, Myung Ha

    2017-08-01

    Neuropathic pain should be treated with drug combinations exhibiting multiple analgesic mechanisms of action because the mechanism of neuropathic pain involves multiple physiological causes and is mediated by multiple pathways. In this study, we defined the pharmacological interaction of BRL52537 (κ-opioid agonist), pregabalin (calcium channel modulator), AF 353 (P2X3 receptor antagonist), and A804598 (P2X7 receptor antagonist). Animal models of neuropathic pain were established by spinal nerve ligation (SNL) in male Sprague-Dawley rats, and responses to the mechanical stimulation using von Frey filaments were measured. Drugs were administered by intrathecal route and were examined for antiallodynic effects, and drug interactions were evaluated using isobolographic analysis. The mRNA expression levels of pain-related receptors in each spinal cord or dorsal root ganglion of naïve, SNL, and drug-treated SNL rats were evaluated using real-time polymerase chain reaction. Intrathecal BRL52537, pregabalin, AF 353, and A804598 produced antiallodynic effects in SNL rats. In the drug combination studies, intrathecal coadministration of BRL52537 with pregabalin or A804598 exhibited synergistic interactions, and other drugs combinations showed additivity. The rank order of potency was observed as follows: BRL52537 + pregabalin > BRL52537 + A804598 > pregabalin + AF 353 > A804598 + pregabalin > BRL52537 + AF 353 > AF 353 + A804598. Real-time polymerase chain reaction indicated that alterations of P2X3 receptor and calcium channel mRNA expression levels were observed, while P2X7 receptor and κ-opioid receptor expression levels were not altered. These results demonstrated that intrathecal combination of BRL52537, pregabalin, AF 353, and A804598 synergistically or additively attenuated allodynia evoked by SNL, which suggests the possibility to improve the efficacy of single-drug administration.

  2. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    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 ...

  3. Effects of Suvorexant, a Dual Orexin/Hypocretin Receptor Antagonist, on Impulsive Behavior Associated with Cocaine.

    Science.gov (United States)

    Gentile, Taylor A; Simmons, Steven J; Watson, Mia N; Connelly, Krista L; Brailoiu, Eugen; Zhang, Yanan; Muschamp, John W

    2017-07-25

    Hypothalamic hypocretin (orexin) peptides mediate arousal, attention, and reward processing. Fibers containing orexins project to brain structures that govern motivated behavior, including the ventral tegmental area (VTA). A number of psychiatric conditions, including attention deficit hyperactivity disorder (ADHD) and substance use disorders, are characterized by deficits in impulse control, however the relationship between orexin and impulsive behavior is incompletely characterized. The effects of systemic or centrally administered orexin receptor (OXR) antagonists on measures of impulsive-like behavior in rats were evaluated using the five-choice serial reaction time task (5-CSRTT) and delay discounting procedures. These paradigms were also used to test the capacity of OXR antagonists to attenuate acute cocaine-evoked impulsivity. Finally, immunohistochemistry and calcium imaging were used to assess potential cellular mechanisms by which OXR blockade may influence motor impulsivity. Suvorexant, a dual (OX1/2R) orexin receptor antagonist, reduced cocaine-evoked premature responses in 5-CSRTT when administered systemically or directly into VTA. Neither suvorexant nor OX1R- or OX2R-selective compounds (SB334867 or TCS-OX2-29, respectively) altered delay discounting. Finally, suvorexant did not alter Fos-immunoreactivity within tyrosine hydroxylase-immunolabeled neurons of VTA, but did attenuate cocaine- and orexin-induced increases in calcium transient amplitude within neurons of VTA. Results from the present studies suggest potential therapeutic utility of OXR antagonists in reducing psychostimulant-induced motor impulsivity. These findings also support the view that orexin transmission is closely involved in executive function in normal and pathological conditions.Neuropsychopharmacology advance online publication, 16 August 2017; doi:10.1038/npp.2017.158.

  4. Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease

    NARCIS (Netherlands)

    Palmer, Andrew J; Annemans, Lieven; Roze, Stéphane; Lamotte, Mark; Lapuerta, Pablo; Chen, Roland; Gabriel, Sylvie; Carita, Paulo; Rodby, Roger A; de Zeeuw, Dick; Parving, Hans-Henrik

    OBJECTIVE: The aim of this study was to determine the most cost-effective time point for initiation of irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease. RESEARCH DESIGN AND METHODS: This study was a Markov model-simulated progression from microalbuminuria to overt

  5. 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.

  6. A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.

    Science.gov (United States)

    Cosman, F; Gilchrist, N; McClung, M; Foldes, J; de Villiers, T; Santora, A; Leung, A; Samanta, S; Heyden, N; McGinnis, J P; Rosenberg, E; Denker, A E

    2016-01-01

    In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis. This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P osteoporosis.

  7. Short term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate, and uric acid supersaturations

    Science.gov (United States)

    Cheungpasitporn, Wisit; Erickson, Stephen B.; Rule, Andrew D.; Enders, Felicity; Lieske, John C.

    2016-01-01

    Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events. PMID:26598423

  8. Effects of calcium antagonists on hypertension and diastolic function

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... Heart Research Unit and Cardiac Clinic, Department of. Medicine, University of Cape Town and ... diltiazem when give-n acutely to patients with hypertension is reported and the data compared with .... hypertrophic cardiomyopathy or aortic stenosis,6hypertrophic cardiomyopathy, and LV hypertrophy of ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Eltze, M.; Boer, R.; Sanders, K.H.; Boss, H.; Ulrich, W.R.; Flockerzi, D. (Byk Gulden Pharmaceuticals, Konstanz (Germany F.R.))

    1990-01-01

    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 (+)-({sup 3}H)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.

  10. 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.

  11. Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944.

    Science.gov (United States)

    Henbid, Mark T; Marks, Wendie N; Collins, Madeline J; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2017-10-01

    Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study was to examine the effects of the clinical stage pan-T-type calcium channel blocker, Z944, on sociability behaviour in male and female GAERS and non-epileptic control (NEC) animals. Female GAERS showed reduced sociability in a three-chamber sociability task whereas male GAERS, male NECs, and female NECs all showed a preference for the chamber containing a stranger rat. In drug trials, pre-treatment with 5mg/kg of Z944 normalized sociability in female GAERS. In contrast, female NECs showed impaired sociability following Z944 treatment. Dose-dependent decreases in locomotor activity were noted following Z944 treatment in both strains. Treatment with 10mg/kg of Z944 altered exploration such that only 8 of the 16 rats tested explored both sides of the testing chamber. In those that explored the chamber, significant preference for the stranger rat was observed in GAERS but not NECs. Overall, the data suggest that T-type calcium channels are critical in regulating sociability in both GAERS and NEC animals. Future research should focus on T-type calcium channels in the treatment of sociability deficits observed in disorders such as CAE. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kunert-Radek, J.; Stepien, H.; Lyson, K.; Pawlikowski, M.; Radek, A.

    1989-01-01

    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 (/sup 3/H)-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that varapamil (10/sup 4/-10/sup 5/M) and nimodipine (10/sup 4/-10/sup 6/M) significantly inhibited the (/sup 3/H)-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by stimultancous addition of calcium chloride (5x10/sup 3/M). 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.

  13. Pituitary sensitizing effect of GnRH antagonists: a mechanism explaining LH escape during IVF?

    NARCIS (Netherlands)

    Banga, F.R.; Huirne, J.A.F.; Korsen, T.; Homburg, R.R.; Hompes, P.G.A.; Lambalk, C.B.

    2010-01-01

    Background GnRH antagonists have been introduced to induce persistent LH suppression. Many studies show a gradual increase of LH levels after several days of GnRH antagonist administration, the so-called escape or rebound effect. We hypothesize that, under chronic GnRH antagonist administration, a

  14. The role of calcium in the effects of noradrenaline and phenoxybenzamine on adrenergic transmitter release from atria: no support for negative feedback of release

    OpenAIRE

    Kalsner, Stanley

    1981-01-01

    1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic α-adrenoceptors was investigated in guinea-pig atria previously incubated with [3H]-noradrenaline.

  15. Synthesis of two optically active calcium channel antagonists labelled with carbon-11 for in vivo cardiac PET imaging.

    Science.gov (United States)

    Dollé, F; Hinnen, F; Valette, H; Fuseau, C; Duval, R; Péglion, J L; Crouzel, C

    1997-04-01

    (+/-)-S11568 (1, 3-ethyl-5-methyl-(+/-)-2-[(2-(2-aminoethoxy)ethoxy) methyl]-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3, 5-dicarboxylate), has an in vitro profile of high potency and of high selectivity for the low-voltage dependent. L-type calcium channel. In in vitro binding studies, it displaced specifically bound (-)-[3H]PN 200-110 (isradipine (2), the reference molecule for in vitro studies) from cardiac and vascular smooth muscle preparations with potencies of 5.6 and 51 nM, respectively. It also appears as a pure pharmacological antagonist acting at a single channel L-type and free of any interaction at the benzothiazepine binding site such as amlodipine (3). Both enantiomers of S11568 have in vitro activities, the dextro isomer S12967 ((+)-1) being 6 to 18-fold less potent than the levo one S12968 ((-)-1). Two couples of optically active labelling precursors of S11568, ((-)-10/(+)-10 and (-)-14/(+)-14) have been synthesized using a modified Hantzsch's dihydropyridine synthesis. In both cases, the enantiomers were separated by preparative chiral HPLC. They both have been independently labelled with carbon-11, using [11C]diazomethane or [11C]iodomethane to give multimilliCurie quantities of (-)-1 (S12968) and (+)-1 (S12967) with high specific activities (500-1000 mCi/mumol, 18.5-37.0 GBq/mumol). Both enantiomers appear suitable for PET experiments: their myocardial concentration increases after a bolus injection to reach a maximum in 2 min and then remains on a plateau with a slight downslope while the blood concentration falls rapidly. Myocardial uptake was threefold higher than lung uptake, leading to a good contrast on PET images. The present preliminary biological results obtained in Beagle dogs showed that both enantiomers have similar myocardial kinetics and in vivo affinity for the left ventricular myocardium.

  16. Effects of TNF antagonists on immune and neuroendocrine system

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available In the article, the literature on the effects of TNFa-antagonists (etanercept, infliximab and adalimumab on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn’s disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo- pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

  17. Inhibition of vasoconstriction by AJ-2615, a novel calcium antagonist with alpha(1)-adrenergic receptor blocking activity in human conduit arteries used as bypass grafts.

    Science.gov (United States)

    Liu, M H; Floten, S H; Yang, Q; He, G W

    2001-09-01

    Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ-2615 and various vasoconstrictors was investigated in two ways. AJ-2615 caused complete relaxation in methoxamine-contracted IMA rings (100.0+/-0.0%; n = 8) and nearly full relaxation in potassium chloride-contracted IMA rings (91.4+/-5.7%; n = 8) or noradrenaline-contracted IMA rings (89.3+/-2.8%; n = 8). AJ-2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the alpha1-adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ-2615 (0.1-1 microM) significantly inhibited all the vasoconstrictor-mediated vasoconstriction except endothelin-1 in a concentration-dependent manner. The results suggested that in human IMA, AJ-2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and alpha1-adrenergic receptor blocking activity. AJ-2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm.

  18. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain.

    Science.gov (United States)

    Farkas, E; De Jong, G I; Apró, E; Keuker, J I; Luiten, P G

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen accumulation in the basement membrane of aging spontaneously hypertensive stroke-prone rats. The ratio of cortical capillaries with such vascular pathology occurred significantly more frequently in hypertensive animals. Nimodipine and nifedipine are potential drugs to decrease blood pressure in hypertension but their beneficial effects in experimental studies reach beyond the control of blood pressure. Nimodipine and nifedipine can alleviate ischemia-related symptoms and improve cognition. These drugs differ in that nifedipine, but not nimodipine reduces blood pressure at the here-used concentration while both drugs can penetrate the blood-brain barrier. Here we show that chronic treatment of aging hypertensive stroke-prone rats with nimodipine or nifedipine could preserve microvascular integrity in the cerebral cortex.

  19. Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

    Science.gov (United States)

    Krause, M; Keller, J; Beil, B; van Driel, I; Zustin, J; Barvencik, F; Schinke, T; Amling, M

    2015-03-01

    We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution

  20. Calcium

    Science.gov (United States)

    ... Turn to calcium-fortified (or "calcium-set") tofu, soy milk, tempeh, soy yogurt, and cooked soybeans (edamame). Calcium-fortified foods. Look for calcium-fortified orange juice, soy or rice milk, breads, and cereal. Beans. You can get decent ...

  1. Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists.

    Science.gov (United States)

    Sadek, Bassem; Kuder, Kamil; Subramanian, Dhanasekaran; Shafiullah, Mohamed; Stark, Holger; Lażewska, Dorota; Adem, Abdu; Kieć-Kononowicz, Katarzyna

    2014-06-01

    To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic drugs (AEDs), aromatic ether, and diether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in the maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in rats. The anticonvulsive effects of a systemic injection of 1-12 on MES-induced and PTZ-kindled seizures were evaluated against the reference AED phenytoin (PHT) and the structurally related H3R antagonist/inverse agonist pitolisant (PIT). Among the most promising ligands 2, 4, 5, and 11, there was a significant and dose-dependent reduction in the duration of tonic hind limb extension (THLE) in MES-induced seizure subsequent to administration of 4 and 5 [(5, 10, and 15 mg/kg, intraperitoneally (i.p.)]. The protective effects observed for the 1-(3-(3-(4-chlorophenyl)propoxy)propyl)-3-methylpiperidine derivative 11 at 10 mg/kg, i.p. were significantly greater than those of PIT, and were reversed by pretreatment with the central nervous system penetrant H1R antagonist pyrilamine (PYR) (10 mg/kg). Moreover, the protective action of the reference AED PHT, at a dose of 5 mg/kg (without considerable protection in the MES model), was significantly augmented when coadministered with derivative 11 (5 mg/kg, i.p.). Surprisingly, pretreatment with derivative 7 (10 mg/kg, i.p.), an ethylphenoxyhexyl-piperidine derivative without considerable protection in the MES model, potently altered PTZ-kindled seizure, significantly prolonged myoclonic latency time, and clearly shortened the total seizure time when compared with control, PHT, and PIT. These interesting results highlight the potential of H3R ligands as new AEDs or as adjuvants to available AED therapeutics.

  2. Effect of nutrient calcium on the cell wall composition and ...

    African Journals Online (AJOL)

    The effect of calcium in the nutrient medium on kikuyu grass (Pennisetum clandestinum Hochst), grown in a solution culture, was investigated. Calcium had no effect on the lignin content of leaf material, but decreased the lignin content per unit stem cell wall. Calcium appeared to have no significant effect on either the ...

  3. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  4. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    , in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-ylpropoxyphenylmethanol, and its (S-enantiomer (4 significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R-enantiomer (3 in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats. Keywords: histamine, H3 receptor, isomeric antagonists, anticonvulsant activity, stereo­selectivity

  5. The effect of farmyard manure and calcium ammonium nitrate ...

    African Journals Online (AJOL)

    The effect of farmyard manure and calcium ammonium nitrate fertilisers on micronutrient density (iron, zinc, manganese, calcium and potassium) and seed yields of solanium villosum (black nightshade) and cleome gynandra (cat whiskers) on uetric nitisol.

  6. Inhibition of vasoconstriction by AJ-2615, a novel calcium antagonist with α1-adrenergic receptor blocking activity in human conduit arteries used as bypass grafts

    Science.gov (United States)

    Liu, Ming-Hui; Floten, Storm H; Yang, Qin; He, Guo-Wei

    2001-01-01

    Aims Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). Methods We studied 264 IMA rings taken from 65 patients undergoing coronary artery bypass grafting surgery with organ bath technique. The interaction between AJ-2615 and various vasoconstrictors was investigated in two ways. Results AJ-2615 caused complete relaxation in methoxamine-contracted IMA rings (100.0±0.0%; n = 8) and nearly full relaxation in potassium chloride-contracted IMA rings (91.4±5.7%; n = 8) or noradrenaline-contracted IMA rings (89.3±2.8%; n = 8). AJ-2615 also induced remarkable relaxation in IMA rings contracted by other vasoconstrictors. In comparison with the α1-adrenoceptor antagonist prazosin, AJ 2615 showed similar maximal relaxation in IMA rings contracted by methoxamine or norepinephrine. On the other hand, incubation with AJ-2615 (0.1–1 µm) significantly inhibited all the vasoconstrictor-mediated vasoconstriction except endothelin-1 in a concentration-dependent manner. Conclusions The results suggested that in human IMA, AJ-2615 has an inhibitory effect on vasoconstriction mediated by a variety of vasoconstrictors and the mechanism of relaxation may be related to its calcium antagonism and α1-adrenergic receptor blocking activity. AJ-2615 may have important clinical implications for patients undergoing coronary artery bypass surgery for reversing and preventing graft spasm. PMID:11560560

  7. [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. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  8. 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.

  9. Induction of enhanced postnatal expression of immunoreactive calbindin-D28k in rat forebrain by the calcium antagonist nimodipine

    NARCIS (Netherlands)

    Luiten, Paul G.M.; Buwalda, Bauke; Traber, Jörg; Nyakas, Csaba

    1994-01-01

    The early postnatal development of immunoreactive calbindin-D28k (CaB-ir) containing neuronal systems in hippocampus and parietal cortex was studied in offspring of Wistar rats chronically treated with either the Ca2+-channel antagonist nimodipine or placebo food. The drug was applied to the mother

  10. Evaluating the function of calcium antagonist on the Cd-induced stress in sperm of Russian sturgeon, Acipenser gueldenstaedtii

    Energy Technology Data Exchange (ETDEWEB)

    Li Zhihua, E-mail: zhihuali06@yahoo.com [University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany (Czech Republic); Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Jingzhou 434000 (China); Li Ping [University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany (Czech Republic); Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Jingzhou 434000 (China); Rodina, Marek; Randak, Tomas [University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany (Czech Republic)

    2010-11-15

    In the current study, the sperm of Russian sturgeon (Acipenser gueldenstaedtii) was used to evaluate the roles of Verapamil (VRP), a calcium channel blocker, against cadmium (Cd)-induced stress. Sturgeon sperm were exposed for 2 h at 50 {mu}g/L VRP, 5.0 {mu}g/L Cd, the mixture of 50 {mu}g/L VRP + 5.0 {mu}g/L Cd, 50 {mu}g/L Cd and the mixture of 50 {mu}g/L VRP + 50 {mu}g/L Cd. After exposure, the sperm motility parameters (motility and velocity), oxidative stress levels (lipid peroxidation [LPO] and carbonyl protein [CP]) and antioxidant enzyme activities (superoxide dismutase [SOD], glutathione reductase [GR], glutathione peroxidase [GPx]) were measured in sturgeon sperm. Compared to the control, Cd-induced stress was apparent as reflected by depressed motility parameters, induced oxidative stress and inhibited antioxidant enzyme activities at both Cd concentrations. In the presence of VRP, Cd-induced stress was reduced in sturgeon sperm, especially all the measured parameters in the sperm exposed at 5.0 {mu}g/L Cd returned to control levels, expect for the sperm motility. The present results indicate that VRP can reduce the Cd-induced stress in sturgeon sperm and suggest that using of sperm in vitro assays may provide a novel and efficient means for evaluating the effects of residual metals in the aquatic environment of sturgeon.

  11. Evaluating the function of calcium antagonist on the Cd-induced stress in sperm of Russian sturgeon, Acipenser gueldenstaedtii.

    Science.gov (United States)

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

    2010-11-15

    In the current study, the sperm of Russian sturgeon (Acipenser gueldenstaedtii) was used to evaluate the roles of Verapamil (VRP), a calcium channel blocker, against cadmium (Cd)-induced stress. Sturgeon sperm were exposed for 2h at 50μg/L VRP, 5.0μg/L Cd, the mixture of 50μg/L VRP+5.0μg/L Cd, 50μg/L Cd and the mixture of 50μg/L VRP+50μg/L Cd. After exposure, the sperm motility parameters (motility and velocity), oxidative stress levels (lipid peroxidation [LPO] and carbonyl protein [CP]) and antioxidant enzyme activities (superoxide dismutase [SOD], glutathione reductase [GR], glutathione peroxidase [GPx]) were measured in sturgeon sperm. Compared to the control, Cd-induced stress was apparent as reflected by depressed motility parameters, induced oxidative stress and inhibited antioxidant enzyme activities at both Cd concentrations. In the presence of VRP, Cd-induced stress was reduced in sturgeon sperm, especially all the measured parameters in the sperm exposed at 5.0μg/L Cd returned to control levels, expect for the sperm motility. The present results indicate that VRP can reduce the Cd-induced stress in sturgeon sperm and suggest that using of sperm in vitro assays may provide a novel and efficient means for evaluating the effects of residual metals in the aquatic environment of sturgeon. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. 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.

  13. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    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.

  14. Calcium

    Science.gov (United States)

    ... and blood vessels contract and expand, to secrete hormones and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with ...

  15. 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.

  16. Effects of physical variables on settling velocities of calcium and ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Effects of physical variables on settling velocities of calcium and strontium phosphates ... Department of Chemistry, Rivers State University of Science & Technology, Port Harcourt, Nigeria .... simplified stoichiometric chemical reactions.

  17. Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids

    Science.gov (United States)

    Bandyopadhyay, Arpan; O'Brien, Sofie; Frank, Kristi L.; Dunny, Gary M.

    2016-01-01

    ABSTRACT Enterococcus faecalis, a common causative agent of hospital-acquired infections, is resistant to many known antibiotics. Its ability to acquire and transfer resistance genes and virulence determinants through conjugative plasmids poses a serious concern for public health. In some cases, induction of transfer of E. faecalis plasmids results from peptide pheromones produced by plasmid-free recipient cells, which are sensed by the plasmid-bearing donor cells. These plasmids generally encode an inhibitory peptide that competes with the pheromone and suppresses self-induction of donors. We recently demonstrated that the inhibitor peptide encoded on plasmid pCF10 is part of a unique quorum-sensing system in which it functions as a “self-sensing signal,” reducing the response to the pheromone in a density-dependent fashion. Based on the similarities between regulatory features controlling conjugation in pAD1 and pAM373 and those controlling conjugation in pCF10, we hypothesized that these plasmids are likely to exhibit similar quorum-sensing behaviors. Experimental findings indicate that for both pAD1 and pAM373, high donor densities indeed resulted in decreased induction of the conjugation operon and reduced conjugation frequencies. This effect was restored by the addition of exogenous inhibitor, confirming that the inhibitor serves as an indicator for donor density. Donor density also affects cross-species conjugative plasmid transfer. Based on our experimental results, we propose models for induction and shutdown of the conjugation operon in pAD1 and pAM373. IMPORTANCE Enterococcus faecalis is a leading cause of hospital-acquired infections. Its ability to transfer antibiotic resistance and virulence determinants by sharing its genetic material with other bacteria through direct cell-cell contact via conjugation poses a serious threat. Two antagonistic signaling peptides control the transfer of plasmids pAD1 and pAM373: a peptide pheromone produced by

  18. Calcium

    Science.gov (United States)

    ... from dietary supplements are linked to a greater risk of kidney stones, especially among older adults. But calcium from foods does not appear to cause kidney stones. For most people, other factors (such as not drinking enough fluids) probably have ...

  19. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

    Science.gov (United States)

    Karp, Heini J; Ketola, Maarit E; Lamberg-Allardt, Christel J E

    2009-11-01

    Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

  20. Acute Effects of Antagonist Stretching on Jump Height and Knee Extension Peak Torque

    OpenAIRE

    Sandberg, John B.

    2012-01-01

    A great deal of research has shown decrements in force and power following static stretching. There has been little research investigating the acute effects of static stretching of the antagonist on the expression of strength and power. The purpose of this study was to investigate the effects of static stretching of the antagonist muscles on a variety of strength and power measures. Sixteen active males were tested for vertical jump height and isokinetic torque production in a slow knee exten...

  1. Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure.

    Science.gov (United States)

    Gonsai, N H; Amin, V H; Mendpara, C G; Speth, R; Hale, G M

    2017-11-08

    Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist. A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion. All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors. Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs. © 2017 John Wiley & Sons Ltd.

  2. Effects of extracellular calcium on calcium transport during hyperthermia of tumor cells.

    Science.gov (United States)

    Anghileri, L J; Marcha, C; Crone-Escanyé, M C; Robert, J

    1985-08-01

    The effects of different concentrations of extracellular ion calcium on the transport of calcium by tumor cells have been studied by means of the uptake of radiocalcium. Tumor cells incubated at 45 degrees C take up 4-10 times the amount of radioactivity incorporated by cells incubated at 37 degrees C. The difference is still greater (up to 100 times) for the intracellular incorporation as assessed by elimination of the membrane-bound calcium by EGTA treatment. The possible mechanisms involved in this differential behavior are discussed.

  3. 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.

  4. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    DEFF Research Database (Denmark)

    Brygger, Louise; Herrstedt, Jørn

    2014-01-01

    INTRODUCTION: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients. AREAS COVERED: The purpose of this article is to outline the risk of cardiac adverse events......, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV....

  5. Effect of beta-adrenergic receptor antagonists on nicotine-induced tail-tremor in rats.

    Science.gov (United States)

    Suemaru, K; Gomita, Y; Furuno, K; Araki, Y

    1993-09-01

    The effects of various beta-adrenergic receptor antagonists on nicotine-induced tail-tremor were investigated in rats. Atenolol (5 and 10 mg/kg, IP), arotinolol (5 and 10 mg/kg, IP), and carteolol (5 and 10 mg/kg, IP), hydrophilic beta-adrenergic receptor antagonists, did not affect the tail-tremor induced by nicotine given at a dose of 0.5 mg/kg SC. However, propranolol (5-20 mg/kg, IP) and pindolol (5-20 mg/kg, IP), nonselective and lipophilic beta-adrenergic receptor antagonists, did suppress the tail-tremor dose dependently. In contrast, metoprolol (5-20 mg/kg, IP), lipophilic and beta 1-selective adrenergic receptor antagonists, did not show such an effect. These results suggest that nicotine-induced tail-tremors may be mediated through central beta 2-adrenergic receptors as an appearance and developmental mechanism.

  6. EFFECTS OF PRETREATMENTS ON CALCIUM ACCUMULATION ONTO GAC

    OpenAIRE

    Miño, Esteban R.; Okuda, Tetsuji; NISHIJIMA, Wataru; OKADA, Mitsumasa

    2007-01-01

    The effect of coagulation and ozonation as pretreatments for granular activated carbon (GAC) filtration on calcium accumulation onto GAC was studied. Three kinds of FA solutions extracted from commercial leaf mold for horticulture were used: FA itself, FA after coagulation (FA-c) and FA after ozonation (FA-oz). Coagulation used as pretreatment before GAC filtration significantly decreased calcium accumulation onto GAC while ozonation caused a small increase on calcium accumulation onto GA...

  7. The effect of calcium on auxin depletion-induced tomato ...

    African Journals Online (AJOL)

    Indole-3-acetic acid (IAA) and calcium are the most important factors that instigate plant organ abscission. This study aimed to elucidate the mechanisms that underlie the effects of IAA and calcium on delayed abscission in tomato. The results showed a clear trend towards reduced abscission rates with increased ...

  8. The effect of buffered calcium diffusion on neurotransmitter release

    Science.gov (United States)

    Ponce Dawson, Silvina; Uchitel, Osvaldo D.

    2002-08-01

    Calcium plays a major role in inter-neuron communication. It has recently been observed that the scaling relationship between extracellular calcium concentration and postsynaptic response is different depending on the channel through which calcium enters the presynaptic neuron. Experiments suggest that the two types of calcium channels probed in this regard are at different mean distances from the neurotransmitter-containing vesicles. In this work we investigate whether the effect of calcium buffers along the path from the channel to the vesicle sensor can be responsible for the differences observed. Our results show that buffers cannot account for this change. This study also allows us to probe the limitations of the rapid buffering approximation in the presence of strong and localized sources.

  9. Effects of combining opioids and clinically available NMDA receptor antagonists in the treatment of pain

    NARCIS (Netherlands)

    Snijdelaar, D.G.

    2005-01-01

    This thesis concerns the effects of combining opioids with clinically available NMDA receptor antagonists in the treatment of acute and chronic pain. There are a number of problems with the use of opioids, such as, the development of tolerance/hyperalgesia, the reduced effectiveness in (central)

  10. Modulation of L-type calcium channels by sodium ions.

    OpenAIRE

    Balke, C W; Wier, W G

    1992-01-01

    It is universally believed that the removal of external sodium ions is without effect on calcium current. We now report that in enzymatically isolated guinea pig ventricular cells, the replacement of external sodium ions with certain other cations causes a 3- to 6-fold increase in peak L-type calcium current. The increase in current is reversibly blocked by L-type calcium-channel antagonists, not mediated by changes in internal calcium, and is inhibited by intracellular 5'-adenylyl imidodipho...

  11. Effects of external calcium on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7.

    Science.gov (United States)

    Ye, Li; Zhang, Chunyan; Li, Jiyang; Shi, Xunlong; Feng, Meiqing

    2012-03-01

    Calcium is a known signalling molecule in eukaryotic cells and plays a central role in the regulation of many cellular processes. In the following study, we report on the effect of external calcium treatments on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7. We observed that the intracellular calcium content of P. bainier 229-7 mycelia was increased in response to exposure to high external Ca(2+) concentrations. Both ginsenoside Rd biotransformation and β-glucosidase activity were both found to be dependent on the external calcium concentration. At an optimal Ca(2+) concentration of 45 mM, maximal ginsenoside Rd bioconversion rate of 92.44% was observed and maximal β-glucosidase activity of 0.1778 U was reached in a 72-h biotransformation. The Ca(2+) channel blocker Verapamil blocked the trans-membrane influx of calcium and decreased ginsenoside Rd biotransformatiom. In addition, β-glucosidase activity and ginsenoside Rd content decreased by 36.0 and 29.2% respectively after a 72-h incubation in the presence of 0.05 mM Calmodulin (CaM) antagonist Perphenazine. These results suggest that both Ca(2+) channels and CaM are involved in ginsenoside Rd biotransformation via regulation of β-glucosidase activity. This is the first report regarding the effects of calcium signal transduction on biotransformation and enzyme activity in fungi.

  12. Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

    Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

  13. Effects of α-adrenoceptor antagonists on ABCG2/BCRP-mediated resistance and transport.

    Science.gov (United States)

    Takara, Kohji; Yamamoto, Kazuhiro; Matsubara, Mika; Minegaki, Tetsuya; Takahashi, Minoru; Yokoyama, Teruyoshi; Okumura, Katsuhiko

    2012-01-01

    Acquired resistance of cancer cells to various chemotherapeutic agents is known as multidrug resistance, and remains a critical factor in the success of cancer treatment. It is necessary to develop the inhibitors for multidrug resistance. The aim of this study was to examine the effects of eight α-adrenoceptor antagonists on ABCG2/BCRP-mediated resistance and transport. Previously established HeLa/SN100 cells, which overexpress ABCG2/BCRP but not ABCB1/MDR1, were used. The effects of the antagonists on sensitivity to mitoxantrone and the transport activity of Hoehst33342, both substrates for ABCG2/BCRP, were evaluated using the WST-1 assay and cellular kinetics, respectively. ABCG2/BCRP mRNA expression and the cell cycle were also examined by real-time RT-PCR and flow cytometry, respectively. Sensitivity to mitoxantrone was reversed by the α-adrenoceptor antagonists in a concentration-dependent manner, although such effects were also found in the parental HeLa cells. Levels of ABCG2/BCRP mRNA expression were not influenced by the antagonists. The transport activity of Hoechst33342 was decreased by doxazosin and prazosin, but unaffected by the other antagonists. In addition, doxazosin and prazosin increased the proportion of S phase cells in the cultures treated with mitoxantrone, whereas the other α-adrenoceptor antagonists increased the percentage of cells in G(2)/M phase. These findings suggested that doxazosin and prazosin reversed resistance mainly by inhibiting ABCG2/BCRP-mediated transport, but the others affected sensitivity to mitoxantrone via a different mechanism.

  14. Effects of α-adrenoceptor antagonists on ABCG2/BCRP-mediated resistance and transport.

    Directory of Open Access Journals (Sweden)

    Kohji Takara

    Full Text Available Acquired resistance of cancer cells to various chemotherapeutic agents is known as multidrug resistance, and remains a critical factor in the success of cancer treatment. It is necessary to develop the inhibitors for multidrug resistance. The aim of this study was to examine the effects of eight α-adrenoceptor antagonists on ABCG2/BCRP-mediated resistance and transport. Previously established HeLa/SN100 cells, which overexpress ABCG2/BCRP but not ABCB1/MDR1, were used. The effects of the antagonists on sensitivity to mitoxantrone and the transport activity of Hoehst33342, both substrates for ABCG2/BCRP, were evaluated using the WST-1 assay and cellular kinetics, respectively. ABCG2/BCRP mRNA expression and the cell cycle were also examined by real-time RT-PCR and flow cytometry, respectively. Sensitivity to mitoxantrone was reversed by the α-adrenoceptor antagonists in a concentration-dependent manner, although such effects were also found in the parental HeLa cells. Levels of ABCG2/BCRP mRNA expression were not influenced by the antagonists. The transport activity of Hoechst33342 was decreased by doxazosin and prazosin, but unaffected by the other antagonists. In addition, doxazosin and prazosin increased the proportion of S phase cells in the cultures treated with mitoxantrone, whereas the other α-adrenoceptor antagonists increased the percentage of cells in G(2/M phase. These findings suggested that doxazosin and prazosin reversed resistance mainly by inhibiting ABCG2/BCRP-mediated transport, but the others affected sensitivity to mitoxantrone via a different mechanism.

  15. Effect of Ultrasound on Calcium Carbonate Crystallization

    NARCIS (Netherlands)

    Wagterveld, R.M.

    2013-01-01

    Scaling comprises the formation of hard mineral deposits on process or membrane equipment and calcium carbonate is the most common scaling salt. Especially in reverse osmosis (RO) membrane systems, scale formation has always been a serious limitation, causing flux decline, membrane degradation, loss

  16. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease

    DEFF Research Database (Denmark)

    Currie, Gemma; Taylor, Alison H M; Fujita, Toshiro

    2016-01-01

    BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia...... is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. METHODS: We conducted a meta......-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators...

  17. Development of NMDAR antagonists with reduced neurotoxic side effects: a study on GK11.

    Directory of Open Access Journals (Sweden)

    Delphine Vandame

    Full Text Available The NMDAR glutamate receptor subtype mediates various vital physiological neuronal functions. However, its excessive activation contributes to neuronal damage in a large variety of acute and chronic neurological disorders. NMDAR antagonists thus represent promising therapeutic tools that can counteract NMDARs' overactivation. Channel blockers are of special interest since they are use-dependent, thus being more potent at continuously activated NMDARs, as may be the case in pathological conditions. Nevertheless, it has been established that NMDAR antagonists, such as MK801, also have unacceptable neurotoxic effects. Presently only Memantine is considered a safe NMDAR antagonist and is used clinically. It has recently been speculated that antagonists that preferentially target extrasynaptic NMDARs would be less toxic. We previously demonstrated that the phencyclidine derivative GK11 preferentially inhibits extrasynaptic NMDARs. We thus anticipated that this compound would be safer than other known NMDAR antagonists. In this study we used whole-genome profiling of the rat cingulate cortex, a brain area that is particularly sensitive to NMDAR antagonists, to compare the potential adverse effects of GK11 and MK801. Our results showed that in contrast to GK11, the transcriptional profile of MK801 is characterized by a significant upregulation of inflammatory and stress-response genes, consistent with its high neurotoxicity. In addition, behavioural and immunohistochemical analyses confirmed marked inflammatory reactions (including astrogliosis and microglial activation in MK801-treated, but not GK11-treated rats. Interestingly, we also showed that GK11 elicited less inflammation and neuronal damage, even when compared to Memantine, which like GK11, preferentially inhibits extrasynaptic NMDAR. As a whole, our study suggests that GK11 may be a more attractive therapeutic alternative in the treatment of CNS disorders characterized by the overactivation

  18. Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension

    NARCIS (Netherlands)

    P.J.J. Admiraal (Peter Jan Jacobus); J.A.M.J.L. Janssen (Joseph); J.M. Kroodsma; W.A. de Ronde (Willem); F. Boomsma (Frans); J. Sissmann; P.J. Blankestijn (Peter); P.G.H. Mulder (Paul); A.J. Man in 't Veld (Arie); A.H. van den Meiracker (Anton)

    1995-01-01

    textabstractWe studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial,

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

    NARCIS (Netherlands)

    Vogt, Liffert; Chiurchiu, Carlos; Chadha-Boreham, Harbajan; Danaietash, Parisa; Dingemanse, Jasper; Hadjadj, Samy; Krum, Henry; Navis, Gerjan; Neuhart, Eric; Parvanova, Aneliya I.; Ruggenenti, Piero; Woittiez, Arend Jan; Zimlichman, Reuven; Remuzzi, Giuseppe; de Zeeuw, Dick

    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

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

    NARCIS (Netherlands)

    Vogt, Liffert; Chiurchiu, Carlos; Chadha-Boreham, Harbajan; Danaietash, Parisa; Dingemanse, Jasper; Hadjadj, Samy; Krum, Henry; Navis, Gerjan; Neuhart, Eric; Parvanova, Aneliya I.; Ruggenenti, Piero; Woittiez, Arend Jan; Zimlichman, Reuven; Remuzzi, Giuseppe; de Zeeuw, Dick

    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

  1. 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

  2. Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

    NARCIS (Netherlands)

    L. Edvinsson (Lars); K.Y. Chan (Kayi); S. Eftekhari; E. Nilsson (Elisabeth); R. de Vries (René); H. Säveland (Hans); C.M.F. Dirven (Clemens); A.H.J. Danser (Jan)

    2010-01-01

    textabstractIntroduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on

  3. antagonistic effect of native bacillus isolates against black root rot of ...

    African Journals Online (AJOL)

    ACSS

    objective of this study was to evaluate the biological control ability of native Bacillus species on the basis of their antagonistic effects against F. ... isolates significantly (P<0.05) reduced radial mycelial growth of the pathogen. Seven bacterial isolates ..... in the biological control of plant pathogens (Asaka and Shoda, 1996;.

  4. The effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate bone cement

    Science.gov (United States)

    Razali, N. N.; Sukardi, M. A.; Sopyan, I.; Mel, M.; Salleh, H. M.; Rahman, M. M.

    2018-01-01

    The objective of this study is to determine the effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate cement (CPC) for bone filling applications. Hydroxyapatite powder was synthesized via hydrothermal method using calcium oxide, CaO and ammonium dihydrogen phosphate, NH4H2PO4 as the calcium and phosphorus precursors respectively. The effects of calcium excess were evaluated by varying the CaO content at 0, 5 and 15 mole %. The precursors were then refluxed in distilled water at 90-100°C and dried overnight until the calcium phosphate powder was formed. CPC was then produced by mixing the synthesized powder with distilled water at the powder-to-liquid (P/L) ratio of 1.5. The result from the morphological properties of CPC shows the increase in agglomeration and particles size with 5 mole % of calcium excess but decreased with 15 mole % of calcium excess in CPC. This result was in agreement with the compressive strength result where the CPC increased its strength with 5 mole % of calcium excess but reduced with 15 mole % of calcium excess. The excess in calcium precursor also significantly improved the setting time but reduced the injectability of CPC.

  5. Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis.

    Science.gov (United States)

    Qiao, Hui; Li, Yun; Xu, Zhendong; Li, Wenxian; Fu, Zhijian; Wang, Yuezhi; King, Alexander; Wei, Huafeng

    2017-09-01

    In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. The dose-response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol's effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.

  6. ACET is a highly potent and specific kainate receptor antagonist: Characterisation and effects on hippocampal mossy fibre function

    Science.gov (United States)

    Dargan, Sheila L.; Clarke, Vernon R. J.; Alushin, Gregory M.; Sherwood, John L.; Nisticò, Robert; Bortolotto, Zuner A.; Ogden, Ann M.; Bleakman, David; Doherty, Andrew J.; Lodge, David; Mayer, Mark L.; Fitzjohn, Stephen M.; Jane, David E.; Collingridge, Graham L.

    2009-01-01

    Kainate receptors (KARs) are involved in both NMDA receptor-independent long-term potentiation (LTP) and synaptic facilitation at mossy fibre synapses in the CA3 region of the hippocampus. However, the identity of the KAR subtypes involved remains controversial. Here we used a highly potent and selective GluK1 (formerly GluR5) antagonist (ACET) to elucidate roles of GluK1-containing KARs in these synaptic processes. We confirmed that ACET is an extremely potent GluK1 antagonist, with a Kb value of 1.4 ± 0.2 nM. In contrast, ACET was ineffective at GluK2 (formerly GluR6) receptors at all concentrations tested (up to 100 μM) and had no effect at GluK3 (formerly GluR7) when tested at 1 μM. The X-ray crystal structure of ACET bound to the ligand binding core of GluK1 was similar to the UBP310-GluK1 complex. In the CA1 region of hippocampal slices, ACET was effective at blocking the depression of both fEPSPs and monosynaptically-evoked GABAergic transmission induced by ATPA, a GluK1 selective agonist. In the CA3 region of the hippocampus, ACET blocked the induction of NMDA receptor-independent mossy fibre LTP. To directly investigate the role of pre-synaptic GluK1-containing KARs we combined patch-clamp electrophysiology and 2-photon microscopy to image Ca2+ dynamics in individual giant mossy fibre boutons. ACET consistently reduced short-term facilitation of pre-synaptic calcium transients induced by 5 action potentials evoked at 20-25 Hz. Taken together our data provide further evidence for a physiological role of GluK1-containing KARs in synaptic facilitation and LTP induction at mossy fibre-CA3 synapses. PMID:18789344

  7. New approaches to the management of peripheral vertigo: efficacy and safety of two calcium antagonists in a 12-week, multinational, double-blind study.

    Science.gov (United States)

    Pianese, Carlo Pane; Hidalgo, Lourdes Olivia Vales; González, Ramón Hinojosa; Madrid, Cecilia Esteinou; Ponce, Jorge Enrique Cruz; Ramírez, Alberto Mañé; Morán, Luis Martínez; Arenas, José Enrique Poó; Rubio, Arturo Torres y Gutiérrez; Uribe, Jorge Olguin; Abiuso, José; Hanuch, Enrique; Alegría, Juan; Volpi, Claudio; Flaskamp, Renate; Sanjuán, Augusto Peñaranda; Gómez, Juan Manuel García; Hernández, Jaime; Pedraza, Alvaro; Quijano, Diana; Martínez, Carolina; Castañeda, Juan Ramón; Guerra, Oscar Jorge Cardeñosa; F, G Valencia

    2002-05-01

    To evaluate the efficacy and safety profile of one 30-mg nimodipine oral tablet taken three times per day (one tablet with breakfast, one with lunch, and one with dinner) or one 150-mg cinnarizine verum oral capsule taken once each day with dinner for 12 weeks. Comparative in a double-blind, multinational pilot study. Tertiary referral center. A total of 221 patients met the study criteria; of that total, 181 adult patients completed the study, including 135 women and 46 men whose ages ranged from 20 to 80 years. Two calcium antagonists were used to treat vertigo (nimodipine, 89 patients; cinnarizine, 92 patients), and all patients were maintained on the same dosage regimen until they completed 12 weeks of treatment. Patients were evaluated at 2-and 4-week intervals; an additional evaluation was made at Week 14 to determine vertigo recurrence in the posttreatment period. The response was evaluated by using the vertigo severity index, a count of vertigo episodes in a given time period. Each episode is weighted according to its intensity. Nimodipine treatment decreased the incidence of moderate vertigo episodes by 78.8% and decreased severe vertigo episodes by 85.0%. Cinnarizine treatment decreased the incidence of moderate vertigo episodes by 65.8% and decreased severe vertigo episodes by 89.8%. Nimodipine and cinnarizine exhibited similar safety profiles. Only two patients withdrew from the study because of adverse events possibly related to the study drug. One patient withdrew from the cinnarizine group because of headache, and one patient withdrew from the nimodipine group because of lipothymia. These data confirm the marked efficacy of both nimodipine and cinnarizine in the treatment of vestibular vertigo.

  8. Prevention of calcium-induced membrane structural alterations in erythrocyte membranes by flunarizine

    NARCIS (Netherlands)

    Thomas, Peter G.; Zimmermann, A.G.; Verkleij, A.J.

    1988-01-01

    The calcium antagonist flunarizine is shown to be able to prevent particle aggregation, membrane aggregation and blebbing resulting from elevated calcium concentrations. The anti-ischemic effects of flunarizine may therefore result in part from its ability to directly interfere with calcium-membrane

  9. Antagonistic effect of brevicin on Gram positive and Gram negative ...

    African Journals Online (AJOL)

    A new low molecular weight brevicin produced by Lactobacillus brevis NS01 has greater antimicrobial activity on Gram positive and negative food borne bacteria. This is stable at high temperature acidic to neutral pH, non proteolytic enzymes and organic solvents. The synergistic effect of brevicin with ...

  10. 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.

  11. Effects of Olopatadine Hydrochloride, a Histamine H 1 Receptor Antagonist, on Histamine-Induced Skin Responses

    OpenAIRE

    Takashi Hashimoto; Norito Ishii; Takahiro Hamada; Teruki Dainichi; Tadashi Karashima; Takekuni Nakama; Shinichiro Yasumoto

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. Th...

  12. Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses.

    Science.gov (United States)

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H(1) receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration.

  13. Effects of Olopatadine Hydrochloride, a Histamine H1 Receptor Antagonist, on Histamine-Induced Skin Responses

    Science.gov (United States)

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration. PMID:20886023

  14. Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists

    Science.gov (United States)

    Greineisen, William E.; Turner., Helen

    2013-01-01

    The active constituents of Cannabis sativa have been used for centuries as recreational drugs and medicinal agents. Today, marijuana is the most prevalent drug of abuse in the United States and, conversely, therapeutic use of marijuana constituents are gaining mainstream clinical and political acceptance. Given the documented contributions of endocannabinoid signaling to a range of physiological systems, including cognitive function, and the control of eating behaviors, it is unsurprising that cannabinoid receptor agonists and antagonists are showing significant clinical potential. In addition to the neuroactive effects of cannabinoids, an emerging body of data suggests that both endogenous and exogenous cannabinoids are potently immunoactive. The central premise of this review article is that the immunological effects of cannabinoids should be considered in the context of each prescribing decision. We present evidence that the immunological effects of cannabinoid receptor agonists and antagonists are highly relevant to the spectrum of disorders for which cannabinoid therapeutics are currently offered. PMID:20219697

  15. Effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, on urinary excretions of various electrolytes in rats.

    Science.gov (United States)

    Nagashima, K; Karasawa, A

    1996-07-01

    We examined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, on urine volume and urinary excretions of various electrolytes in saline-loaded rats, as compared with those of furosemide, trichlormethiazide (TCM), acetazolamide and amiloride. KW-3902 at doses of 0.001-1 mg/kg (p.o.) significantly increased urine volume and excretions of sodium, calcium, magnesium, chloride and bicarbonate. In addition, KW-3902 shifted urine pH to alkaline and decreased free water reabsorption. KW-3902 did not induce kaliuresis, whereas furosemide (30 mg/kg, p.o.), TCM (1 mg/kg, p.o.) and acetazolamide (25 mg/kg, p.o.) induced kaliuresis. In the KW-3902-treated group, the increases in bicarbonate excretion and urine pH were less prominent than those induced by acetazolamide, and the excretions of sodium, calcium, magnesium and chloride were similar to those induced by furosemide. The present results suggest that the adenosine A1-receptor antagonist exhibits diuresis by the inhibited reabsorption of electrolytes, not only at the proximal tubule but also at the distal tubule.

  16. The Effect of Coasting on Intracytoplasmic Sperm Injection Outcome in Antagonist and Agonist Cycle

    Directory of Open Access Journals (Sweden)

    İltemir Duvan Z.Candan,

    2017-01-01

    Full Text Available Background Coasting can reduce the ovarian hyperstimulation syndrome (OHSS risk in ovulation induction cycles before intracytoplasmic sperm injection (ICSI. This study aimed to investigate the effect of gonadotropin-releasing hormone (GnRH agonist and GnRH antagonist protocols to controlled ovarian hyperstimulation (COH cycles with coasting on the parameters of ICSI cycles and the outcome. Materials and Methods In a retrospective cohort study, 117 ICSI cycles were per- formed and coasting was applied due to hyperresponse, between 2006 and 2011. The ICSI outcomes after coasting were then compared between the GnRH agonist group (n=91 and the GnRH antagonist group (n=26. Results The duration of induction and the total consumption of gonadotropins were found to be similar. Estradiol (E2 levels on human chorionic gonadotropin (hCG day were found higher in the agonist group. Coasting days were similar when the two groups were compared. The number of mature oocytes and the fertilization rates were similar in both groups; however, the number of grade 1 (G1 embryos and the number of transferred embryos were higher in the agonist group. Implantation rates were significantly higher in the antagonist group compared to the agonist group. Pregnancy rates/embryo transfer rates were higher in the antagonist group; however, this difference was not statistically significant (32.8% for agonist group vs. 39.1% for antagonist group, P>0.05. Conclusion The present study showed that applying GnRH-agonist and GnRH-antago- nist protocols to coasted cycles did not result in any differences in cycle parameters and clinical pregnancy rates.

  17. Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study.

    Science.gov (United States)

    Toida, Tatsunori; Fukudome, Keiichi; Fujimoto, Shouichi; Yamada, Kazuhiro; Sato, Yuji; Chiyotanda, Susumu; Kitamura, Kazuo

    2012-09-01

    Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out. After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses. The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease. LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

  18. Effects of HA released calcium ion on osteoblast differentiation.

    Science.gov (United States)

    Jung, Gil-Yong; Park, Yoon-Jeong; Han, Jung-Suk

    2010-05-01

    Hydroxyapatite (HA) is a widely used calcium phosphate implant substitute and has dissolution property. Although HA has been shown a beneficial effect on osteoblast differentiation, the exact mechanism is still unclear. In the present study, we proposed that Ca(2+) released from HA activated the expression bone associated proteins, OPN and BSP, mediated by L-type calcium channel and calcium/calmodulin-dependent protein kinase (CaMK) 2 which resulted into improved osteoblast differentiation. Results showed that HA elevated ALP expression as well as OPN and BSP expression in MC3T3-E1 cells. The result from western blot of CaMK2alpha indicated that HA released Ca(2+) activated CaMK2 through L-type calcium channel. Furthermore, upregulation of OPN and BSP mRNA expression was significantly inhibited when blocking both the L-type calcium channel and CaMK2. These findings suggested that HA accelerated the osteoblast differentiation by releasing Ca(2+).

  19. Effects of autacoid inhibitors and of an antagonist on malaria infection in mice

    Directory of Open Access Journals (Sweden)

    E.O. Iwalewa

    2004-08-01

    Full Text Available The effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (CQ in Vom strains of Swiss albino mice (18-22 g of either sex infected intraperitoneally with 1 x 10(7 Plasmodium yoelii nigeriensis-induced malaria. As prophylactic, these agents reduced from 31.9 ± 4.5 to 16.1 ± 8.1% the level of parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 ± 5.8 to 4.9 ± 0.75% the level of parasitemia (P < 0.05, which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the parasitemia load (the extent of damage and the severity of infection as well as enhance the effects of CQ when combined with it for malaria therapy. The study reveals that the production of autacoids in established infection renders autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local hormones implicated in the pathological manifestations of malaria infection by autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of infection and the associated tissue damage and to enhance the efficacy of available anti-malarials.

  20. Effects of dietary oil sources and calcium : phosphorus levels on ...

    African Journals Online (AJOL)

    Elizabeth Stewart

    2016-02-20

    Feb 20, 2016 ... The study investigated the effects of varying dietary calcium (Ca) levels and sources of oil on ... Formation of soluble soap may render the fatty acids and .... Wheat pollard. 97.7. 68.8. 38.9. 97.7. 68.8. 38.9. 97.7. 68.8. 38.9. MDCP3 21%. 15.9. 22.8. 29.8. 15.9. 22.8. 29.8. 15.9. 22.8. 29.8. Calcium carbonate.

  1. Effect of fuel characteristics on synthesis of calcium hydroxyapatite ...

    Indian Academy of Sciences (India)

    The effect of fuel characteristics on the processing of nano sized calcium hydroxyapatite (HA) fine powders by the solution combustion technique is reported. Urea, glycine and glucose were used as fuels in this study. By using different combinations of urea and glycine fuels and occasional addition of small amounts of ...

  2. The effects of calcium regulation of endosperm reserve protein ...

    African Journals Online (AJOL)

    The effects of steep liquor calcium ion on sorghum endosperm reserve protein mobilization were evaluated using two improved Nigeria sorghum cultivars (ICSV 400 and KSV 8). The key protein modification factors evaluated were free amino nitrogen (FAN), total non protein nitrogen (TNPN) and soluble protein of cold water ...

  3. 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.

  4. The Effect of Calcium Phosphate‑containing Desensitizing Agent on ...

    African Journals Online (AJOL)

    2017-09-14

    Sep 14, 2017 ... control), Group 3: TMD/self-etch, Group 4: Acid-etch/TMD/etch and rinse. For microleakage test, Class V adhesive cavities (3 .... purpose of this study was to evaluate the effect of calcium phosphate-containing ..... patented technique for the total-etch procedure occurs before oxalate and adhesive placement.

  5. Effects of calcium gluconate and ascorbic acid on controlling shoot ...

    African Journals Online (AJOL)

    In vitro shoot necrosis is a quite widespread disorder affecting raspberry micropropagation. This study was conducted to investigate effects of calcium gluconate and ascorbic acid on shoot necrosis and dieback of raspberry shoots during micropropagation. Nodal segments of primocane-fruiting raspberry cultivars 'Allgold', ...

  6. The effect of calcium phosphate-containing desensitizing agent on ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to investigate the effect of calcium phosphate containing desensitizing pretreatments on the microtensile bond strength (MTBS) and microleakage of the multimode adhesive agent to dentin. Materials and Methods: In this study, twelve noncarious, freshly extracted human third molar teeth ...

  7. The effect of farmyard manure and calcium ammonium nitrate on ...

    African Journals Online (AJOL)

    The effect of farmyard manure and calcium ammonium nitrate on vegetative growth, leaf yield and nutritive quality of Cleome gynadra (Cat Whiskers) in Keiyo District, ... extension workers and farmers, are receiving renewed interest as a possible intervention to food insecurity and malnutrition among resource-poor farmers.

  8. A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Wenbo Yao

    2017-08-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

  9. The influence of microbial synergistic and antagonistic effects on the performance of refinery wastewater microbial fuel cells

    Science.gov (United States)

    Guo, Xuan; Zhan, Yali; Chen, Chunmao; Zhao, Lijie; Guo, Shaohui

    2014-04-01

    This study provides a preliminary investigation of the synergistic and antagonistic effects of different microbial strains and their influence on electricity generation and wastewater treatment performances in microbial fuel cells (MFCs). Microbial metabolic characteristics of petroleum hydrocarbon pollutants are studied simultaneously to provide further insight into how microbial synergistic and antagonistic effects influence MFCs. We observed a synergistic effect between Paenibacillus sp. and Deinococcus sp. and an antagonistic effect between Microbacterium sp. and Paenibacillus sp. and Deinococcus sp. The microbial synergistic and antagonistic effects significantly influenced MFC performance directly. The best MFC performance was observed with Paenibacillus sp. + Deinococcus sp. due to their synergistic effect, where the power density output reached 102.93 mW m-3, and the oil removal rate was 85.56 ± 1.10%. However, the performances of MFCs inoculated with Microbacterium sp. were considerably poorer because of its antagonistic effect on the other microbial strains, where the lowest power density output was 24.93 mW m-3, and the oil removal rate was 65.88 ± 1.10%. The degradation characteristics of petroleum hydrocarbons differ between microbial strains; thus, the relative results can provide further insight into how microbial synergistic and antagonistic effects influence MFCs.

  10. Síntesis de nuevos derivados de hexahidroquinoleínas y evaluación farmacológica de sus propiedades antagonistas del calcio Synthesis of new hexahydroquinoline derivatives and pharmacological evaluation of their calcium antagonist properties

    Directory of Open Access Journals (Sweden)

    Loipa Galán Martínez

    2006-12-01

    Full Text Available Se prepararon cinco hexahidroquinoleínas por una síntesis en un solo paso, a partir de un aldehído aromático, el ß -aminocrotonato de alquilo (enamina y dimedona en etanol absoluto como disolvente. Se caracterizaron los efectos de las cinco hexahidroquinoleínas sobre la contractilidad en anillos de aorta de conejo y sobre la contractilidad de músculos papilares de ventrículo derecho de rata, de manera comparativa con la clásica nifedipina. Todas las hexahidroquinoleínas inhibieron la actividad contráctil tanto en músculo liso vascular como en músculo cardíaco, y mostraron efectos característicos de compuestos antagonistas del calcio, aunque con menor potencia de acción que la nifedipina. Sin embargo, dos de las hexahidroquinoleínas estudiadas presentaron cierta vasoselectividad, aunque no marcada.Five hexahydroquinolines were prepared through one-step synthesis from an aromatic aldehyde called ß- alkyl aminocrotonate (enaminand dimedone in pure ethanol as solvent. The effects of the five hexahydroquinolines on contractility of rabitt´s aorta rings and on contractility of papillar muscles of rat´s right ventricle were characterized in a comparative way to classical nifedipine. All hexahydroquinolines inhibited the contractile activity of both vascular smooth muscle and cardiac muscle, and they showed effects that are characteristic of calcium antagonist compounds, although with less potent action than nifedipine. However, two of the studied hexahydroquinolines presented some mild vasoselectivity.

  11. 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.

  12. 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...

  13. 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...... in microdialysate levels of glycerol illustrating an acute stimulation of lipolysis. No equivalent increase in glycerol was, however, observed in vitro following incubation of isolated rat adipocytes with rimonabant. This finding excludes a direct lipolytic action of rimonabant on tissue level. Instead...

  14. 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.

  15. 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. Copyright © 2012 American Society for Bone and Mineral Research.

  16. Effects of NMDA receptor antagonists on probability discounting depend on the order of probability presentation.

    Science.gov (United States)

    Yates, Justin R; Breitenstein, Kerry A; Gunkel, Benjamin T; Hughes, Mallory N; Johnson, Anthony B; Rogers, Katherine K; Shape, Sara M

    Risky decision making can be measured using a probability-discounting procedure, in which animals choose between a small, certain reinforcer and a large, uncertain reinforcer. Recent evidence has identified glutamate as a mediator of risky decision making, as blocking the N-methyl-d-aspartate (NMDA) receptor with MK-801 increases preference for a large, uncertain reinforcer. Because the order in which probabilities associated with the large reinforcer can modulate the effects of drugs on choice, the current study determined if NMDA receptor ligands alter probability discounting using ascending and descending schedules. Sixteen rats were trained in a probability-discounting procedure in which the odds against obtaining the large reinforcer increased (n=8) or decreased (n=8) across blocks of trials. Following behavioral training, rats received treatments of the NMDA receptor ligands MK-801 (uncompetitive antagonist; 0, 0.003, 0.01, or 0.03mg/kg), ketamine (uncompetitive antagonist; 0, 1.0, 5.0, or 10.0mg/kg), and ifenprodil (NR2B-selective non-competitive antagonist; 0, 1.0, 3.0, or 10.0mg/kg). Results showed discounting was steeper (indicating increased risk aversion) for rats on an ascending schedule relative to rats on the descending schedule. Furthermore, the effects of MK-801, ketamine, and ifenprodil on discounting were dependent on the schedule used. Specifically, the highest dose of each drug decreased risk taking in rats in the descending schedule, but only MK-801 (0.03mg/kg) increased risk taking in rats on an ascending schedule. These results show that probability presentation order modulates the effects of NMDA receptor ligands on risky decision making. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. 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...

  18. The effect of calcium channel blockers and calmodulin inhibitors on the macrophage factor-stimulated synthesis of collagenase by rabbit chondrocytes.

    Science.gov (United States)

    Nolan, J C; Gathright, C E; Wagner, L E

    1988-08-01

    Macrophages and monocytes secrete a factor(s) which can stimulate the synthesis of collagenase in synovial cells and in chondrocytes. Incubation of rabbit chondrocytes with macrophage conditioned medium (MCM) and with the calcium channel blockers, nifedipine, verapamil or diltiazem (up to 200 microM) had no effect on collagenase synthesis. However, TMB-8 (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), an inhibitor of internal calcium movement, did inhibit the process with an IC50 of approximately 130 microM. The calmodulin antagonists, trifluoperazine, chlorpromazine and calmidazolium (R-24571) were effective inhibitors of the process with IC50's of 40 microM, 18 microM and 3.5 microM, respectively. Collagenase activity itself was not affected by these agents. The data suggests that calmodulin and/or internal calcium movement may play a role in the macrophage factor-stimulated synthesis of collagenase in rabbit chondrocytes.

  19. 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.

  20. Differential effects of calcium antagonist subclasses on markers of nephropathy progression

    National Research Council Canada - National Science Library

    Bakris, George L; Weir, Matthew R; Secic, Michelle; Campbell, Brett; Weis-McNulty, Annette

    2004-01-01

    ... studies have shown that higher levels of proteinuria are associated with increased progression of renal and cardiovascular disease and that reductions in proteinuria are associated with a decrease in the rate of renal function deterioration and cardiovascular events. As a result of this relationship, proteinuria is frequently used as a surrogate end po...

  1. 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.

  2. The effect of brushing with nano calcium carbonate and calcium carbonate toothpaste on the surface roughness of nano-ionomer

    Science.gov (United States)

    Anisja, D. H.; Indrani, D. J.; Herda, E.

    2017-08-01

    Nanotechnology developments in dentistry have resulted in the development of nano-ionomer, a new restorative material. The surface roughness of restorative materials can increase bacteria adhesion and lead to poor oral hygiene. Abrasive agents in toothpaste can alter tooth and restorative material surfaces. The aim of this study is to identify the effect of brushing with nano calcium carbonate, and calcium carbonate toothpaste on surface roughness of nano-ionomer. Eighteen nano-ionomer specimens were brushed with Aquabidest (doubledistilled water), nano calcium carbonate and calcium carbonate toothpaste. Brushing lasted 30 minutes, and the roughness value (Ra) was measured after each 10 minute segment using a surface roughness tester. The data was analyzed using repeated ANOVA and one-way ANOVA test. The value of nano-ionomer surface roughness increased significantly (p<0.05) after 20 minutes of brushing with the nano calcium carbonate toothpaste. Brushing with calcium carbonate toothpaste leaves nano-ionomer surfaces more rugged than brushing with nano calcium carbonate toothpaste.

  3. Cutaneous Penetration-Enhancing Effect of Menthol: Calcium Involvement.

    Science.gov (United States)

    Joshi, Amit; Joshi, Abhay; Patel, Hiren; Ponnoth, Dovenia; Stagni, Grazia

    2017-07-01

    Menthol is a naturally occurring terpene used as a penetration enhancer in topical and transdermal formulations. Literature shows a growing interest in menthol's interactions with the transient receptor potential melastatin 8. A decrease in extracellular Ca 2+ due to the activation of the transient receptor potential melastatin 8 receptor produces inhibition of E-cadherin expression that is responsible for cell-cell adhesion. Because calcium is present in the entire epidermis, the purpose of this study is to evaluate whether the aforementioned properties of menthol are also related to its penetration-enhancing effects. We formulated 16 gels: (i) drug-alone (diphenhydramine or lidocaine), (ii) drug with menthol, (iii) drug, menthol, and calcium channel blocker (CCB; verapamil or diltiazem), and (iv) drug and CCB. In vitro studies showed no effect of the CCB on the release of the drugs either with or without menthol. In vivo experiments were performed for each drug/menthol/CCB combination gel by applying 4 formulations on a shaved rabbit's dorsum on the same day. Dermis concentration profiles were assessed with microdialysis. The gels containing menthol showed higher penetration of drugs than those without whereas the addition of the CCB consistently inhibited the penetration-enhancing effects of menthol. In summary, these findings strongly support the involvement of calcium in the penetration-enhancing effect of menthol. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. Effects of dietary oil sources and calcium : phosphorus levels on ...

    African Journals Online (AJOL)

    The study investigated the effects of varying dietary calcium (Ca) levels and sources of oil on performance of broiler chickens. A total of 378 one-day-old birds were fed 6% palm oil (PO), soybean oil (SO) or linseed oil (LO) in combination with three levels of Ca, 1%, 1.25% and 1.5%, for six weeks in a 3 x 3 factorial ...

  6. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.

    2011-01-01

    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  7. Effects of high affinity leptin antagonist on prolactin receptor deficient male mouse.

    Directory of Open Access Journals (Sweden)

    Nadège Carré

    Full Text Available Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL induces the expression of orexigenic neuropeptide Y (NPY in hypothalamic dorsomedial nucleus (DMH leading to hyperphagia. Along this line prolactin receptor deficient (PRLR-/- mice are resistant to obesity under high fat diet due to increased energy expenditure. As these mice have an altered food intake, our objective was to test whether leptin is responsible for these characteristics. PRLR-/- male mice and control littermates were injected subcutaneously every other day with 12 mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA for 3 weeks. We tested the effect of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist led to a rapid increase in body weight (20% but increased adipose mass in PEG-SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of PEG-SMLA-injected animals increased during the first week period of the experiment but then declined to a similar level of the control animals during the second week. Interestingly, PRLR-/- mice were found to have the same bone volume than those of control mice although PEG-SMLA increased bone mass by 7% in both strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance as well as an altered lipid profile in treated mice. Altogether, these results suggest that PRLR-/- mice respond to leptin antagonist similarly to the control mice, indicating no interaction between the actions of the two hormones.

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

    Directory of Open Access Journals (Sweden)

    Prabhakaran Priyaja

    2014-01-01

    Full Text Available Objective: To abrogate pathogenic vibrios in aquaculture by testing the potential of Pseudomonas isolates from fresh water, brackish and marine environments as probiotics. Methods: Purification and structural elucidation of antagonistic compound were carried out. 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 were Pseudomonas 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: The present investigation showed that Pseudomonas aeruginosa MCCB119 would be ideal for application in freshwater, MCCB102 and MCCB103 in brackish water and MCCB117 and MCCB118 in marine aquaculture systems as putative probiotics in the management of vibrios.

  9. Rupatadine: efficacy and safety of a non-sedating antihistamine with PAF-antagonist effects.

    Science.gov (United States)

    Shamizadeh, Soja; Brockow, Knut; Ring, Johannes

    Rupatadine is a modern non-sedating H1-antihistamine that also haswith additional antagonist effects on platelet-activating factor (PAF). Under the tradenames Rupafin® and Urtimed®, Rrupatadine is approvedregistered in Germany for the treatment of allergic rhinitis and urticaria infor adults and children aged over 12 years. In this review, the available literature available to date onregarding the pharmacological profile and clinical application of Rrupatadine is reviewed and compared to other conventional histamines. In conclusionFinally, the side effects, safety and interaction profileincompatibility of Rrupatadine are discussed. Due to CYP p450 metabolism, Rrupatadine should not be given together with Eerythromycin, Kketoconazole or grapefruit juice. Rupatadine has been found to be effective and safe Iin a variety of randomized clinical trials both in both seasonal and perennial allergic rhinitis, as well as inbut also chronic urticaria Rupatadine has been found as effective and safe.

  10. Effect of temperature on antagonistic and biocontrol potential of Trichoderma sp. on Sclerotium rolfsii.

    Science.gov (United States)

    Mukherjee, P K; Raghu, K

    1997-01-01

    Sclerotium rolfsii is a destructive soil-borne and post-harvest plant pathogen. Use of the antagonistic fungus Trichoderma sp. has been earlier reported by us to successfully control this pathogen under post-harvest conditions. In the present paper we report on the effects of temperature on the growth and biocontrol potential of Trichoderma sp. on S. rolfsii. Experimental results indicated that S. rolfsii and Trichoderma sp. have different temperature optima for growth: 30-35 degrees C for the pathogen and 25-30 degrees C for the antagonist. In dual culture, Trichoderma over-grew S. rolfsii at 25 degrees C and 30 degrees C, but at 35 degrees C and 37 degrees C, S. rolfsii over-grew the colony of Trichoderma. Trichoderma produced higher concentration of fungi-toxic metabolites in broth culture at higher temperatures. In bioassays using ginger slices and whole rhizomes, it has been demonstrated that Trichoderma is not very effective in suppressing S. rolfsii at temperatures above 30 degrees C. In light of these results, possible mechanisms of biocontrol of S. rolfsii as a post-harvest pathogen has been discussed. Storage temperature has been suggested as a critical factor in biocontrol of S. rolfsii.

  11. Effects of cannabinoid and glutamate receptor antagonists and their interactions on learning and memory in male rats.

    Science.gov (United States)

    Barzegar, Somayeh; Komaki, Alireza; Shahidi, Siamak; Sarihi, Abdolrahman; Mirazi, Naser; Salehi, Iraj

    2015-04-01

    Despite previous findings on the effects of cannabinoid and glutamatergic systems on learning and memory, the effects of the combined stimulation or the simultaneous inactivation of these two systems on learning and memory have not been studied. In addition, it is not clear whether the effects of the cannabinoid system on learning and memory occur through the modulation of glutamatergic synaptic transmission. Hence, in this study, we examined the effects of the simultaneous inactivation of the cannabinoid and glutamatergic systems on learning and memory using a passive avoidance (PA) test in rats. On the test day, AM251, which is a CB1 cannabinoid receptor antagonist; MK-801, which is a glutamate receptor antagonist; or both substances were injected intraperitoneally into male Wistar rats 30min before placing the animal in a shuttle box. A learning test (acquisition) was then performed, and a retrieval test was performed the following day. Learning and memory in the PA test were significantly different among the groups. The CB1 receptor antagonist improved the scores on the PA acquisition and retention tests. However, the glutamatergic receptor antagonist decreased the acquisition and retrieval scores on the PA task. The CB1 receptor antagonist partly decreased the glutamatergic receptor antagonist effects on PA learning and memory. These results indicated that the acute administration of a CB1 antagonist improved cognitive performance on a PA task in normal rats and that a glutamate-related mechanism may underlie the antagonism of cannabinoid by AM251 in learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  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

    either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium-creatinine ratio...

  13. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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

  15. Potentiation of the antinociceptive effect of clomipramine by a 5-ht1A antagonist in neuropathic pain in rats

    Science.gov (United States)

    Ardid, D; Alloui, A; Brousse, G; Jourdan, D; Picard, P; Dubray, C; Eschalier, A

    2001-01-01

    The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5-HT1A antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug. The purpose of this work was to evaluate the combination of an antidepressant and a 5-HT1A antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipramine and a 5-HT1A antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats). The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5-HT1A antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine. These new findings argue for using the combination of an antidepressant and a 5-HT1A antagonist in human neuropathic pain therapy. PMID:11226143

  16. 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.

  17. Is there a clinically significant interaction between calcium channel antagonists and clopidogrel?: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.

    Science.gov (United States)

    Good, Christopher W; Steinhubl, Steven R; Brennan, Danielle M; Lincoff, A Michael; Topol, Eric J; Berger, Peter B

    2012-02-01

    Clopidogrel is an inactive prodrug; it is converted to its active metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel blockers (CCBs). Several studies have reported that CCBs reduce the ability of clopidogrel to inhibit platelet aggregability; one suggested that CCBs reduce the efficacy of clopidogrel. We performed a post hoc analysis of the Clopidogrel for the Reduction of Events During Observation (CREDO) study to compare the treatment effect of clopidogrel in patients on CCBs versus not on CCBs. In CREDO, 2116 patients were randomly assigned to pretreatment with 300 mg clopidogrel 3-24 hours before a planned percutaneous coronary intervention followed by 1 year of 75 mg/d clopidogrel, versus 75 mg clopidogrel at the time of the procedure and continued for 28 days only. The primary end points were a combined end point of death, myocardial infarction, and stroke at 28 days and 1 year. Among the 580 patients (27%) on CCBs at enrollment, at 28 days, the combined end point was reached in 17 patients (6%) on clopidogrel versus 28 (9%) on placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.39-1.29). At 1 year, the combined end point was reached in 27 patients (10%) on clopidogrel versus 46 (15%) on placebo (HR, 0.68; 95% CI, 0.42-1.09). The treatment effect of clopidogrel was similar in patients not on CCBs at 1 year (HR, 0.78; 95% CI, 0.56-1.09). After adjustment for differences between patients on and not on CCB, there was still no evidence of an interaction between clopidogrel treatment and CCB (HR for patients not on CCBs, 0.87; 95% CI, 0.62-1.23; HR for patients on CCBs, 0.74; 95% CI, 0.45-1.21). In CREDO, there was no evidence that CCBs decrease the efficacy of clopidogrel.

  18. Calcium dobesilate and oxerutin: effectiveness of combination therapy.

    Science.gov (United States)

    Akbulut, B

    2010-04-01

    Chronic venous insufficiency (CVI) is an important cause of discomfort and inability to work. Hydroxyethylrutosides (Venoruton); 0-[beta-hydroxyethyl]-rutosides) has been used for decades for the treatment of CVI. Studies have reported symptomatic relief and a decreased capillary filtration after the administration of the oral preparations. Calcium dobesilate is a synthetic venoactive drug acting on several levels. It inhibits capillary permeability; it has antioxidant properties; and it inhibits the synthesis of prostaglandins and thromboxanes, reducing platelet and erythrocyte aggregation, as well as blood viscosity. The aim of this study is to determine whether the combination of both drugs is more effective in decreasing patients' complaints. One hundred and fifty patients with primary venous insufficiency were randomized into three groups: Group A receiving calcium dobesilate only, Group B receiving oxerutin only and Group C receiving both calcium dobesilate and oxerutin. Patients were evaluated with a questionnaire before and four weeks after treatment regarding following parameters: itching, fatigue, heaviness, numbness, cramp, swelling and sensitiveness. Patients rated their symptoms from 0 to 4 (0: absent; 1: mild; 2: moderate; 3: severe; 4: very severe). Complaints, which were scored by patients before and after treatment, decreased. Among the single-drug groups, itching score decreased more in Group B, whereas scores of fatigue, heaviness, numbness, cramp and swelling decreased more in Group A. But the difference was not significant, statistically. But all complaints decreased significantly in Group C. Difference of scores after treatment revealed no statistical significance in Group A and B, but scores of Group C produced a significant difference when compared with Group A and B. Results demonstrate that a combination of calcium dobesilate and oxerutin shows a better improvement of complaints. These observations have to be confirmed in larger series

  19. Portraying the Effect of Calcium-Binding Proteins on Cytosolic Calcium Concentration Distribution Fractionally in Nerve Cells.

    Science.gov (United States)

    Jha, Brajesh Kumar; Joshi, Hardik; Dave, Devanshi D

    2016-11-23

    Nerve cells like neurons and astrocytes in central nervous system (CNS) take part in the signaling process which means the transformation of the information from one cell to another via signals. The signaling process is affected by various external parameters like buffers calcium-binding proteins, voltage-gated calcium channel. In the present paper, the role of buffers in the cytoplasmic calcium concentration distribution is shown. The elicitation in calcium concentration is due to the presence of lower amount calcium-binding proteins which can be shown graphically. The mathematical model is designed by keeping in mind the physiological condition taking place in CNS of mammalian brain. The thing to be noted here is that the more elicitation in the calcium concentration distribution results in the cell death which finally give neurodegenerative disease to the mammalian brain. The present paper gives a glimpse of Parkinson's diseases in particular. Computational results are performed in Wolfram Mathematica 9.0 and simulated on core(TM) i5-3210M CPU @ 2.50 GHz processing speed and 4 GB memory. It is found that the different types of buffer like ethylene glycol-bis([Formula: see text]-aminoethyl ether)-N,N,N',N'-tetraacetic acid, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and calmodulin have noteworthy effect at different fractions of time.

  20. Effect of Calcium Chloride on the Preparation of Low-fat Spreads ...

    African Journals Online (AJOL)

    associated with lower bone mineral density [4]. Nutritionally sufficient levels of calcium in the diet are strongly related to the intake of dairy products, which are the richest sources of highly bioavailable calcium [5]. Therefore, the objective of this work was to study the effects of calcium chloride on sensory, morphological ...

  1. Effects of calcium paste as a seed coat on growth, yield and ...

    African Journals Online (AJOL)

    MK

    2012-09-25

    Sep 25, 2012 ... NaCl stress reduced plant growth, photosynthetic pigment levels, ascorbic acid and calcium contents, and the activities of ... effects of calcium paste as a seed coat in mitigating the phytotoxicity of NaCl stress in pea plants. Key words: Calcium paste, ..... of saline water on tomato plants. Fayoum J. Agric. Res.

  2. Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.

    Science.gov (United States)

    Epstein, David H; Kennedy, Ashley P; Furnari, Melody; Heilig, Markus; Shaham, Yavin; Phillips, Karran A; Preston, Kenzie L

    2016-12-01

    In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. To test anticraving properties of the CRF1 antagonist pexacerfont in humans. We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS). The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (r effect = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect = 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics. The findings may support further investigation of the anticraving properties of CRF1 antagonists, especially for food.

  3. Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

    Science.gov (United States)

    Asplin, John R.; Frick, Kevin K.; Granja, Ignacio; Culbertson, Christopher D.; Ng, Adeline; Grynpas, Marc D.; Bushinsky, David A.

    2015-01-01

    Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

  4. Protective effects of calcium from nonfat dried milk against colon carcinogenesis in rats.

    Science.gov (United States)

    Pence, B C; Dunn, D M; Zhao, C; Patel, V; Hunter, S; Landers, M

    1996-01-01

    A number of studies have demonstrated the protective effect of dietary calcium against risk for colon cancer. The objective of this experimental study was to test the efficacy of two sources of dietary calcium, elemental calcium in the form of CaCO3 and dairy calcium as nonfat dried milk (NFDM), in colon tumor inhibition. Male weanling F344 rats were fed six test diets containing low (LF, 5%) and high (HF, 20%) levels of corn oil and low (0.5%) and high (1.0%) levels of calcium supplemented as CaCO3 or NFDM in a 2 x 3 factorial design. Tumors were induced with two weekly injections of azoxymethane at 12 mg/kg body wt. After 27 weeks on the test diets, animals were necropsied for tumor analysis. There was no difference in tumor incidence for fat or calcium source main effects, but a significant interaction was seen between fat and calcium source, with the lowest tumor incidence seen in the HF/NFDM group. Calcium compartmentalization studies demonstrated no effects of calcium on serum calcium levels but increased urinary and fecal water calcium in the higher-calcium diets. Increased dietary calcium also decreased fecal bile acid concentrations, but there was no effect on fecal water bile acids. Intermediate biomarkers of colon carcinogenesis were not affected by the dietary treatments except for fat effects on carcinogen-induced nuclear aberrations. These results indicate that source of calcium is not critical but that total dietary context may affect efficacy of calcium against colon carcinogenesis.

  5. 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.

  6. 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

  7. 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.

  8. Effects of microgravity on bone and calcium homeostasis

    Science.gov (United States)

    Zérath, E.

    Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns, and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequenccy and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and ``simulated'' spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.

  9. 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

  10. Ecologically relevant levels of multiple, common marine stressors suggest antagonistic effects.

    Science.gov (United States)

    Lange, Rolanda; Marshall, Dustin

    2017-07-24

    Stressors associated with global change will be experienced simultaneously and may act synergistically, so attempts to estimate the capacity of marine systems to cope with global change requires a multi-stressor approach. Because recent evidence suggests that stressor effects can be context-dependent, estimates of how stressors are experienced in ecologically realistic settings will be particularly valuable. To enhance our understanding of the interplay between environmental effects and the impact of multiple stressors from both natural and anthropogenic sources, we conducted a field experiment. We explored the impact of multiple, functionally varied stressors from both natural and anthropogenic sources experienced during early life history in a common sessile marine invertebrate, Bugula neritina. Natural spatial environmental variation induced differences in conspecific densities, allowing us to test for density-driven context-dependence of stressor effects. We indeed found density-dependent effects. Under high conspecific density, individual survival increased, which offset part of the negative effects of experiencing stressors. Experiencing multiple stressors early in life history translated to a decreased survival in the field, albeit the effects were not as drastic as we expected: our results are congruent with antagonistic stressor effects. We speculate that when individual stressors are more subtle, stressor synergies become less common.

  11. Effect of flunarizine and calcium on serotonin uptake in human and rat blood platelets and rat synaptosomes

    DEFF Research Database (Denmark)

    Jensen, P N; Smith, D F; Poulsen, J H

    1994-01-01

    Calcium and the calcium overload blocker flunarizine exert profound effects on mood. We therefore studied the effect of calcium and flunarizine on serotonin uptake in human and rat blood platelets and in rat synaptosomes. Calcium (1.3 mmol/L) had a weak inhibiting effect on serotonin uptake in bl...

  12. Effects of elevated calcium on motor and exploratory activities of rats

    Directory of Open Access Journals (Sweden)

    Godinho A.F.

    2002-01-01

    Full Text Available The effects of serum and brain calcium concentration on rat behavior were tested by maintaining animals on either distilled water (N = 60 or water containing 1% calcium gluconate (N = 60 for 3 days. Animals that were maintained on high calcium drinking water presented increased serum calcium levels (control = 10.12 ± 0.46 vs calcium treated = 11.62 ± 0.51 µg/dl. Increase of brain calcium levels was not statistically significant. In the behavioral experiments each rat was used for only one test. Rats that were maintained on high calcium drinking water showed increased open-field behavior of ambulation (20.68% and rearing (64.57%. On the hole-board, calcium-supplemented animals showed increased head-dip (67% and head-dipping (126%, suggesting increased ambulatory and exploratory behavior. The time of social interaction was normal in animals maintained on drinking water containing added calcium. Rats supplemented with calcium and submitted to elevated plus-maze tests showed a normal status of anxiety and elevated locomotor activity. We conclude that elevated levels of calcium enhance motor and exploratory behavior of rats without inducing other behavioral alterations. These data suggest the need for a more detailed analysis of several current proposals for the use of calcium therapy in humans, for example in altered blood pressure states, bone mineral metabolism disorders in the elderly, hypocalcemic states, and athletic activities.

  13. [Effect of antagonistic bacteria and soil disinfectant on soil bacterium community in banana Fusarium wilt disease area].

    Science.gov (United States)

    Zhou, Dengbo; Jing, Tao; Tan, Xin; Chen, Bo; Zhang, Xiyan; Gao, Zhufen

    2013-08-04

    The objective of the present study is to elucidate the effects of the application of cake fertilizer fermentation fluid with antagonistic bacteria and soil disinfectant chlorine dioxide on the occurrence of banana fusarium wilt disease and soil bacterium community. Under the field cultivation conditions, the Biolog and T-RFLP method was used to investigate the soil bacterium diversity and community features in different treatments at different periods. The results show that both cake fertilizer fermentation fluid with antagonistic bacteria and soil disinfectant could reduce disease index of banana fusarium wilt disease significantly, the highest control effect could reach 60.82% with the combined application of these two methods. The result of Biolog eco plate shows that the application of cake fertilizer fermentation fluid with antagonistic bacteria could improve soil microbial AWCD (average well color development) and population uniformity, the use of soil disinfectant significantly reduced the soil microbial population's abundance and the uniformity. Principal component analysis shows that the soil microbial population using carbon source had an increasing trend throughout the banana growing season, the main carbon sources in the early stage were amino acids, carboxylic acids, amphiphilic compounds and carbohydrates, and the increased main carbon sources in the later stage were carboxylic acids and amphiphilic compounds. Soil bacterial diversity analysis by T-RFLP shows that the treatments of cake fertilizer fermentation fluid with antagonistic bacteria had the highest bacterial TRFs (Terminal restriction fragment) fragments, which resulted from the increase of Flavobacterium, Pseudomona and Lactobacillus population in the soil. The application of cake fertilizer fermentation fluid with antagonistic bacteria combining soil disinfectant could increase antagonistic microorganisms species, enhance soil microbial diversity, improve soil microbial ecological

  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. Differential effects of organic calcium-channel blockers on diastolic SR calcium-handling in the frog heart.

    Science.gov (United States)

    Subramani, Sathya; Vijayanand, Caroline; Tharion, Elizabeth

    2002-11-01

    1. Gradual loss of sarcoplasmic reticular (SR) calcium during a rest-period is responsible for the rest-induced decay (RID) of force in mammalian myocardium. Effect of verapamil and diltiazem on a similar RID in the frog myocardium suggests a new mechanism of action of these drugs. 2. Strips of frog-ventricle were paced at 0.2 Hz and the rhythm was interrupted by varying rest-periods ranging from 10 to 180 s. In control conditions, the amplitude of the post-rest beat was significantly lower than that of the pre-rest beat for rest-periods more than 40 s (RID). 3. Verapamil and diltiazem (which are organic calcium-channel blockers (OCCB)) changed the pattern of RID in the control solution to a 'rest-induced potentiation' (RIP) in the same preparation while another OCCB nifedipine and the inorganic calcium-channel blocker cadmium did not alter the post-rest phenomenon. 4. We propose that verapamil and diltiazem produce an RIP due to either blockade of SR calcium-leak during rest or enhancement of SR calcium-uptake during rest.

  16. Effects of calcium at toxic concentrations of cadmium in plants.

    Science.gov (United States)

    Huang, Danlian; Gong, Xiaomin; Liu, Yunguo; Zeng, Guangming; Lai, Cui; Bashir, Hassan; Zhou, Lu; Wang, Dafei; Xu, Piao; Cheng, Min; Wan, Jia

    2017-05-01

    This review provides new insight that calcium plays important roles in plant growth, heavy metal accumulation and translocation, photosynthesis, oxidative damage and signal transduction under cadmium stress. Increasing heavy metal pollution problems have raised word-wide concerns. Cadmium (Cd), being a highly toxic metal, poses potential risks both to ecosystems and human health. Compared with conventional technologies, phytoremediation, being cost-efficient, highly stable and environment-friendly, is believed to be a promising green technology for Cd decontamination. However, Cd can be easily taken up by plants and may cause severe phytotoxicity to plants, thus limiting the efficiency of phytoremediation. Various researches are being done to investigate the effects of exogenous substances on the mitigation of Cd toxicity to plants. Calcium (Ca) is an essential plant macronutrient that involved in various plant physiological processes, such as plant growth and development, cell division, cytoplasmic streaming, photosynthesis and intracellular signaling transduction. Due to the chemical similarity between Ca and Cd, Ca may mediate Cd-induced physiological or metabolic changes in plants. Recent studies have shown that Ca could be used as an exogenous substance to protect plants against Cd stress by the alleviation of growth inhibition, regulation of metal uptake and translocation, improvement of photosynthesis, mitigation of oxidative damages and the control of signal transduction in the plants. The effects of Ca on toxic concentrations of Cd in plants are reviewed. This review also provides new insight that plants with enhanced Ca level have improved resistance to Cd stress.

  17. The Yin and Yang of Calcium Effects on Synaptic Vesicle Endocytosis

    Science.gov (United States)

    Wu, Xin-Sheng

    2014-01-01

    A large number of studies suggest that calcium triggers and accelerates vesicle endocytosis at many synapses and non-neuronal secretory cells. However, many studies show that prolonging the duration of the stimulation train, which induces more calcium influx, slows down endocytosis; and several studies suggest that instead of triggering endocytosis, calcium actually inhibits endocytosis. Here we addressed this apparent conflict at a large nerve terminal, the calyx of Held in rat brainstem, in which recent studies suggest that transient calcium increase up to tens of micromolar concentration at the micro/nano domain triggers endocytosis. By dialyzing 0–1 μm calcium into the calyx via a whole-cell pipette, we found that slow endocytosis was inhibited by calcium dialysis in a concentration-dependent manner. Thus, prolonged, small, and global calcium increase inhibits endocytosis, whereas transient and large calcium increase at the micro/nano domain triggers endocytosis and facilitates endocytosis. This yin and yang effect of calcium may reconcile apparent conflicts regarding whether calcium accelerates or inhibits endocytosis. Whether endocytosis is fast or slow depends on the net outcome between the yin and yang effect of calcium. PMID:24523554

  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. Effects of nucleus accumbens oxytocin and its antagonist on social approach behavior.

    Science.gov (United States)

    Yu, Cheng J; Zhang, Shu W; Tai, Fa D

    2016-12-01

    Severe impairment of social interaction is a core symptom of numerous psychiatric disorders. Oxytocin (OT) has been shown to be involved in various aspects of social behavior related to reproduction, but little is known about its effects on nonreproductive social interaction between adults or the neuroanatomical location where OT exerts its action. Here, we examined the nucleus accumbens, a region of the brain containing high levels of the oxytocin receptor (OTR) and comprising an important node in the neural circuitry possibly related to social interaction. Behavioral effects of a local microinfusion of OT (0.1, 1, and 10 ng/side) and an oxytocin receptor antagonist (OTR-A) (1, 10, and 100 ng/side) were evaluated in naturally high social and low social female and male monogamous mandarin voles (Microtus mandarinus) using the social preference paradigm and open-field tests. The results showed that administration of 1 ng/side OT increased social preference; however, this effect was not apparent at lower or higher doses. OT did not alter anxiety-like behavior or total locomotion. Microinfusions of a selective OTR-A at 10 and 100 ng doses reduced social approach behavior; a dose of 1 ng had no effect. In conclusion, our results suggest that accumbal OT and OTR-A regulate social preferences in voles in a dose-dependent manner.

  20. Antagonistic Effect of Laver, Pyropia yezonensis and P. haitanensis, on Subchronic Lead Poisoning in Rats.

    Science.gov (United States)

    Guo, Yingying; Gu, Xiaohui; Jiang, Yanhua; Zhu, Wenjia; Yao, Lin; Liu, Zhantao; Gao, Hua; Wang, Lianzhu

    2017-06-03

    Lead, one of the most harmful heavy metals, can cause various hazardous effects on living organisms. This study was undertaken to evaluate the antagonistic and protective effects of two economically important laver species, Pyropia yezoensis and P. haitanensis, against subchronic lead poisoning in rats by a 30-day feeding test. Sixty-four healthy Wistar rats were randomly divided into eight groups with eight rats (4♂ + 4♀) per group, among which, one group was served as the control, the others were respectively treated with lead acetate (5 mg/kg b w), and a combination of lead acetate and P. yezoensis or P. haitanensis at different dosages. Weight gain of rats was observed and recorded. Changes in antioxidant indexes, and liver and renal function markers were determined to evaluate the antagonistic effect. Lead content in rats was determined to investigate lead excretion effect of laver. The results showed that exposure to lead caused lead accumulation in kidney and liver, thus leading to significant oxidative damage and impaired liver and renal function compared to the control group. The co-treatment of laver slightly increased body weight compared to the lead-treated group. The co-administration of laver restored liver and renal function of rats by preventing the increment in the activities of alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST), and the levels of blood urea nitrogen (BUN) and creatinine (Cr). The increasing of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and lowering of the enhanced malondialdehyde (MDA) contents of rats were observed in the laver co-treated groups, which indicated that laver enhanced the antioxidative capacity of rats. The laver also enhanced lead content in feces and reduced it in liver and kidney. The results indicated that P. yezoensis and P. haitanensis could maintain or promote the normal physiological and biochemical function of lead

  1. [Effects of MAPK antagonist on TPO stimulated UT2 cells proliferation and differentiation].

    Science.gov (United States)

    Li, Wen-lin; Shi, Xiao-yu; Li, Rong; Tang, Hong-lin

    2005-05-01

    To explore the effects of MAPK antagonist on TPO stimulated UT7 cell proliferation and differentiation, and to elucidate the mechanism of TPO functioning on UT7 cells. EGFP pMSCV and MEK 1 pMSCV MEK 1 plasmids were transferred into UT7 cells. Phosphorylated MEK1 of UT7 cells was examined by Western blot. The proliferation and CD41 expression of UT7 cells transfected with mutant (ser222A) MEK1 or exposed to PD98059 were examined. (1) 60.73% EGFP positive cells were obtained in retroviral vector MEK1 pMSCV transfected UT7cells. (2) In different time of TPO stimulating UT7 cells, the level of phosphorylated MEK1 was lower in experiment group than in control group. In experiment group, the level of phosphorylated MEK1 was decreased after stimulated by TPO for 1 hour, and almost disappeared after stimulated for 3 hours. (3) The effect of TPO on UT7 cell proliferation was inhibited by PD98059 and the transfected mutation MEK1 gene. The proliferation rate was 98.58% in DMSO control group, 39.00% in PD98059 group (P TPO. There was a relationship between the TPO stimulating time and phosphorylation of MEK1. The effects of TPO on UT7 cell proliferation and CD41 expression is mediated by MAPK signal transduction pathway.

  2. Antagonistic effect of Lactobacillus strains against gas-producing coliforms isolated from colicky infants.

    Science.gov (United States)

    Savino, Francesco; Cordisco, Lisa; Tarasco, Valentina; Locatelli, Emanuela; Di Gioia, Diana; Oggero, Roberto; Matteuzzi, Diego

    2011-06-30

    Infantile colic is a common disturb within the first 3 months of life, nevertheless the pathogenesis is incompletely understood and treatment remains an open issue. Intestinal gas production is thought to be one of the causes of abdominal discomfort in infants suffering from colic. However, data about the role of the amount of gas produced by infants' colonic microbiota and the correlation with the onset of colic symptoms are scanty. The benefit of supplementation with lactobacilli been recently reported but the mechanisms by which they exert their effects have not yet been fully defined. This study was performed to evaluate the interaction between Lactobacillus spp. strains and gas-forming coliforms isolated from stools of colicky infants. Strains of coliforms were isolated from stools of 45 colicky and 42 control breastfed infants in McConkey Agar and identified using PCR with species-specific primers, and the BBL™ Enterotube™ II system for Enterobacteriaceae. Gas-forming capability of coliforms was assessed in liquid cultures containing lactose as sole carbon source. The average count of total coliforms in colicky infants was significantly higher than controls: 5.98 (2.00-8.76) log10 vs 3.90 (2.50-7.10) CFU/g of faeces (p = 0.015). The following strains were identified: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae and Enterococcus faecalis. Then, 27 Lactobacillus strains were tested for their antagonistic effect against coliforms both by halo-forming method and in liquid co-cultures. Lactobacillus delbrueckii subsp. delbrueckii DSM 20074 and L. plantarum MB 456 were able to inhibit all coliforms strains (halo-forming method), also in liquid co-cultures, thus demonstrating an antagonistic activity. This study shows that two out of 27 strains of Lactobacillus examined possess an antimicrobial effect against six species of gas-forming coliforms isolated from colicky infants. Our findings may stimulate

  3. Effects of the selective 5-HT(7) receptor antagonist SB-269970 in animal models of psychosis and cognition.

    Science.gov (United States)

    Waters, Kerry A; Stean, Tania O; Hammond, Beverley; Virley, David J; Upton, Neil; Kew, James N C; Hussain, Ishrut

    2012-03-01

    The 5-hydroxytryptamine7 (5-HT7) receptor is a G-protein coupled receptor for serotonin that has been implicated in the pathophysiology of psychiatric and neurological disorders including anxiety, depression and schizophrenia. A number of studies have attempted to evaluate the potential role of the 5-HT7 receptor in schizophrenia by utilising genetic or pharmacological tools but to date these have provided conflicting results. Here we investigate the effect of a selective 5-HT7 receptor antagonist, SB-269970, in in vivo psychosis and cognition models and relate efficacy to brain exposures of the compound. SB-269970 significantly attenuated amphetamine-induced rearing and circling in rats. A similar effect was observed in an N-methyl d-aspartic acid (NMDA) receptor antagonist driven psychosis model, where SB-269970 significantly reversed phencyclidine-induced hyperlocomotion, rearing and circling; although the effect was not as robust as with the 5-HT2a receptor antagonist positive control, MDL100,907. SB-269970 also attenuated a temporal deficit in novel object recognition (NOR), indicative of an improvement in recognition memory. Pharmacokinetic analysis of plasma and brain samples taken after behavioural testing confirmed that efficacy was achieved at doses and pre-treatment times where receptor occupancy was substantial. These findings highlight the anti-psychotic and pro-cognitive potential of 5-HT7 receptor antagonists and warrant further studies to explore their therapeutic potential in schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines.

    Science.gov (United States)

    Wang, Shihang; Liu, Chao; Liu, Xinjiang; He, Yanxin; Shen, Dongfang; Luo, Qiankun; Dong, Yuxi; Dong, Haifeng; Pang, Zhigang

    2017-10-01

    Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

  5. Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport.

    Science.gov (United States)

    Takara, Kohji; Sakaeda, Toshiyuki; Kakumoto, Mikio; Tanigawara, Yusuke; Kobayashi, Hironao; Okumura, Katsuhiko; Ohnishi, Noriaki; Yokoyama, Teruyoshi

    2009-01-01

    The purpose of this study is to examine the effects of doxazosin, an alpha-adrenoceptor antagonist, on P-glycoprotein/MDR1-mediated multidrug resistance (MDR) and the transport of anticancer drugs. The effects of doxazosin, prazosin, and terazosin on MDR1-mediated MDR were assessed in human cervical carcinoma HeLa cells and the MDR1-overexpressing derivative Hvrl00-6, established by stepwise increases of the vinblastine concentration in the culture medium. The effects of doxazosin on the transcellular transport and intracellular accumulation of [3H]vinblastine, [3H]daunorubicin, and [3H]digoxin, all MDR1 substrates, were evaluated using LLC-GA5-COL150 cell monolayers, established by transfection of human MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells. The sensitivity to vinblastine and paclitaxel of Hvrl00-6 cells was increased at 3.4- and 17.5-fold, respectively, by the addition of 1 microM doxazosin, whereas prazosin and terazosin had weaker or no such effects. Prazosin at 1 microM had a reversal effect on the sensitivity to vinblastine, whereas terazosin had no effect. In transport experiments, doxazosin concentration dependently increased the apical-to-basal transport of radiolabeled drugs in LLC-GA5-COL150 cells, but did not show remarkable effects on the basal-to-apical transport. In addition, doxazosin restored the intracellular accumulation in a concentration-dependent manner in LLC-GA5-COL150 cells. Doxazosin may partly reverse MDR by inhibiting MDR1-mediated transport, making it a candidate lead compound in the development of a reversing agent for MDR.

  6. Pseudomonas orientalis F9: A Potent Antagonist against Phytopathogens with Phytotoxic Effect in the Apple Flower

    Directory of Open Access Journals (Sweden)

    Veronika Zengerer

    2018-02-01

    Full Text Available In light of public concerns over the use of pesticides and antibiotics in plant protection and the subsequent selection for spread of resistant bacteria in the environment, it is inevitable to broaden our knowledge about viable alternatives, such as natural antagonists and their mode of action. The genus Pseudomonas is known for its metabolic versatility and genetic plasticity, encompassing pathogens as well as antagonists. We characterized strain Pseudomonas orientalis F9, an isolate from apple flowers in a Swiss orchard, and determined its antagonistic activity against several phytopathogenic bacteria, in particular Erwinia amylovora, the causal agent of fire blight. P. orientalis F9 displayed antagonistic activity against a broad suite of phytopathogenic bacteria in the in vitro tests. The promising results from this analysis led to an ex vivo assay with E. amylovora CFBP1430Rif and P. orientalis F9 infected detached apple flowers. F9 diminished the fire blight pathogen in the flowers but also revealed phytotoxic traits. The experimental results were discussed in light of the complete genome sequence of F9, which revealed the strain to carry phenazine genes. Phenazines are known to contribute to antagonistic activity of bacterial strains against soil pathogens. When tested in the cress assay with Pythium ultimum as pathogen, F9 showed results comparable to the known antagonist P. protegens CHA0.

  7. Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium.

    Science.gov (United States)

    Simón, C; Valbuena, D; Krüssel, J; Bernal, A; Murphy, C R; Shaw, T; Pellicer, A; Polan, M L

    1998-11-01

    To investigate the embryonic and/or endometrial molecular mechanisms underlying the antiimplantation effect of interleukin-1 receptor antagonist (IL-1ra). Controlled experiment. Animal facilities at Stanford University and laboratories of the Instituto Valenciano de Infertilidad and the University of Sydney. Twelve-week-old B6C3F-1 female mice. Intraperitoneal injections of recombinant human IL-1ra during the periimplantation period. Implantation sites, embryonic morphology, and viability. Polymerase chain reaction and immunohistochemistry for integrins and extracellular matrices and transmission electron microscopy of endometrium in IL-1ra-treated versus control animals. Pregnancy rates in control and IL-1ra-injected animals were 60% and 13%, respectively. At day 8 of pregnancy, flushing of uteri obtained from the treated group resulted in 32 blastocysts. Six pseudopregnant animals received IL-1ra-treated blastocysts (left horn) and control blastocysts (right horn), resulting in one pregnancy, with two embryos and one embryo in the left and right horns, respectively. At day 4 of pregnancy, IL- 1ra down-regulated alpha4 mRNA with use of the polymerase chain reaction. Immunohistochemistry showed a decrease of alpha4, alpha v, and beta3, and transmission electron microscopy revealed inhibition of transformation of the plasma membrane. Impairment of embryonic adhesion with IL-1ra is mediated through a direct effect on transformation of the epithelial plasma membrane at the time of implantation as a result of down-regulation of alpha4, alpha v, and beta3.

  8. 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.

  9. Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis.

    Science.gov (United States)

    de Souza, L J; Sampietre, S N; Assis, R S; Knowles, C H; Leite, K R; Jancar, S; Monteiro Cunha, J E; Machado, M C

    2001-01-01

    Bacterial translocation is an important source of pancreas infection in acute pancreatitis. The effect of platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis has been proved in various studies. The aim of this study was to determine whether potent PAF antagonists influence bacterial translocation in acute pancreatitis. Acute pancreatitis was induced in 62 Wistar rats by injection of 2.5% sodium taurocholate into the biliopancreatic duct. The rats treated with PAF factor antagonists received intravenous injection of WEB-2170 (10 mg/kg), lexipafant (5 mg/kg), and BN-52021 (5 mg/kg) 30 minutes before induction of acute pancreatitis. Six hours after induction of acute pancreatitis, bacteriologic cultures and histologic scoring of tissues were performed. There was a statistically significant reduction in bacterial translocation to the mesenteric lymph nodes and liver but not to the pancreas of the rats treated with PAF antagonists. No significant increase in the intestinal bacterial population of any group was found. There were no statistical differences between the pancreatic histologic scores of the groups. PAF antagonists reduced bacterial translocation to distant sites other than the pancreas, preventing the bacterial dissemination that occurs in the early phase of acute pancreatitis and may have beneficial effects on the evolution of this disease.

  10. Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

    Science.gov (United States)

    Morita, Hiroki; Mochiki, Erito; Takahashi, Nobuyuki; Kawamura, Kiyoshi; Watanabe, Akira; Sutou, Toshinaga; Ogawa, Atsushi; Yanai, Mitsuhiro; Ogata, Kyoichi; Fujii, Takaaki; Ohno, Tetsuro; Tsutsumi, Souichi; Asao, Takayuki; Kuwano, Hiroyuki

    2013-01-01

    AIM: To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. METHODS: Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. RESULTS: 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. CONCLUSION: The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. PMID:24151388

  11. Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

    Science.gov (United States)

    Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

    2017-04-14

    Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Adaptations in antagonist co-activation: Role in the repeated-bout effect.

    Directory of Open Access Journals (Sweden)

    Robert E Hight

    Full Text Available Eccentric exercise results in an adaptation which attenuates muscle damage from subsequent exercise-termed the "repeated-bout effect (RBE."Study examined antagonist co-activation and motor-unit recruitment strategy, assessed via dEMG, concomitant to the RBE.Nine participants performed 5 sub-maximal isometric trapezoid (ramp-up, hold, ramp-down contractions at force levels corresponding to 50% and 80% of maximal isometric strength (MVC. Surface EMG signals of the biceps brachii were decomposed into individual motor-unit action potential trains. The relationship between mean firing rate (MFR of each motor-unit and its recruitment threshold (RT was examined using linear regression. Eccentric exercise was then performed until biceps brachii MVC had decreased by ~40%. Surface EMG of the biceps and triceps were collected during eccentric exercise. MVC, range-of-motion (ROM, and delayed onset muscle soreness (DOMS were measured 24-hours, 72-hours, and 1-week following eccentric exercise. Three weeks later all procedures were repeated.Changes in MVC (-32±14% vs -25±10%; p = 0.034, ROM (-11% vs 6%; p = 0.01, and DOMS (31.0±19mm vs 19±12mm; p = 0.015 were attenuated following the second bout of exercise. Triceps EMG was reduced (16.8±9.5% vs. 12.6±7.2%; p = 0.03 during the second bout of eccentric exercise. The slope (-0.60±0.13 vs -0.70±0.18; p = 0.029 and y-intercept (46.5±8.3 vs 53.3±8.8; p = 0.020 of the MFR vs. RT relationship was altered during contractions at 80% of MVC prior to the second bout of eccentric exercise. No changes were observed at 50% of MVC.A reduction in antagonist co-activation during the second bout of eccentric exercise suggests less total force was required to move an identical external load. This finding is supported by the increased negative slope coefficient and an increased y-intercept of the linear relationship between RT and MFR.

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

    Directory of Open Access Journals (Sweden)

    Nooshin Masoudian

    2015-04-01

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

  14. Quantitative ARG microimaging studies of two muscarinic antagonist isomers: Blocking and the effects of cocaine

    Energy Technology Data Exchange (ETDEWEB)

    Som, P.; Wang, G.J.; Oster, Z.H. [Oak Ridge National Lab., TN (United States)] [and others

    1994-05-01

    The distribution of the racemic mixture of IQNP(1-Azabicyclo [2-2-2] oct-3-yl alpha-hydroxy-alpha-(1-iodo-propen-3-yl)-alpha-phenylacetate), a muscarinic antagonist was described earlier. Recently, the radioiodinated Z and E-(R,R) IQNP isomers have been prepared. Quantitative ARG studies using the Z and E isomers were performed in control rats and after pretreatment with ({plus_minus}) QNB or cocaine. High uptake of (Z)-IQNP was seen in the heart and brain with GI and urinary excretion. Lung uptake was lower than with the racemic IQNP. (Z)-IQNP uptake was maximal at 15 min p.i. with homogeneous distribution in the heart. In the brain, highest uptake was in the caudate, cortex, hippocampus, pons and thalamus. (Z)-IQNP showed higher cerebellar uptake and lower cortical uptake compared to (E)-IQNP. Clearance from brain was slower than bean. Heart and brain uptake of (E)-IQNP were markedly lower than the Z isomer. After QNB pretreatment, almost complete blocking of (Z)-IQNP uptake in heart and brain occurred. Cocaine did not significantly affect the distribution of IQNP. These data indicate that (Z)-IQNP has high affinity for the M2 muscarinic receptor with potential for brain and heart imaging. Cocaine appears to have little effect on the muscarinic-cholinergic receptors in the brain and heart.

  15. The antagonistic effect of Banana bunchy top virus multifunctional protein B4 against Fusarium oxysporum.

    Science.gov (United States)

    Zhuang, Jun; Coates, Christopher J; Mao, Qianzhuo; Wu, Zujian; Xie, Lianhui

    2016-06-01

    The viral-induced banana bunchy top disease and the fungal-induced banana blight are two major causes of concern for industrial scale production of bananas. Banana blight is particularly troublesome, affecting ∼80% of crops worldwide. Strict guidelines and protocols are in place in order to ameliorate the effects of this devastating disease, yet little success has been achieved. From the data presented here, we have found that Banana bunchy top virus (BBTV)-infected bananas are more resistant to Fusarium oxysporum f. sp. cubense (Foc). BBTV appears to be antagonistic towards Foc, thus improving the survivability of plants against blight. The BBTV suppressor of RNA silencing, namely protein B4, displays fungicidal properties in vitro. Furthermore, transgenic tomatoes expressing green fluorescent protein (GFP)-tagged protein B4 demonstrate enhanced resistance to F. oxysporum f. sp. lycopersici (Fol). Differential gene expression analysis indicates that increased numbers of photogenesis-related gene transcripts are present in dark-green leaves of B4-GFP-modified tomato plants relative to those found in WT plants. Conversely, the transcript abundance of immunity-related genes is substantially lower in transgenic tomatoes compared with WT plants, suggesting that plant defences may be influenced by protein B4. This viral-fungal interaction provides new insights into microbial community dynamics within a single host and has potential commercial value for the breeding of transgenic resistance to Fusarium-related blight/wilt. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  16. Effect of the Soluble TNF‐Antagonist Etanercept on Tumor Necrosis Factor Bioactivity and Stability

    Science.gov (United States)

    Mann, Douglas L.; Bozkurt, Biykem; Torre‐Amione, Guillermo; Soran, Ozlem Z.; Sivasubramanian, Natarajan

    2008-01-01

    Abstract Background: Targeted anti‐tumor necrosis factor (TNF) strategies in patients with rheumatoid arthritis have resulted in new and/or worsening heart failure in individuals who were free of cardiovascular disease. Methods and Results: To determine the mechanism of new and/or worsening heart failure in patients who were receiving the soluble TNF‐antagonist etanercept, we analyzed frozen plasma samples from a previous clinical trial with etanercept in heart failure patients, and conducted complimentary mechanistic in vitro studies. Analysis of the clinical trial data showed that use of etanercept resulted in a significant 70‐fold increase in the level of immunoreactive TNF. Complimentary in vitro studies using an L929 bioassay showed that at low concentrations of etanercept relative to TNF there was an unexpected 1.5‐ to 1.75‐fold increase in the absolute level of TNF bioactivity. We also examined the effect of etanercept on TNF stability and the results showed that there was a two‐fold increase in the mass of bioactive homotrimeric TNF when the molar ratio of TNF to etanercept was approximately 200:1. Conclusion: Etanercept increases the immunoreactive mass of TNF in heart failure patients, as well as augments TNF cytotoxicity in certain settings, thus suggesting one potential mechanism for the worsening heart failure in some patients who were receiving this agent. PMID:20443835

  17. Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects

    Directory of Open Access Journals (Sweden)

    Krumsiek Jan

    2010-04-01

    Full Text Available Abstract Background MicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms. About 37% of mammalian microRNAs appear to be located within introns of protein coding genes, linking their expression to the promoter-driven regulation of the host gene. In our study we investigate this linkage towards a relationship beyond transcriptional co-regulation. Results Using measures based on both annotation and experimental data, we show that intronic microRNAs tend to support their host genes by regulation of target gene expression with significantly correlated expression patterns. We used expression data of three differentiating cell types and compared gene expression profiles of host and target genes. Many microRNA target genes show expression patterns significantly correlated with the expressions of the microRNA host genes. By calculating functional similarities between host and predicted microRNA target genes based on GO annotations, we confirm that many microRNAs link host and target gene activity in an either synergistic or antagonistic manner. Conclusions These two regulatory effects may result from fine tuning of target gene expression functionally related to the host or knock-down of remaining opponent target gene expression. This finding allows to extend the common practice of mapping large scale gene expression data to protein associated genes with functionality of co-expressed intronic microRNAs.

  18. Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats.

    Science.gov (United States)

    Yayla, Muhammed; Halici, Zekai; Unal, Bunyami; Bayir, Yasin; Akpinar, Erol; Gocer, Fatma

    2014-03-05

    Paracetamol is one of the first rank drugs which cause hepatic damage during drug intoxications. Endothelin (ET) which is known as one of the most potent vasoactive agent has been shown to contribute in the pathophysiology of various diseases. We hypothesized that bosentan, which is a non-selective ET-1 receptor antagonist, can prevent liver damage. This study included 49 female rats. Groups; I: Healthy group, II: Paracetamol (2 g/kg orally). Groups 3, 4 and 5 received NAC 140 mg/kg (2 doses), BOS 45 mg/kg and BOS 90 mg/kg orally, respectively. 1 h after administration of pretreatment drugs, Groups 3, 4, 5 were given paracetamol. VI: received BOS 90 mg/kg. VII: received 140 mg/kg NAC (2 doses). According to biochemical results, TNF-α, ALT and AST levels were statistically increased in the paracetamol group, these parameters were improved in the bosentan groups. Paracetamol administration decreased SOD activity, GSH level and increased level of MDA in the liver, while bosentan administration significantly improved these parameters. In immunohistochemical staining ET-1 receptor expression was excessively increased in paracetamol group, but not in bosentan groups when compared to healthy control. All these results suggest that bosentan exerted protective effects against experimentally induced paracetamol toxicity in liver.

  19. Effect of Hesperidin With and Without a Calcium (Calcilock) Supplement on Bone Health in Postmenopausal Women.

    Science.gov (United States)

    Martin, Berdine R; McCabe, George P; McCabe, Linda; Jackson, George S; Horcajada, Marie Noelle; Offord-Cavin, Elizabeth; Peacock, Munro; Weaver, Connie M

    2016-03-01

    Citrus fruits contain unique flavanones. One of the most abundant of the flavanones, hesperidin, has been shown to prevent bone loss in ovariectomized rats. The objective of the study was to measure the effect of hesperidin with or without calcium supplementation on bone calcium retention in postmenopausal women. The study was a double-blind, placebo-controlled, randomized-order crossover design of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Bone calcium retention was determined from urinary excretion of the rare isotope, (41)Ca, from bone. Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (P hesperidin, is effective at preserving bone in postmenopausal women.

  20. VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Szema Anthony M

    2011-10-01

    Full Text Available Abstract Background Pulmonary Arterial Hypertension (PAH remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1 Can VIP protect against PH in other experimental models? and 2 Does combining VIP with an endothelin (ET receptor antagonist bosentan enhance its efficacy? Methods Within 3 weeks of a single injection of monocrotaline (MCT, s.c. in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o. alone, with VIP (i.p. alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival. Results Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days. Conclusions 1 VIP completely prevented and significantly reversed MCT-induced PAH; 2 VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3 combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway.

  1. 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.

  2. 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

  3. Effects of calcium and humic acid treatment on the growth and ...

    African Journals Online (AJOL)

    Humic acid (HA) may facilitate plant growth by improving the nutrient uptake as well as through hormonal effects. Studies were conducted to investigate the effect of a mixture of calcium and HA on Oriental lily, which is sensitive to calcium deficiency. Two levels of Ca (3.5 and 7.0 meq/L) were combined with 500 mg/L HA ...

  4. 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

  5. Intracerebroventricular application of competitive and non-competitive NMDA antagonists induce similar effects upon rat hippocampal electroencephalogram and local cerebral glucose utilization

    NARCIS (Netherlands)

    Boddeke, H.W.G.M.; Wiederhold, K.H.; Palacios, J.M.

    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

  6. Effects of somatostatin on intestinal calcium transport in the rat.

    Science.gov (United States)

    Favus, M J; Berelowitz, M; Coe, F L

    1981-09-01

    The addition of somatostatin (SRIF) to rat descending colon in vitro increased the calcium secretory flux from serosa to mucosa (Js leads to m) and reduced tissue short-circuit current (Isc) but did not alter the absorptive flux from mucosa to serosa (Js leads to m). Js leads to m increased by 37% at 10(-9) M SRIF and by 48% at 10(-6) M. The response to SRIF was not altered by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and SRIF did not interfere with stimulation of calcium Jm leads to s by 1,25(OH)2D3. Removal of sodium from the buffer abolished the stimulation of Js leads to m by SRIF without reducing basal Js leads to m. Secretory fluxes of mannitol and calcium were strongly correlated in the presence and absence of SRIF, suggesting that SRIF stimulates a paracellular transepithelial pathway for calcium. In the duodenum, SRIF altered neither calcium Js leads to m nor Isc. In the ileum, calcium Js leads to m increased and Isc decreased, as in the colon, but only by 28 and 12%, respectively. The maximal change in calcium Js leads to m caused by SRIF in these three intestinal segments was negatively correlated with the tissue concentration of immunoreactive SRIF. These results suggest that intestinal calcium secretion could, in part, be regulated by intestinal SRIF.

  7. 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

    2015-09-05

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Pharmacokinetic/pharmaco-dynamic modelling and simulation of the effects of different cannabinoid receptor type 1 antagonists on Δ(9)-tetrahydrocannabinol challenge tests.

    Science.gov (United States)

    Guan, Zheng; Klumpers, Linda E; Oyetayo, Olubukayo-Opeyemi; Heuberger, Jules; van Gerven, Joop M A; Stevens, Jasper

    2016-04-01

    The severe psychiatric side effects of cannabinoid receptor type 1 (CB1 ) antagonists hampered their wide development but this might be overcome by careful management of drug development with pharmacokinetic/pharmacodynamic (PK/PD) analyses. PK/PD models suitable for direct comparison of different CB1 antagonists in Δ(9) -tetrahydrocannabinol (THC) challenge tests in healthy volunteer were constructed. The pharmacokinetic models of THC and four CB1 antagonists were built separately. THC-induced effects on heart rate and the visual analogue scale of feeling high in healthy volunteers and inhibitive effects of CB1 antagonists on THC-induced effects were modelled in PD models linked to the PK models. Simulations were then applied to evaluate the reduction rate of each antagonist on the reversal of the THC-induced effect in a unified simulation scenario. The final PK model of THC and antagonists was a two compartment model. An Emax model and logistic regression model were used for effect measures and the antagonist effect was added in these models in a competitive binding manner. t1/2ke0 ranged from 0.00462 to 63.7 h for heart rate and from 0.964 to 150 h for VAS. IC50 ranged from 6.42 to 202 ng ml(-1) for heart rate and from 12.1 to 376 ng ml(-1) for VAS. Benchmark simulation showed different dose-efficacy profiles of two efficacy measures for each CB1 antagonist. PK/PD modelling and simulation approach was suitable for describing and predicting heart rate and feeling high for CB1 antagonists in THC challenge tests. Direct comparison of four antagonists based on simulated efficacy profiles might be of benefit to guide future studies. © 2015 The British Pharmacological Society.

  9. Effects of calcium intake on the cardiovascular system in postmenopausal women.

    Science.gov (United States)

    Challoumas, D; Cobbold, C; Dimitrakakis, G

    2013-11-01

    The use of calcium supplements for the prevention of complications of osteoporosis has significantly increased during the last years. The effects of calcium intake in postmenopausal women on cardiovascular parameters such as blood pressure, serum lipids and cardiovascular events are controversial. Even though transient beneficial effects of calcium supplementation have been reported, especially in women with low dietary calcium intake, their long-term outcomes are inconclusive. Only a very few studies investigating serum lipids in postmenopausal women have been described and these showed significant increases in high-density lipoprotein and high-density lipoprotein to low-density lipoprotein ratio. With regards to cardiovascular events in this population group adverse effects have been reported on the rates of myocardial infarction and stroke with increased calcium intake by some authors, however, others described no effects or even beneficial outcomes. We present a review of the current literature which provides a balanced summary of the possible beneficial and adverse effects of calcium intake in postmenopausal women on cardiovascular parameters. Taking into account the modest effect of calcium supplementation in reducing fracture rates, a reassessment of the role, benefits and adverse effects of calcium supplements should be conducted in postmenopausal women. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Effect of calcium in brine on salt diffusion and water distribution of Mozzarella cheese during brining.

    Science.gov (United States)

    Luo, J; Pan, T; Guo, H Y; Ren, F Z

    2013-02-01

    A soft, pasty, high-moisture surface defect occurs with progressive brining of Mozzarella cheese. Addition of calcium is traditionally used to prevent this defect but the underlying mechanism is not clear. Mozzarella cheese was formed into a cylinder inside brine on its plane surface to ensure semi-infinite, unidirectional mass transfer and placed into brine containing 0, 0.1, or 0.25% (wt/wt) calcium chloride. To monitor the effect on cheese composition of calcium in brine, we measured calcium and water contents of the cheese during brining. The extent of calcium loss from the cheese decreased significantly with the addition of calcium. Addition of calcium to a final concentration of 0.25% decreased the loss of calcium from 94.13 to 18.22% from the outside region of the cheese after 30 d, and the water content of the cheese was decreased from 67.8 to 48.8%. To further elucidate the effect of calcium in brine, the Boltzmann method was used to determine the effective diffusion coefficient value, and low-field nuclear magnetic resonance was used to measure the cheese transversal relaxation time. The migration of calcium interfered with salt diffusion. At the end of brining, the amount of water bound to the protein of the cheese significantly increased. Addition of calcium to a final concentration of 0.25% diminished the proportion of bound water by 20.96%. In conclusion, addition of calcium hinders the diffusion of sodium and modifies the distribution of water in Mozzarella cheese during brining. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Effects of Static and Dynamic Stretching on the Isokinetic Peak Torques and Electromyographic Activities of the Antagonist Muscles.

    Science.gov (United States)

    Serefoglu, Abdullah; Sekir, Ufuk; Gür, Hakan; Akova, Bedrettin

    2017-03-01

    The aim of this study was to investigate if static and dynamic stretching exercises of the knee muscles (quadriceps and hamstring muscles) have any effects on concentric and eccentric isokinetic peak torques and electromyographic amplitudes (EMG) of the antagonist muscles. Twenty healthy male athletes (age between 18-30 years) voluntarily participated in this study. All of the subjects visited the laboratory to complete the following intervention in a randomized order on 5 separate days; (a) non-stretching (control), (b) static stretching of the quadriceps muscles, (c) static stretching of the hamstring muscles, (d) dynamic stretching of the quadriceps muscles, and (e) dynamic stretching of the hamstring muscles. Static stretching exercises either for the quadriceps or the hamstring muscles were carried out at the standing and sitting positions. Subjects performed four successive repetitions of each stretching exercises for 30 seconds in both stretching positions. Similar to static stretching exercises two different stretching modes were designed for dynamic stretching exercises. Concentric and eccentric isokinetic peak torque for the non-stretched antagonist quadriceps or hamstring muscles at angular velocities of 60°/sec and 240°/sec and their concurrent electromyographic (EMG) activities were measured before and immediately after the intervention. Isokinetic peak torques of the non-stretched agonist hamstring and quadriceps muscles did not represent any significant (p > 0.05) differences following static and dynamic stretching of the antagonist quadriceps and hamstring muscles, respectively. Similarly, the EMG activities of the agonist muscles exhibited no significant alterations (p > 0.05) following both stretching exercises of the antagonist muscles. According to the results of the present study it is possible to state that antagonist stretching exercises either in the static or dynamic modes do not affect the isokinetic peak torques and the EMG activities

  12. 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...

  13. The effect of calcium on the properties of charged phospholipid bilayers

    DEFF Research Database (Denmark)

    Pedersen, U.R.; Leidy, Chad; Westh, P.

    2006-01-01

    to sodium ions, calcium ions are localised in a narrow (∼ 10 Å) band around the phosphate group. The interaction of calcium with the lipid molecules enhances the molecular packing of the PG and PS lipids. This observation is in good agreement with emission spectra of the membrane partitioning probe Laurdan......-myristoyl-phosphatidyl-serine (DMPS) bilayers as well as a protonated di-myristoyl-phosphatidyl-serine (DMPSH) bilayer. We were particularly interested in calcium ions due to their important role in biological systems. Simulations performed in the presence of calcium ions (DMPG, DMPS) or sodium ions (DMPS) were run for 45–60 ns...... affected by the counterions, where calcium ions have a more pronounced effect than sodium ions. Calcium ions were found to be tightly bound to the anionic groups of the lipid molecules and as such appear to constitute an integral part of the membrane interface on nanoseconds time scales. In contrast...

  14. Effects of Urotensin II and Its Specific Receptor Antagonist Urantide on Rat Vascular Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Juan Zhao

    2013-05-01

    Full Text Available We investigated the effects of urantide, a receptor antagonist of urotensin II (U-II, on the expression of U-II and its receptor GPR14 in rat vascular smooth muscle cells. Vascular smooth muscle cells from rat thoracic aorta were cultured by explant method. Subjects in this experiment were divided into eight groups: normal control group (group C, U-II group (group M, positive control group (Flu group and urantide-treated groups (10-10, 10-9, 10-8, 10-7 and 10-6 mol/L. Cultured vascular smooth muscle cells in vitro were studied by immunocytochemistry, biochemistry, and flow cytometry. U-II (10-8 mol/L promoted the proliferation of vascular smooth muscle cells at each time point, influenced cell cycle, increased proliferation index and S-phase cell fraction, and dramatically promoted the expression of U-II and GPR14. In the concentration range from 10-10 to 10-6 mol/L, urantide dramatically inhibited the proliferation of vascular smooth muscle cells and the protein expression of U-II and GPR14, especially at a concentration of 10-6 mol/L. U-II, binding with its receptor GPR14, promotes vascular smooth muscle cells proliferation and migration, which can be inhibited by urantide. This study provides an evidence for understanding the effects of U-II and its receptor GPR14 on vascular smooth muscle cells.

  15. Effect of an oxytocin receptor antagonist (atosiban) on uterine electrical activity.

    Science.gov (United States)

    Hadar, Eran; Melamed, Nir; Aviram, Amir; Raban, Oded; Saltzer, Liat; Hiersch, Liran; Yogev, Yariv

    2013-10-01

    The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery. Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus. Uterine activity was recorded with a noninvasive, 9-channel recorder with an electromyography amplifier and a 3-dimensional position sensor with an automatic data analyzer. Uterine electrical activity was quantified by an electrical uterine monitor (EUM) and measured in microwatts per second (μW/s). The overall pre-Tractocile EUM index was 3.43 ± 0.58 μW/s, which was significantly higher than baseline uterine activity in women without preterm contractions (2.3 ± 0.11 μW/s; P = .001). During the administration of Tractocile, the EUM index gradually decreased in a relatively constant rate from 3.43 ± 0.58 μW/s to 2.56 ± 0.88 μW/s after 330 minutes of continuous therapy (P uterine electrical activity in women with preterm labor. This information can provide more insight into the effects of tocolytic agents and to aid in the risk stratification of preterm delivery in women with preterm contractions. Copyright © 2013 Mosby, Inc. All rights reserved.

  16. 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

  17. 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.

  18. Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

    Science.gov (United States)

    Bauerfeind, P; Cilluffo, T; Fimmel, C J; Emde, C; von Ritter, C; Kohler, W; Gugler, R; Gasser, T; Blum, A L

    1987-05-01

    The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300 mg nocte. Tablets were taken at 2115 and 0900 h. Smokers smoked a cigarette hourly from 0700 to 2300 h. Breakfast, lunch, and dinner were standardised. Intragastric acidity was measured with a combined intragastric glass electrode and a solid state recorder. The subjects were fully ambulatory. The three histamine H2-receptor antagonist regimens were less effective (p = 0.04) in smokers than in non-smokers, but the difference between acidity of smokers and non-smokers was small. Means of medians of pH during a 24-h period with placebo, cimetidine 800 mg, ranitidine 2 X 150 mg and ranitidine 300 mg were 1.6, 2.3, 3.1, and 2.7 in smokers and 1.5, 2.7, 3.2, and 3.1 in non-smokers, respectively. In a second part of the study seven chronic smokers were reexamined after acutely stopping smoking: inhibition of gastric acidity by histamine H2-receptor antagonists was similar before and after withdrawal. Smoking does not affect intragastric acidity in untreated volunteers and only slightly decreases the effectiveness of histamine H2-receptor antagonists on intragastric acidity. This effect best in part explains the unfavourable effect of smoking on healing of peptic ulcer in patients treated with these drugs.

  19. Effects of pyrimidine antagonists on sialic acid regeneration in HL-60 cells.

    Science.gov (United States)

    Hindenburg, A A; Taub, R N; Grant, S; Chang, G; Baker, M A

    1985-07-01

    Because alterations in cell membrane sialoglycoconjugates can affect the behavior of neoplastic cells, we investigated the effects of in vitro treatment with antimetabolites used in cancer therapy on the expression of membrane sialic acid in cultured HL-60 leukemic cells. In these studies, cells were incubated with Vibrio cholerae neuraminidase to remove surface sialic acid. Reappearance of membrane sialic acid during drug treatment was followed (a) by measuring changes in radioactive surface labeling of viable cells with sodium metaperiodate-sodium[3H]-borohydride, (b) by measuring the decline in accessible surface galactosyl receptor sites which occurred coincident with membrane sialic acid replacement, and (c) by measuring the incorporation of [3H]glucosamine into membrane-associated neuraminidase-labile sialic acid. We were especially interested in learning whether drugs that affect intracellular pools of cytidine triphosphate (CTP), an important nucleotide intermediate in sialylation reactions, could inhibit regeneration of membrane sialic acid. 3-Deazauridine, a competitive inhibitor of CTP synthetase, depleted CTP pools and curtailed surface membrane resialylation with little or no effect on synthesis of de novo sialic acid from precursor sugars. The addition of cytidine restored CTP pools and sialic acid regeneration. Acivicin, a glutamine antagonist, also depleted CTP pools and curtailed surface membrane resialylation. In addition, it retarded de novo synthesis of sialic acid. The addition of cytidine restored intracellular CTP pools and sialic acid regeneration. However, both cytidine and guanosine were required to restore sialic acid synthesis from precursor sugars. 1-beta-D-Arabinofuranosylcytosine, a competitive inhibitor of sialic acid synthetase and of sialyltransferase, inhibited both de novo sialic acid synthesis and membrane resialylation. Only the latter effect was reversed by the addition of exogenous cytidine. Hydroxyurea, an agent shown

  20. [Antioxidative effects of cysteinyl leukotriene receptor antagonists montelukast and HAMI 3379 on ischemic injury in rat cortical neurons in vitro].

    Science.gov (United States)

    Xu, Dong-min; Zhang, Xia-yan; Wang, Xiao-rong; Chen, Lu; Zhang, Li-hui; Shi, Qiao-juan; Fang, San-hua; Lu, Yun-bi; Zhang, Wei-ping; Wei, Er-qing

    2014-05-01

    To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro. Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R)or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2R,and the effects were observed. ROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1μmol/L moderately decreased OGD/R-induced ROS production (PMontelukast mildly attenuated OGD/R-induced MMP depolarization (PMontelukast and HAMI 3379 at 0.1-1μmol/L moderately attenuated H2O2-induced neuronal injury (Pmontelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.

  1. The effects of calcium dobesilate on the mechanical function of rat hearts.

    Science.gov (United States)

    Cihan Ozbek, I; Arslan, C; Cantürk, E; Süzer, O

    2009-06-01

    Calcium dobesilate is an angio-protective agent that has positive effects on hemorheological parameters. It decreases blood and plasma viscosity, thrombocyte aggregation, and microvascular hyperpermeability. It is an antioxidant that increases endothelial-derived vasodilator substance secretion. In this experimental study, the effects of calcium dobesilate on myocardial ischemia reperfusion injury were investigated. Using the Langendorff setup, 24 adult Wistar albino rat hearts were perfused. MeanP (mean pressure perfusing the coronary arteries), PSP (maximum left ventricle pressure), +dp/dt(max) (change in contraction power over time), -dp/dt(max) (change in relaxing power over time), PP (peak systolic pressure-minimum balloon pressure) and bpm (number of heart beats per minute) were evaluated. The control group (N.=6) was perfused with Tyrode solution alone. The other three groups (N.=6 for each group) were perfused with the Tyrode solution and calcium dobesilate either before ischemia, during the ischemia reperfusion period, or during the reperfusion-only period. The meanP values were significantly higher in groups perfused by calcium dobesilate. For other parameters, calcium dobesilate did not demonstrate a positive effect. This study showed that calcium dobesilate may have cardio-protective effects in isolated, perfused rat hearts. In hearts perfused by calcium dobesilate, the increase in mean P may be explained by the increase in endothelium-derived vasodilator substances. Further studies are needed to better characterize the myocardial protective effects of calcium dobesilate.

  2. Effects of a thromboxane receptor antagonist on prostaglandin D2 and histamine induced bronchoconstriction in man.

    Science.gov (United States)

    al Jarad, N; Hui, K P; Barnes, N

    1994-01-01

    Many prostanoids including are prostaglandin (PG) F2 alpha and PGD2 are potent bronchoconstrictor agents. There is evidence to suggest that airway thromboxane (TP) receptor may act as a common receptor for their bronchoconstrictor actions. We tested the hypothesis that inhaled prostaglandin (PG) D2-induced bronchoconstriction is mediated by interacting with the TP receptor antagonist, ICI 192605, on the bronchoconstrictor response to inhaled PGD2 in a double-blind, placebo-controlled and crossed-over trial in normal subjects. The effect of ICI 192605 on histamine induced bronchoconstriction served as control for non-specific bronchodilatory actions. The study had two phases; the first consisted of two inhaled PGD2 challenge study days, and the second phase was that of inhaled histamine. Each study day was separated by at least a week. On each study day, the challenge tests were carried out 30 min after ingestion of 100 mg ICI 192605 or placebo. Doubling concentrations of agonist were given till more than 35% fall in post-diluent specific airway conductance (sGaw) occurred. The concentration needed to cause a fall in a sGaw of 35% post-diluent value (PC35sGaw) was then determined from linear interpolation of the log dose-response. Eight male subjects (median age 26, range 20-35 years) completed the study. ICI 192605 did not change baseline airway calibre 30 min after ingestion on either PGD2 or histamine study days. ICI 192605 significantly shifted the dose-response curve to inhaled PGD2 to the right by a median of 3.4 fold (Wilcoxon rank sign test, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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.

  4. 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...

  5. 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

    ; 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 reversible...

  6. 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...

  7. Is the use of a GnRH antagonist effective in patients with polycystic ...

    African Journals Online (AJOL)

    offered controlled ovarian stimulation (COS) and in vitro fertilisation (IVF) technology. Aim. The aim of this study was to assess whether there was a difference in the pregnancy outcomes of women with PCOS when a standard gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) protocol was used for ovarian ...

  8. 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 ...

  9. Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist ...

    African Journals Online (AJOL)

    Purpose: To evaluate lymphatic system targeting and inhibitory ability of N15P nano-liposomal preparation (naLipo-N15P) of CXCR4 receptor antagonist in HIV infection. Methods: Chemotactic and chemotaxic inhibition activity assays were used to analyze the biological activity of naLipo-N15P. The anti-HIV potential of ...

  10. Regulation of structural plasticity and neurogenesis during stress and diabetes; protective effects of glucocorticoid receptor antagonists

    NARCIS (Netherlands)

    Lucassen, P.J.; Fitzsimons, C.P.; Vreugdenhil, E.; Hu, P.; Oomen, C.; Revsin, Y.; Joëls, M.; de Kloet, E.R.; Gravanis, A.G.; Mellon, S.H.

    2011-01-01

    In this chapter, we will review changes in structural plasticity of the adult hippocampus during stress and exposure to glucocorticoids (GCs). We further discuss the protective and normalizing role of glucocorticoid receptor (GR) antagonist treatment under these conditions and its implications for

  11. Calcium carbide (CaC2): Effect on fruit set and yield of mango ...

    African Journals Online (AJOL)

    Calcium carbide (CaC2): Effect on fruit set and yield of mango ( Mangifera indica L.) cv. ... photosynthetic rate, final fruit drop, yield per plant, fruit weight, fruit volume, pulp weight, peel weight, juice weight and fruit skin color were significantly affected by the calcium carbide treatment while number of new flushes per branch, ...

  12. Influence of endothelium on the membrane-stabilizing effect of calcium

    African Journals Online (AJOL)

    Dr Olaleye

    ABSTRACT. Background: A decrease in membrane permeability to calcium ions, caused by increased extracellular calcium concentration is referred to as membrane-stabilization. There is a paucity of information on the role of vascular endothelium in the membrane-stabilizing effect of Ca2+ ions. The goal of the present ...

  13. Effects of Physical Training and Calcium Intake on Bone Mineral Density of Students with Mental Retardation

    Science.gov (United States)

    Hemayattalab, Rasool

    2010-01-01

    The purpose of this study was to investigate the effects of physical training and calcium intake on bone mineral density (BMD) of students with mental retardation. Forty mentally retarded boys (age 7-10 years old) were randomly assigned to four groups (no differences in age, BMD, calcium intake and physical activity): training groups with or…

  14. Metabolomic assessment reveals a stimulatory effect of calcium treatment on glucosinolates contents in broccoli microgreen

    Science.gov (United States)

    Preharvest calcium application has been shown to increase broccoli microgreen yield and extend shelf life. Here we investigated the effect of calcium application on its metabolome using ultra high-performance liquid chromatography (UHPLC) tandem with mass spectrometry (HRMS). The data collected were...

  15. Effects of pre- and postharvest calcium treatments on shelf life and postharvest quality of broccoli microgreens

    Science.gov (United States)

    Microgreens’ extremely short shelf life limits their commercial usage. The objective of this study is to compare the effect of pre- and post- harvest treatments using different forms of calcium on the postharvest quality and shelf-life of broccoli microgreens. Preharvest spray with calcium lactate, ...

  16. 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.

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

    Science.gov (United States)

    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

    2014-09-22

    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 architecture and quantitative electroencephalography (qEEG) spectral profiles across preclinical species. Active-phase dosing of DORA-22 induced consistent effects on sleep architecture in mice, rats, dogs, and rhesus monkeys; attenuation of active wake was accompanied by increases in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Eszopiclone, a representative GABAA receptor modulator, promoted sleep in rats and rhesus monkeys that was marked by REM sleep suppression, but had inconsistent effects in mice and paradoxically promoted wakefulness in dogs. Active-phase treatment of rats with DORA-12 similarly promoted NREM and REM sleep to magnitudes nearly identical to those seen during normal resting-phase sleep following vehicle treatment, whereas eszopiclone suppressed REM even to levels below those seen during the active phase. The qEEG changes induced by DORA-12 in rats also resembled normal resting-phase patterns, whereas eszopiclone induced changes distinct from normal active- or inactive-phase spectra. Co-dosing experiments, as well as studies in transgenic rats lacking orexin neurons, indicated partial overlap in the mechanism of sleep promotion by orexin and GABA modulation with the exception of the REM suppression exclusive to GABAA receptor modulation. Following REM deprivation in mice, eszopiclone further suppressed REM sleep while DORA-22 facilitated recovery including increased REM sleep. DORAs promote NREM and importantly REM sleep that is similar in

  18. Effect of hypokinesia on calcium loss in calcium-supplemented and -unsupplemented rats.

    Science.gov (United States)

    Zorbas, Yan G; Kakuris, Kostas K; Deogenov, Viktor A; Neophitos, Eugenios A

    2008-07-01

    We undertook this study to determine total calcium (Ca(2+)) loss in Ca(2+)-deficient tissue and tissue Ca(2+) loss with and without Ca(2+) supplementation during hypokinesia (HK; diminished movement). Studies were conducted on 240 male Wistar rats during a pre-experimental period of 9 days and an experimental period of 98 days. Rats were equally divided into four groups: unsupplemented vivarium control rats (UVCR), unsupplemented hypokinetic rats (UHKR), supplemented vivarium control rats (SVCR), and supplemented hypokinetic rats (SHKR). Calcium supplementation of 2.6 mmol was given to animals in the SVCR and SHKR groups. Gastrocnemius muscle and right femur bone Ca(2+) level reduced (p vivarium control groups (SVCR and UVCR). Muscle and bone Ca(2+) content decreased more (p <0.05), while plasma Ca(2+) level, and urine and fecal Ca(2+) loss increased more (p <0.05) in the SHKR group than in the UHKR group. Tissue Ca(2+) deficiency during HK is more evident with than without Ca(2+) supplementation and Ca(2+) loss was exacerbated with higher than lower tissue Ca(2+) deficiency. This shows that tissue Ca(2+) deficiency does not result from the lower Ca(2+) content in the food consumed and the total bodily Ca(2+) loss is not caused by the higher tissue Ca(2+) content but due to the impossibility of the body to use Ca(2+) during prolonged HK.

  19. Effect of uncoated calcium carbonate and stearic acid coated ...

    Indian Academy of Sciences (India)

    Administrator

    butylene terephthalate) (PBT)/ ... Calcium carbonate particles, plain and coated with stearic acid, were kindly supplied by 20 MICRONS .... absorbed by the CaCO3 surface thus increasing the tem- perature of the point of maximum degradation ...

  20. Effects of the adenosine A 2A antagonist KW 6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide.

    Science.gov (United States)

    Betz, A J; Vontell, R; Valenta, J; Worden, L; Sink, K S; Font, L; Correa, M; Sager, T N; Salamone, J D

    2009-09-29

    Typical antipsychotic drugs, including haloperidol and pimozide, have been shown to produce parkinsonian motor effects such as akinesia and tremor. Furthermore, there is an antagonistic interaction between adenosine A(2A) and dopamine D(2) receptors in the basal ganglia, which is important for motor functions related to the production of parkinsonian symptoms. Several experiments were conducted to assess the effects of the selective adenosine A(2A) antagonist KW 6002 on both the motor and cellular effects of subchronic administration of pimozide. The motor test employed was tremulous jaw movements, which is used as a model of parkinsonian tremor. In addition, c-Fos expression in the ventrolateral neostriatum, which is the striatal area most associated with tremulous jaw movements, was used as a marker of striatal cell activity in animals that were tested in the behavioral experiments. Repeated administration of 1.0 mg/kg pimozide induced tremulous jaw movements and increased ventrolateral striatal c-Fos expression, while administration of 20.0 mg/kg of the atypical antipsychotic quetiapine did not. The tremulous jaw movements induced by pimozide were significantly reduced by co-administration of either the adenosine A(2A) antagonist KW 6002 or the muscarinic antagonist tropicamide. Pimozide-induced increases in ventrolateral striatal c-Fos expression were reduced by a behaviorally effective dose of KW 6002, but c-Fos expression in pimozide-treated rats was actually increased by tropicamide. These results indicate that two different drug manipulations that act to reduce tremulous jaw movements can have different effects on DA antagonist-induced c-Fos expression, suggesting that adenosine A(2A) antagonism and muscarinic receptor antagonism exert their motor effects by acting on different striatal circuits.

  1. Effect of extracellular calcium chloride on sporangiospore-yeast ...

    African Journals Online (AJOL)

    To examine this model further, this study evaluated the ability of sporangiospores of Rhizopus stolonifer to undergo morphogenetic transformation in the presence of different levels of extracellular calcium (0.0, 0.20, 0.25, 0.50, 1.0, 1.5 and 1.8 mM). It was found that calcium supported yeast induction and proliferation to ...

  2. The effects of agonist and antagonist muscle activation on the knee extension moment-angle relationship in adults and children.

    Science.gov (United States)

    O'Brien, Thomas D; Reeves, Neil D; Baltzopoulos, Vasilios; Jones, David A; Maganaris, Constantinos N

    2009-08-01

    The present study examined the effect of agonist activation and antagonist co-activation on the shape of the knee extension moment-angle relationship in adults and children. Isometric knee extension maximum voluntary contractions (MVCs) were performed at every 5 degrees of knee flexion between 55 degrees and 90 degrees (full extension = 0 degrees) by ten men, ten women, ten boys and ten girls. For each trial, the knee extensors' voluntary activation level was quantified using magnetic stimulation and the level of antagonist co-activation was quantified from their electromyographical activity. Peak MVC moment was greater for men (264 +/- 63 N m) than women (177 +/- 60 N m), and greater for adults than children (boys 78 +/- 17 N m, girls 91 +/- 28 N m) (p develop and mature into adults the shape of the moment-angle relationship is not altered.

  3. Cardioprotective effect of calcium dobesilate during open-heart surgery.

    Science.gov (United States)

    Iskesen, Ihsan; Saribulbul, Osman; Cerrahoglu, Mustafa; Onur, Ece; Tekin, Cetin; Sirin, Hayrettin

    2006-02-01

    The purpose of this double-blind, controlled, prospective randomized study was to investigate the possible effects of the preoperative use of calcium dobesilate (CLS2210) on the biochemical markers of myocardial injury during open-heart surgery, and to determine if it has any myocardial protective effects. Twenty-four patients undergoing elective cardiac surgery were included in this study and randomized into two groups. CLS2210 was given orally to 12 patients for 14 days before the operation (CD group), but not to the other 12 patients (control group). Serum CK, CK-MB, myoglobin and troponin-T levels were measured from venous blood samples before and after the operation for evaluation of the effect of this drug against myocardial damage. Blood samples were also taken from the radial artery and the coronary sinus before the institution of cardiopulmonary bypass (CPB), and 2 and 15 minutes after the removal of the cross-clamp in order to measure the lactate levels and calculate the lactate extraction of the myocardium. First, CK-MB levels in patients of the CD group were significantly lower than those of the control group (p < 0.05) at the 2nd and 18th postoperative hour. Second, myoglobin and troponin-T levels in the CD group were significantly lower than those of the control group (p < 0.05) at the 2nd, 18th and 48th postoperative hour. Third, there was a significant difference in lactate extraction calculation values between the groups at the 2nd minute after removal of the cross-clamp (p < 0.05). We concluded that preoperative use of CLS2210 has some beneficial effects in protecting the myocardium and decreasing the myocardial injury during the cardioplegic arrest period in open-heart surgery.

  4. Effect of calcium chelators on heat coagulation and heat-induced changes of concentrated micellar casein solutions: The role of calcium-ion activity and micellar integrity

    NARCIS (Netherlands)

    Kort, de E.J.P.; Minor, M.; Snoeren, T.A.L.; Hooijdonk, van A.C.M.; Linden, van der E.

    2012-01-01

    There is general consensus that calcium chelators enhance heat stability in milk. However, they increase the heat stability to considerably different extents. For this reason, the effect of various calcium chelators on heat coagulation and heat-induced changes of concentrated micellar casein

  5. Effect of acid rain on calcium carbonate saturation in the Albemarle sound of North Carolina

    Energy Technology Data Exchange (ETDEWEB)

    Rudolph, K.A.; Burgess, S.K.; Willey, J.D.; Kieber, R.J. [Univ. of North Carolina, Wilmington, NC (United States)

    1996-10-01

    The effects of acidic rainwater additions on calcium carbonate solubility and alkalinity in the poorly buffered, biologically active and commercially important waters of the Albemarle Sound, NC are reported. Samples collected monthly at four sites were analyzed for salinity, pK total alkalinity, and calcium concentrations. Five percent and 10% dilutions of sulfuric acid at pH 4, mimicking acid rain additions, were added and total alkalinity and calcium concentrations again determined. The addition of acid decreased the alkalinity in the Albemarle samples by as much as 15%, although the magnitude of the impact depended both on site and season. The effects of acid additions on dissolved calcium concentrations were more variable,. and also displayed a site and season dependency. Calcium concentrations, alkalinity, and pH values were also determined during controlled laboratory experiments, where 25 mg/L Callinectes sapidus shells were added to Albemarle Sound water. All three analytes increased significantly upon acid additions relative to controls.

  6. Cholesterol-Lowering Effect of Calcium Alginate in Rats.

    Science.gov (United States)

    Idota, Yoko; Kogure, Yumi; Kato, Takako; Ogawa, Mana; Kobayashi, Shoko; Kakinuma, Chihaya; Yano, Kentaro; Arakawa, Hiroshi; Miyajima, Chihiro; Kasahara, Fumiyoshi; Ogihara, Takuo

    2016-01-01

    We examined whether calcium alginate (Ca-Alg) reduces blood cholesterol levels in rats fed a high-cholesterol diet. First, we examined taurocholate adsorption in vitro by various types of sodium alginate (Na-Alg). High molecular-weight, guluronic acid-rich Na-Alg showed the greatest adsorption of taurocholate, and therefore the corresponding Ca-Alg was chosen for the in vivo study. Rats were fed a high-cholesterol diet or a Ca-Alg-containing diet for 2 weeks. Body weight and diet intake were measured, and the general condition of the animals was monitored during this period. After 14 d, the plasma concentration of cholesterol, portal plasma concentration of bile acid, and bile acid in feces were measured. The plasma concentration of cholesterol was significantly reduced in rats fed a 2% Ca-Alg-containing diet. Furthermore, the portal concentration of bile acid was significantly lowered in the 2% Ca-Alg group. A tendency for a Ca-Alg concentration-dependent increase in fecal excretion of bile acid was also seen, although it was not statistically significant. While several changes in biochemical parameters and histopathological findings were observed, all the values remained within the physiological range. These results indicate that Ca-Alg is effective in reducing plasma cholesterol. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which in turn might stimulate bile acid synthesis from cholesterol in the liver, leading to a decrease in plasma cholesterol.

  7. Effects of the AMPA antagonist ZK 200775 on visual function: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Richard Bergholz

    Full Text Available BACKGROUND: ZK 200775 is an antagonist at the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA receptor and had earned attention as a possible neuroprotective agent in cerebral ischemia. Probands receiving the agent within phase I trials reported on an alteration of visual perception. In this trial, the effects of ZK 200775 on the visual system were analyzed in detail. METHODOLOGY: In a randomised controlled trial we examined eyes and vision before and after the intravenous administration of two different doses of ZK 200775 and placebo. There were 3 groups of 6 probands each: Group 1 recieved 0.03 mg/kg/h, group 2 0.75 mg/kg/h of ZK 200775, the control group received 0.9% sodium chloride solution. Probands were healthy males aged between 57 and 69 years. The following methods were applied: clinical examination, visual acuity, ophthalmoscopy, colour vision, rod absolute threshold, central visual field, pattern-reversal visual evoked potentials (pVEP, ON-OFF and full-field electroretinogram (ERG. PRINCIPAL FINDINGS: No effect of ZK 200775 was seen on eye position or motility, stereopsis, pupillary function or central visual field testing. Visual acuity and dark vision deteriorated significantly in both treated groups. Color vision was most remarkably impaired. The dark-adapted ERG revealed a reduction of oscillatory potentials (OP and partly of the a- and b-wave, furthermore an alteration of b-wave morphology and an insignificantly elevated b/a-ratio. Cone-ERG modalities showed decreased amplitudes and delayed implicit times. In the ON-OFF ERG the ON-answer amplitudes increased whereas the peak times of the OFF-answer were reduced. The pattern VEP exhibited lower amplitudes and prolonged peak times. CONCLUSIONS: The AMPA receptor blockade led to a strong impairment of typical OFF-pathway functions like color vision and the cone ERG. On the other hand the ON-pathway as measured by dark vision and the scotopic ERG was affected as well

  8. Effects of the AMPA antagonist ZK 200775 on visual function: a randomized controlled trial.

    Science.gov (United States)

    Bergholz, Richard; Staks, Thomas; Rüther, Klaus

    2010-08-12

    ZK 200775 is an antagonist at the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor and had earned attention as a possible neuroprotective agent in cerebral ischemia. Probands receiving the agent within phase I trials reported on an alteration of visual perception. In this trial, the effects of ZK 200775 on the visual system were analyzed in detail. In a randomised controlled trial we examined eyes and vision before and after the intravenous administration of two different doses of ZK 200775 and placebo. There were 3 groups of 6 probands each: Group 1 recieved 0.03 mg/kg/h, group 2 0.75 mg/kg/h of ZK 200775, the control group received 0.9% sodium chloride solution. Probands were healthy males aged between 57 and 69 years. The following methods were applied: clinical examination, visual acuity, ophthalmoscopy, colour vision, rod absolute threshold, central visual field, pattern-reversal visual evoked potentials (pVEP), ON-OFF and full-field electroretinogram (ERG). No effect of ZK 200775 was seen on eye position or motility, stereopsis, pupillary function or central visual field testing. Visual acuity and dark vision deteriorated significantly in both treated groups. Color vision was most remarkably impaired. The dark-adapted ERG revealed a reduction of oscillatory potentials (OP) and partly of the a- and b-wave, furthermore an alteration of b-wave morphology and an insignificantly elevated b/a-ratio. Cone-ERG modalities showed decreased amplitudes and delayed implicit times. In the ON-OFF ERG the ON-answer amplitudes increased whereas the peak times of the OFF-answer were reduced. The pattern VEP exhibited lower amplitudes and prolonged peak times. The AMPA receptor blockade led to a strong impairment of typical OFF-pathway functions like color vision and the cone ERG. On the other hand the ON-pathway as measured by dark vision and the scotopic ERG was affected as well. This further elucidates the interdependence of both pathways. Clinical

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

    DEFF Research Database (Denmark)

    Bisgaard, H

    2001-01-01

    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...

  10. 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.

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

    Science.gov (United States)

    Kunda, Shailaja; Cheriyan, John; Hur, Michael; Balsara, Rashna D; Castellino, Francis J

    2013-01-01

    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.

  12. Effect of calcium and cholecalciferol supplementation on several parameters of calcium status in plasma and urine of captive Asian (Elephas maximus) and African elephants (Loxodonta africana).

    Science.gov (United States)

    van Sonsbeek, Gerda R; van der Kolk, Johannes H; van Leeuwen, Johannes P T M; Everts, Hendrik; Marais, Johan; Schaftenaar, Willem

    2013-09-01

    The aim of the current study was to assess the effect of oral calcium and cholecalciferol supplementation on several parameters of calcium status in plasma and urine of captive Asian (Elephas maximus; n=10) and African elephants (Loxodonta africana; n=6) and to detect potential species differences. Calcium and cholecalciferol supplementation were investigated in a feeding trial using a crossover design consisting of five periods of 28 days each in summer. From days 28-56 (period 2), elephants were fed the Ca-supplemented diet and from days 84-112, elephants were fed the cholecalciferol-supplemented diet (period 4). The control diet was fed during the other periods and was based on their regular ration, and the study was repeated similarly during winter. Periods 1, 3, and 5 were regarded as washout periods. This study revealed species-specific differences with reference to calcium and cholecalciferol supplementation. Asian elephants showed a significant increase in mean plasma total calcium concentration following calcium supplementation during summer, suggesting summer-associated subclinical hypocalcemia in Western Europe. During winter, no effect was seen after oral calcium supplementation, but a significant increase was seen both in mean plasma, total, and ionized calcium concentrations after cholecalciferol supplementation in Asian elephants. In contrast, evidence of subclinical hypocalcemia could be demonstrated neither in summer nor in winter in African elephants, although 28 days of cholecalciferol supplementation during winter reversed the decrease in plasma 1,25(OH)2-cholecalciferol and was followed by a significant increase in mean plasma total calcium concentration. Preliminary findings indicate that the advisable permanent daily intake for calcium in Asian elephants and cholecalciferol in both elephant species at least during winter might be higher than current guidelines. It is strongly recommended to monitor blood calcium concentrations and, if

  13. 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

  14. 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 ...

  15. Opioid Antagonist Impedes Exposure.

    Science.gov (United States)

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  16. Effects of dietary calcium on Helicobacter pylori-induced gastritis in Mongolian gerbils.

    Science.gov (United States)

    Iimuro, Masaki; Nakamura, Shiro; Arakawa, Tetsuo; Wakabayashi, Keiji; Mutoh, Michihiro

    2013-09-01

    Helicobacter pylori (Hp) infection causes gastritis and is considered a gastric cancer risk factor. We have previously reported that codfish meal markedly enhanced Hp-induced gastritis in Mongolian gerbils. In the present study, we sought the responsible components in codfish meal. Codfish were divided into three parts (meat, viscera and 'other parts', including bone), and administered to Hp-infected gerbils. Subsequently, cod bone, sardine bone and prawn shell were tested, along with major calcium components, hydroxyapatite and calcium carbonate, in bone and shell, respectively. 'Other parts' and cod bone enhanced Hp-induced gastritis, as was observed for whole codfish. Similarly, sardine bone and prawn shell, as well as 0.22-0.88% hydroxyapatite and calcium carbonate, enhanced gastritis. In contrast, administration of a higher dose of the calcium compounds exerted protective effects. Intake of calcium compounds may contribute to enhancement of Hp-induced gastritis.

  17. The effect of fluoride on the serum level of calcium in the rat (Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Fočak M.

    2012-01-01

    Full Text Available The effect of fluoride on the calcium level in serum was analyzed in the laboratory rat Rattus norvegicus. The control group consisted of 10, and the experimental group of 15 animals. In the experimental group, fluoride at a concentration of 3 mg/100 g body weight of rats was intramuscularly injected into the musculus gluteus maximus. The concentration of calcium was measured by the CPC method. The average serum calcium concentration was 2.46 mmol/l, with female rats having higher values of serum calcium than male rats. Fluoride caused the reduction of calcium concentration in serum (p<0.05; the reduction was significantly expressed in female rats (p<0.000.

  18. Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

    Science.gov (United States)

    Wei, Yong; Kong, Xiang Lei; Li, Wen Bin; Wang, Zun Song

    2014-12-01

    This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  19. Effects of calcium source on biochemical properties of microbial CaCO3 precipitation

    Directory of Open Access Journals (Sweden)

    Jing eXu

    2015-12-01

    Full Text Available The biochemical properties of CaCO3 precipitation induced by Sporosarcina pasteurii, an ureolytic type microorganism, were investigated. Effects of calcium source on the precipitation process were examined, since calcium source plays a key role in microbiologically-induced mineralization. Regardless of the calcium source type, three distinct stages in the precipitation process were identified by Ca2+, NH4+, pH and cell density monitoring. Compared with stage 1 and 3, stage 2 was considered as the most critical part since biotic CaCO3 precipitation occurs during this stage. Kinetics studies showed that the microbial CaCO3 precipitation rate for calcium lactate was over twice of that for calcium nitrate, indicating that calcium lactate is more beneficial for the cell activity, which in turn determines urease production and CaCO3 precipitation. X-ray diffraction analysis confirmed the CaCO3 crystal as calcite, although scanning electron microscopy revealed a difference in crystal size and morphology if calcium source was different. The findings of this paper further suggest a promising application of microbiologically-induced CaCO3 precipitation in remediation of surface and cracks of porous media, e.g. cement-based composites, particularly by using organic source of calcium lactate.

  20. 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.

  1. Effects of calcium-fortified ice cream on markers of bone health.

    Science.gov (United States)

    Ferrar, L; van der Hee, R M; Berry, M; Watson, C; Miret, S; Wilkinson, J; Bradburn, M; Eastell, R

    2011-10-01

    Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7 days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1 h of consuming ice cream. Body weight remained constant over 28 days. Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. Eighty women, ages 20-39 years (calcium intake ice cream containing 96, 244, 459 or 676 mg calcium daily for 28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h (n = 29 women). There were significant mean decreases by 7 days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change significantly between baseline and 28 days. Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244 mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women.

  2. 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.

  3. [Acute biochemical effects of calcium: comparison of two dosage forms of calcium carbonate (powder and effervescent tablets) and milk in healthy women].

    Science.gov (United States)

    Zikán, V; Roubal, P; Stĕpán, J

    2002-03-01

    The aim of this study was to assess acute biochemical changes after the administration of two different pharmaceutical forms of calcium carbonate or milk. The group of 12 young (aged 20-27 years) and 12 older women (aged 63-71 years). After overnight fasting, each of the volunteers received a 1 g of elemental calcium in either form of the tested preparation: powder form of calcium carbonate--Vitacalcin pulvis (Slovakofarma, SR) or effervescent tablet--Calcium 500 mg Pharmavit (Pharmavit, MR) or in 250 ml of milk enriched with the milk calcium complex. Between each test the interval of 1-2 weeks was held. Samples of blood and urine were taken in the fasting state before and during 5.5 h following ingestion of the calcium load. Both calcium carbonate and milk induced a significant increase in the serum ionised calcium (iCa) and a significant decrease in plasma parathormone level (PTH) in comparison with the baseline levels in both groups of women. Comparison between individual preparations and between preparations and milk did not reveal any significant differences in suppression of PTH. Comparison of the effects between young and elderly women did not show any statistically significant difference in any measured parameter. Our results confirmed the good bioavailability of calcium from milk and from both calcium preparations in both age groups of women. Significantly more frequent hypercalcemia in the young women (p effervescent tablet than after the application of calcium in the form of powder or after the application of milk.

  4. Effect of H4R antagonist N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamides and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole on histamine and 4-methylhistamine-induced mast cell response.

    Science.gov (United States)

    Nagarajan, Gomathi; Mariappanadar, Vairamani; Tamizh, Muthu; Kaliappan, Ilango; Elden, Berla Thangam

    2017-06-01

    The histamine plays a decisive role in acute and chronic inflammatory responses and is regulated through its four types of distinct receptors designated from H1 to H4. Recently histamine 4 receptor (H4R) antagonists have been reported to possess various pharmacological effects against various allergic diseases. To investigate the inhibitory effect of N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamide (Compound A) and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole (Compound L) on H4R-mediated calcium mobilization, cytokine IL-13 production, ERK1/2, Akt and NF-κB activation in human mastocytoma cells-1 (HMC-1). Compounds A and L were synthesized chemically and their inhibitory effect on intracellular calcium release was analyzed by Fluo-4 calcium assay, cytokine measurement through ELISA and activation of signaling molecules by western blot. Pre-treatment with compounds A and L significantly reduced the H4R-mediated intracellular calcium release. Histamine and 4-methylhistamine (4-MH) induced Th2 cytokine IL-13 production in HMC-1 cells, was inhibited by compound A (77.61%, 74.25% at 1 μM concentration) and compound L (79.63%, 81.70% at 1 μM concentration). Furthermore, histamine induced the phosphorylation of ERK1/2, Akt and NF-κB was suppressed by compounds A and L at varying levels, ERK1/2 (88%, 86%), Akt (88%, 89%) and NF-κB (89%, 87%) in HMC-1 cells. Taken together these data demonstrate that compound A and compound L may block H4R-mediated downstream signaling events.

  5. Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors.

    Science.gov (United States)

    Darling, Rebecca A; Zhao, Huan; Kinch, Dallas; Li, Ai-Jun; Simasko, Steven M; Ritter, Sue

    2014-07-01

    β-mercaptoacetate (MA) is a drug known to block mitochondrial oxidation of medium- and long-chain fatty acids (FAs) and to stimulate feeding. Because MA-induced feeding is vagally dependent, it has been assumed that the feeding response is mediated by MA's antimetabolic action at a peripheral, vagally innervated site. However, MA's site of action has not yet been identified. Therefore, we used fluorescent calcium measurements in isolated neurons from rat nodose ganglia to determine whether MA has direct effects on vagal sensory neurons. We found that MA alone did not alter cytosolic calcium concentrations in nodose neurons. However, MA (60 μM to 6 mM) significantly decreased calcium responses to both linoleic acid (LA; 10 μM) and caprylic acid (C8; 10 μM) in all neurons responsive to LA and C8. GW9508 (40 μM), an agonist of the FA receptor, G protein-coupled receptor 40 (GPR40), also increased calcium levels almost exclusively in FA-responsive neurons. MA significantly inhibited this response to GW9508. MA did not inhibit calcium responses to serotonin, high K(+), or capsaicin, which do not utilize GPRs, or to CCK, which acts on a different GPR. GPR40 was detected in nodose ganglia by RT-PCR. Results suggest that FAs directly activate vagal sensory neurons via GPR40 and that MA antagonizes this effect. Thus, we propose that MA's nonmetabolic actions on GPR40 membrane receptors, expressed by multiple peripheral tissues in addition to the vagus nerve, may contribute to or mediate MA-induced stimulation of feeding. Copyright © 2014 the American Physiological Society.

  6. Effect of a plant growth regulator prohexadione-calcium on insect pests of apple and pear.

    Science.gov (United States)

    Paulson, G S; Hull, L A; Biddinger, D J

    2005-04-01

    The effect of prohexadione-calcium, a plant growth regulator that inhibits gibberellin metabolism, on Cacopsylla pyricoloa (Foerster) in pear trees, and Choristoneura rosaceana (Harris) and Aphis spireacola Patch, in apple trees was studied. C. pyricoloa and A. spireacola populations were significantly reduced in prohexadione-calcium-treated pear and apple, respectively. Insecticide control of both pests with imidacloprid was synergized in treatments with prohexadione-calcium. In apples treated with prohexadione-calcium, there was a significant reduction in the number of C. rosaceana shelters per tree and amount of fruit injury at harvest attributable to the C. rosaceana. There was an additive effect when tebufenozide was used to control C. rosaceana in trees treated with prohexadione-calcium. Prohexadione-calcium significantly reduced vegetative growth in both pears and apples. Synergistic and additive treatment effects of prohexadione-calcium and pesticides used in this study may be due to better penetration and coverage of pesticides due to reduced foliar growth or to changes in the nutritional quality of the host plants.

  7. 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.

  8. 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

  9. The Effect of Calcium Phosphate‑containing Desensitizing Agent on ...

    African Journals Online (AJOL)

    2016-01-31

    Jan 31, 2016 ... tubules and decrease the permeability of dentin.[6-11]. Calcium-containing desensitizing pastes should ... and favorable reduction in dentin permeability in the oral environment.[14,15] Teethmate Desensitizer .... their margins, were isolated with two layers of nail varnish. The apexes of the teeth were sealed ...

  10. The Effect Of Glycemic Control On Serum Lipids And Calcium ...

    African Journals Online (AJOL)

    control levels in type 2 diabetic patients on the serum lipids and lipoprotein profiles and the serum levels of calcium, phosphate and some other electrolytes. The study was conducted on 81 patients with type 2 diabetes mellitus, who were attending the Outpatient Diabetic and Endocrine Clinic in. King Khaled Hospital, Hail, ...

  11. Effects of gastrin on calcium homeostasis in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Persson, P.; Gagnemo-Persson, R.; Orberg, J.; Chen, D.; Hakanson, R. (University of Lund (Sweden))

    1991-09-01

    As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid-producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. The authors suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa.

  12. The effect of calcium on auxin depletion-induced tomato ...

    African Journals Online (AJOL)

    Yomi

    2012-10-09

    Oct 9, 2012 ... L-1 CaCl2) were applied to each set of dishes to estimate the function of calcium and the IAA transport inhibitor on abscission. One dish without any treatment served as the control. Fifty explants were inserted from the distal end into a Petri dish and ten of such dishes of explants were used as replicates.

  13. Effect of benzimidazole fungicides and calcium chloride on ...

    African Journals Online (AJOL)

    ... fungicides benomyl, methyl-thiophanate, thiabendazole and calcium chloride on fungal decay of pears caused by Alternaria alternata and Penicillium expansum. Both in vitro and in vivo, the efficacy of fungicides alone against the two fungi was shown to be weak and without any practical interest. In vitro, CaCl2 alone was ...

  14. 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

  15. Effect of Agonist and Antagonist on the In Vitro Contractility of Inflamed Vermiform Appendix

    Science.gov (United States)

    Singh, Phani Bhushan; Tiwary, Pushpakant; Singh, Sanjeev K; Pandey, Ratna; Roy, Atanu; Kar, Amrita Ghosh; Basu, Somprakas

    2017-01-01

    Introduction Appendicitis poses a great health problem worldwide. Previous studies demonstrated structural damage to neuronal network and interstitial cell of Cajal in appendicitis. Above observations suggest for the alterations in appendicular motility/contractility in appendicitis. But the mechanisms involved in mediating the contractility in inflamed vermiform appendix is not known till date. Aim The present in vitro study was performed to find out the mechanisms responsible for contractility in the inflamed human vermiform appendix. Materials and Methods Contractions of the longitudinal muscle strips of inflamed appendix were recorded in vitro at 37±0.5°C. Control contractions were recorded for 30 min after an initial tension of 0.5 gram. Initially dose-response experiments of agonists (acetylcholine, serotonin and histamine) were performed separately and the dose that produced maximum contraction was determined with each agonist. This maximal dose of agonist was used to elicit contractions in next series of experiments before and after pre-treatment with appropriate antagonists like atropine, ondansetron (5-HT3 antagonist) and chlorpheniramine maleate respectively. Results Acetylcholine (ACh) and serotonin (5-HT) elicited maximum amplitude of contraction at 10 µM and 1 µM concentration respectively. These contractions were significantly blocked by prior exposure of muscle strips with atropine (100 µM) and ondansetron (10 µM). Histamine produced very low amplitude of contractions in comparison to ACh or 5-HT and did not exhibit dose-response relations. The histamine induced contractions were blocked by H1 antagonist chlorpheniramine maleate (100 µM). Conclusion The observations suggested that the contractility of longitudinal muscle strips of inflamed vermiform appendix in human beings was predominantly mediated by muscarinic and serotonergic (5-HT3) mechanisms, whereas, histaminergic mechanisms played a minor role in mediating the contractility. PMID

  16. Effect of ghrelin receptor antagonist on meal patterns in cholecystokinin type 1 receptor null mice.

    Science.gov (United States)

    Lee, Jennifer; Martin, Elizabeth; Paulino, Gabriel; de Lartigue, Guillaume; Raybould, Helen E

    2011-05-03

    Vagal afferent neurons (VAN) express the cholecystokinin (CCK) type 1 receptor (CCK₁R) and, as predicted by the role of CCK in inducing satiation, CCK₁R⁻/⁻ mice ingest larger and longer meals. However, after a short fast, CCK₁R⁻/⁻ mice ingesting high fat (HF) diets initiate feeding earlier than wild-type mice. We hypothesized that the increased drive to eat in CCK₁R⁻/⁻ mice eating HF diet is mediated by ghrelin, a gut peptide that stimulates food intake. The decrease in time to first meal, and the increase in meal size and duration in CCK₁R⁻/⁻ compared to wild-type mice ingesting high fat (HF) diet were reversed by administration of GHSR1a antagonist D-(Lys3)-GHRP-6 (p<0.05). Administration of the GHSR1a antagonist significantly increased expression of the neuropeptide cocaine and amphetamine-regulated transcript (CART) in VAN of HF-fed CCK₁R⁻/⁻ but not wild-type mice. Administration of the GHSR1a antagonist decreased neuronal activity measured by immunoreactivity for fos protein in the nucleus of the solitary tract (NTS) and the arcuate nucleus of both HF-fed wild-type and CCK₁R⁻/⁻ mice. The data show that hyperphagia in CCK₁R⁻/⁻ mice ingesting HF diet is reversed by blockade of the ghrelin receptor, suggesting that in the absence of the CCK₁R, there is an increased ghrelin-dependent drive to feed. The site of action of ghrelin receptors is unclear, but may involve an increase in expression of CART peptide in VAN in HF-fed CCK₁R⁻/⁻ mice. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Effects of oxytocin-antagonist injections on luteal regression in the goat.

    OpenAIRE

    Homeida, A. M.; Khalafalla, A. E.

    1987-01-01

    Intra-arterial administration of 0.25 ml physiological saline to the non-pregnant goat between days 12 and 20 of the oestrous cycle did not affect luteal regression, which was characterized by decreasing peripheral plasma progesterone concentration, beginning on day 13 of the oestrous cycle, and an increase in the plasma concentration of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) as oestrus approached on about day 20. Intra-arterial administration of oxytocin antagonist (OA) in sali...

  18. Synergistic effects of hypoglycaemic sulphonylureas and antibiotic ionophores upon calcium translocation.

    Science.gov (United States)

    Couturier, E.; Malaisse, W. J.

    1980-01-01

    1 Hypoglycaemic sulphonylureas, such as tolbutamide and gliclazide, provoke the translocation of calcium from an aqueous medium into or across a hydrophobic region. The combined effect of sulphonylureas and antibiotic ionophores upon such a process was investigated. 2 The magnitude of the sulphonylurea-induced translocation of calcium was more marked in the presence than in the absence of A23187. Gliclazide and tolbutamide also enhanced, although less markedly, X537A-mediated calcium translocation. The effect of the sulphonylureas was even less marked in the presence of both ionophores, which acted synergistically in causing calcium translocation. 3 A non-hypoglycaemic sulphonylurea and diazoxide failed to affect ionophore-mediated calcium translocation. Gliclazide failed to enhance X537A-mediated sodium translocation. 4 It is proposed that the primary site of action of hypoglycaemic sulphonylureas upon calcium-dependent physiological processes may correspond to a drug-induced facilitation of calcium transport across the plasma membrane, as mediated by native ionophores. PMID:6781574

  19. [Effect of different culture conditions on carbonic anhydrase from Bacillus mucilaginosus inducing calcium carbonate crystal formation].

    Science.gov (United States)

    Zhou, Xueying; Du, Ye; Lian, Bin

    2010-07-01

    Effect of various culture conditions on the morphology, amount and carbonic anhydrase (CA) activity of Bacillus mucilaginosus were examined, as well as the effect on calcium carbonate crystal forming, shape and amount. The strain was inoculated in N-free or N-containing medium, and the bacterial morphology, number and CA activity were compared under different culture conditions. By collecting different cultures and adding them to the system of calcium carbonate crystallization we studied the relationship between the bacteria and the formation of calcium carbonate crystals. A small number of cell, capsular hypertrophy, lower CA activity in bacterial culture were obtained under N-free culture condition. In contrast, more biomass quantity, thin capsule, and high CA activity were got in the nitrogen-containing culture. In the calcium carbonate crystal system, adding N-free culture of bacteria produced a smooth surface of calcium carbonate crystals, larger volume but small density, the addition N-containing culture of bacteria formed rough surface, bigger density but smaller volume of calcium carbonate crystals. Different culture conditions can cause significant differences in bacterial amounts, capsular thickness and CA activity, and then influence the crystal growth and form of calcium carbonate.

  20. 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.

  1. Effect of a new selective H1 receptor antagonist (levocabastine) in a nasal and conjunctival provocation test.

    Science.gov (United States)

    Pécoud, A; Zuber, P; Kolly, M

    1987-01-01

    Levocabastine is a new selective H1 receptor antagonist. The effect of the drug administered locally was compared to placebo in a quantified nasal and conjunctival provocation test with allergens performed in patients allergic to grass pollen. In the nasal provocation test, levocabastine was able to increase the 'reaction threshold' (dose of allergen necessary to trigger allergic symptoms) in 9 out of 12 patients; the drug inhibited rhinorrhea and sneezing, but not nasal obstruction. In the conjunctival provocation test, the 'reaction threshold' clearly increased in 10 out of 11 patients. The local administration of levocabastine might be useful in allergic rhinitis and conjunctivitis.

  2. 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 ...

  3. 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.

  4. Skeletal effects of a gastrin receptor antagonist in H+/K+ATPase beta subunit KO mice.

    Science.gov (United States)

    Aasarød, Kristin M; Ramezanzadehkoldeh, Masoud; Shabestari, Maziar; Mosti, Mats P; Stunes, Astrid K; Reseland, Janne E; Beisvag, Vidar; Eriksen, Erik Fink; Sandvik, Arne K; Erben, Reinhold G; Schüler, Christiane; Boyce, Malcolm; Skallerud, Bjørn H; Syversen, Unni; Fossmark, Reidar

    2016-08-01

    Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin. In this study, we wanted to examine whether inhibition of the gastrin/CCK2 receptor influences bone quality in these mice. KO and WT mice were given either the gastrin/CCK2 receptor antagonist netazepide dissolved in polyethylene glycol (PEG) or only PEG for 1year. We found significantly lower bone mineral content and BMD, as well as inferior bone microarchitecture in KO mice compared with WT. Biomechanical properties by three-point bending test also proved inferior in KO mice. KO mice receiving netazepide exhibited significantly higher cortical thickness, cortical area fraction, trabecular thickness and trabecular BMD by micro-CT compared with the control group. Three-point bending test also showed higher Young's modulus of elasticity in the netazepide KO group compared with control mice. In conclusion, we observed that the gastrin receptor antagonist netazepide slightly improved bone quality in this mouse model, suggesting that hypergastrinemia may contribute to deteriorated bone quality during acid inhibition. © 2016 Society for Endocrinology.

  5. 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.

  6. Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney.

    Science.gov (United States)

    Sutton, R A; Wong, N L; Dirks, J H

    1979-05-01

    Clearance and micropuncture studies have been performed in dogs to examine the effects of acute and chronic metabolic acidosis and acute alkalosis on tubular sodium and calcium transport. Acute metabolic acidosis, induced by the infusion of hydrochloric acid, decreased proximal fluid reabsorption and increased the fractional delivery of sodium and calcium to the distal tubule, but not to the final urine. In comparison with normal dogs, dogs with chronic metabolic acidosis (induced by feeding ammonium chloride) showed an increase in proximal fluid reabsorption and a dissociation of calcium from sodium reabsorption more distally, leading to an increased delivery of calcium relative to sodium at the distal tubule and in the final urine. The infusion of sodium bicarbonate to correct chronic metabolic acidosis, both in intact and thyroparathyroidectomized (TPTX) dogs, reduced proximal fluid reabsorption and caused a selective enhancement of calcium reabsorption relative to sodium in the more distal nephron, resulting in a reversal of the dissociation observed in acidosis, both at the distal tubule and in the final urine. By contrastin fusion of sodium chloride in parathyroid-intact acidotic dogs did not reduce proximal fluid reabsorption or enhance tubular calcium reabsorption. In nonacidotic dogs, both intact and TPTX, infusion of sodium bicarconate to induce acute alkalosis resulted in selhese data demonstrate the presence of a component of tubular calcium reabsorption situated beyond the proximal tubule, which is inhibited by chronic (but not acute) metabolic acidosis and enhanced by metabolic alkalosis (or bicarbonate infusion) independently of parathyroid hormone.

  7. Effects of Calcium Superphosphate Additive on Nitrogen Conservation During Dead-pig Composting

    Directory of Open Access Journals (Sweden)

    LEI Ping

    2017-05-01

    Full Text Available To study the effects of calcium superphosphate additive on nitrogen conservation, an experiment of 30 days dead-pig composting was carried out. Three mixtures were treated with different amount of calcium superphosphate additive of 0%(CK, 5%(T1 and 10%(T2. The results showed that each composte temperature higher than 50 ℃ remained above 10 days, meeting the requirements of hygiene index about the compost rotten. The pH of composting with calcium superphosphate was significantly decreased, while NH4+-N, NH3-N, total nitrogen contents were significant higher than the control. 5% and 10% calcium superphosphate addition increased the total nitrogen contents by 10.7%, 10.1%, respectively. The seed germination index(GI of 5% calcium superphosphate addition was up to 101.4% on the 14th day, which was significant higher than the contrast. It demonstrated that calcium superphosphate could accelerate maturity during dead-pig compositng. Thus, calcium superphosphate as an additive in dead-pig composting could decrease nitrogen losses, which would bring prospects of application in dead-pig composting.

  8. 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.

  9. 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.

  10. Effects of brefeldin A on pollen germination and tube growth. Antagonistic effects on endocytosis and secretion.

    Science.gov (United States)

    Wang, Qinli; Kong, Lingan; Hao, Huaiqing; Wang, Xiaohua; Lin, Jinxing; Samaj, Jozef; Baluska, Frantisek

    2005-12-01

    We assessed the effects of brefeldin A (BFA) on pollen tube development in Picea meyeri using fluorescent marker FM4-64 as a membrane-inserted endocytic/recycling marker, together with ultrastructural studies and Fourier transform infrared analysis of cell walls. BFA inhibited pollen germination and pollen tube growth, causing morphological changes in a dose-dependent manner, and pollen tube tip growth recovered after transferring into BFA-free medium. FM4-64 labeling showed typical bright apical staining in normally growing P. meyeri pollen tubes; this apical staining pattern differed from the V-formation pattern found in angiosperm pollen tubes. Confocal microscopy revealed that exocytosis was greatly inhibited in the presence of BFA. In contrast, the overall uptake of FM4-64 dye was about 2-fold that in the control after BFA (5 microg mL(-1)) treatment, revealing that BFA stimulated endocytosis in a manner opposite to the induced changes in exocytosis. Transmission electron microscopic observation showed that the number of secretory vesicles at the apical zone dramatically decreased, together with the disappearance of paramural bodies, while the number of vacuoles and other larger organelles increased. An acid phosphatase assay confirmed that the addition of BFA significantly inhibited secretory pathways. Importantly, Fourier transform infrared microspectroscopy documented significant changes in the cell wall composition of pollen tubes growing in the presence of BFA. These results suggest that enhanced endocytosis, together with inhibited secretion, is responsible for the retarded growth of pollen tubes induced by BFA.

  11. Growth hormone secretagogues exert differential effects on skeletal muscle calcium homeostasis in male rats depending on the peptidyl/nonpeptidyl structure.

    Science.gov (United States)

    Liantonio, Antonella; Gramegna, Gianluca; Carbonara, Giuseppe; Sblendorio, Valeriana Teresa; Pierno, Sabata; Fraysse, Bodvaël; Giannuzzi, Viviana; Rizzi, Laura; Torsello, Antonio; Camerino, Diana Conte

    2013-10-01

    The orexigenic and anabolic effects induced by ghrelin and the synthetic GH secretagogues (GHSs) are thought to positively contribute to therapeutic approaches and the adjunct treatment of a number of diseases associated with muscle wasting such as cachexia and sarcopenia. However, many questions about the potential utility and safety of GHSs in both therapy and skeletal muscle function remain unanswered. By using fura-2 cytofluorimetric technique, we determined the acute effects of ghrelin, as well as of peptidyl and nonpeptidyl synthetic GHSs on calcium homeostasis, a critical biomarker of muscle function, in isolated tendon-to-tendon male rat skeletal muscle fibers. The synthetic nonpeptidyl GHSs, but not peptidyl ghrelin and hexarelin, were able to significantly increase resting cytosolic calcium [Ca²⁺]i. The nonpeptidyl GHS-induced [Ca²⁺]i increase was independent of GHS-receptor 1a but was antagonized by both thapsigargin/caffeine and cyclosporine A, indicating the involvement of the sarcoplasmic reticulum and mitochondria. Evaluation of the effects of a pseudopeptidyl GHS and a nonpeptidyl antagonist of the GHS-receptor 1a together with a drug-modeling study suggest the conclusion that the lipophilic nonpeptidyl structure of the tested compounds is the key chemical feature crucial for the GHS-induced calcium alterations in the skeletal muscle. Thus, synthetic GHSs can have different effects on skeletal muscle fibers depending on their molecular structures. The calcium homeostasis dysregulation specifically induced by the nonpeptidyl GHSs used in this study could potentially counteract the beneficial effects associated with these drugs in the treatment of muscle wasting of cachexia- or other age-related disorders.

  12. The effects of polyamine agonists and antagonists on N-methyl-D-aspartate-induced depolarizations of amphibian motoneurons in situ.

    Science.gov (United States)

    Hackman, John C; Holohean, Alice M

    2010-04-14

    Polyamines have been found to reduce proton inhibition of isolated N-methyl-D-aspartate (NMDA) channels recorded in vitro. This study examines the role of polyamine modulation of motoneuronal excitation in situ, with an emphasis on possible interactions with NMDA-mediated depolarization of motoneurons and receptor mediated modulation of NMDA receptors by L-glutamate and serotonin (5-HT). Motoneuron membrane potential changes were electrotonically recorded in situ from the ventral root of isolated, hemisected amphibian spinal cords using sucrose gap techniques. The methods provided highly stable recordings (polyamine antagonist arcaine or the allosteric modulator ifenprodil had no effect on NMDA-induced changes in motoneuron membrane potentials recorded in situ but blocked the effects of spermine. Synthalin did not block spermine enhancement of NMDA-induced depolarization of motoneurons but mimicked Mg(2+) block of the NMDA channel. The data provide evidence that the proton block of the NMDA receptor is maximized in frog motoneurons in situ and also for a spermine specific polyamine site on native NMDA receptors of motoneurons that can enhance NMDA-induced depolarization when activated. Polyamines do not appear to be constitutively active at the motoneurons recorded since polyamine antagonists had no effect on either membrane depolarization or modulation of NMDA receptors. Published by Elsevier B.V.

  13. Biochemical and ultrastructural studies suggest that the effects of thapsigargin on human platelets are mediated by changes in intracellular calcium but not by intracellular histamine

    DEFF Research Database (Denmark)

    Saxena, S P; McNicol, A; Becker, A B

    1992-01-01

    was observed at 1 microM Tg. Preincubation of platelets with inhibitors of histamine metabolizing enzymes had little effect on intracellular histamine levels in platelets stimulated by 0.5 microM Tg. In addition, the inhibitors of histidine decarboxylase (HDC), alpha-methyl histidine (alpha-MH) and alpha......-fluoromethyl histidine (alpha-FMH) failed to inhibit Tg-induced aggregation. The intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl (DPPE), inhibited Tg-induced aggregation but with IC50 values dependent on the concentration of agonist used. The inhibitory effects...... of DPPE on Tg-induced aggregation were not reversed by the addition of histamine to saponin-permeabilized platelets suggesting non-histamine mediated effects of DPPE on Tg-induced aggregation. Tg stimulated an increase in the cytosolic free calcium concentration which was unaffected by DPPE indicating...

  14. Calcium hydroxide as low cost adsorbent for the effective removal of indigo carmine dye in water

    Directory of Open Access Journals (Sweden)

    Thimmasandra Narayan Ramesh

    2017-02-01

    Full Text Available Adsorption of indigo carmine dye onto calcium hydroxide was investigated in this work. The variation in the pH, adsorbent dose, dye concentration, duration and the temperature was evaluated. Adsorption of indigo carmine dye onto calcium hydroxide was effective at pH 12 (50 min and follows Langmuir-type isotherm behaviour. The adsorption process follows pseudo-second order rate kinetics. Enthalpy, entropy, free energy and the activation energy parameters have been reported.

  15. Calcium hydroxide as low cost adsorbent for the effective removal of indigo carmine dye in water

    OpenAIRE

    Thimmasandra Narayan Ramesh; Devarahosahally Veeranna Kirana; Ashwathaiah Ashwini; T.R. Manasa

    2017-01-01

    Adsorption of indigo carmine dye onto calcium hydroxide was investigated in this work. The variation in the pH, adsorbent dose, dye concentration, duration and the temperature was evaluated. Adsorption of indigo carmine dye onto calcium hydroxide was effective at pH 12 (50 min) and follows Langmuir-type isotherm behaviour. The adsorption process follows pseudo-second order rate kinetics. Enthalpy, entropy, free energy and the activation energy parameters have been reported.

  16. The effects of PRX-07034, a novel 5-HT6 antagonist, on cognitive flexibility and working memory in rats

    Science.gov (United States)

    Mohler, Eric G.; Baker, Phillip M.; Gannon, Kimberly S.; Jones, Simon S.; Shacham, Sharon; Sweeney, John A.

    2012-01-01

    Rationale Accumulating evidence indicates that schizophrenia and autism spectrum disorder patients are marked by cognitive deficits in working memory and strategy switching. There is accumulating evidence that 5-hydroxytryptamine (5-HT)6 receptors may serve as a useful target to improve cognitive functioning. Objectives In the present experiments, the novel 5-HT6 antagonist, PRX-07034, was examined for its selectivity of the 5-HT6 receptor, as well as its effect on delayed spontaneous alternation and strategy switching. Methods The binding affinity of PRX-07034 to the 5-HT6 receptor, other 5-HT receptors, as well as other G-protein coupled receptors, ion channels, and transporters was evaluated. Cyclic AMP production was measured from transfected HEK-293 cells. In separate behavioral experiments, rats received different doses of PRX-07034 (0.1, 1, or 3 mg/kg, i.p.) 30 min prior to delayed spontaneous alternation testing or prior to the acquisition and switch phases in a place–response switch test. Results The results indicated that PRX-07034 is both a potent (Ki = 4–8 nM) and highly selective 5-HT6 receptor antagonist (≥100-fold selectivity for the 5-HT6 receptor compared to 68 other GPCRs, ion channels, and transporters, except D3 (Ki = 71 nM) and 5-HT1B (Ki = 260 nM) receptors. For cyclic AMP quantification, PRX-07034 demonstrated antagonist activity (IC50 = 19 nM) without an effect on basal levels and did not show any agonist activity up to 10 µM. PRX-07034 at 1 and 3 mg/kg (but not 0.1 mg/kg) significantly enhanced delayed spontaneous alternation. The drug at 1 and 3 mg/kg also enhanced switching between a place and response strategy, but did not affect initial learning of either a place or response discrimination. Conclusions These findings demonstrate that PRX-07034 is a selective 5-HT6 receptor antagonist that may represent a novel treatment for enhancing working memory and cognitive flexibility. PMID:21989804

  17. 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.

  18. Effect of cationic and anionic surfactants on the application of calcium carbonate nanoparticles in paper coating.

    Science.gov (United States)

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

    2014-02-26

    Modification of calcium carbonate particles with surfactant significantly improves the properties of the calcium carbonate coating on paper. In this study, unmodified and CTAB (hexadecyltetramethylammonium bromide)- 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 using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, zeta potential measurements, thermal gravimetric analysis (TGA), and transmission electron microscopy (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 commercial ground (GCC) calcium carbonate-coated papers. The results show that the obtained calcium carbonate nanoparticles are in the calcite phase. The morphology of the prepared calcium carbonate nanoparticles is rhombohedral, and the average particle diameter is less than 100 nm. Compared to commercial GCC, the use of unmodified and CTAB- and oleate-modified calcium carbonate nanoparticles in paper coating improves the properties of paper. The highest measured paper properties were observed for paper coated with oleate-modifed nanoparticles, where an increase in smoothness (decrease in paper roughness) (+23%), brightness (+1.3%), whiteness (+2.8%), and opacity (+2.3%) and a decrease in air permeability (-26%) was obtained with 25% less coat weight. The water contact angle at a drop age time of 10 min was about 112° for the paper

  19. Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice

    DEFF Research Database (Denmark)

    Joseph, Lauren; Thomsen, Morgane

    2017-01-01

    Muscarinic M1/M4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (SD) effects, but the receptor subtypes mediating those...... effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M1, M2, or M4 receptors (M1-/-, M2-/-, M4-/-), as well as control wild-type mice and outbred Swiss-Webster mice...... with cocaine. In intact animals, antagonists with high affinity at M1/M4 receptors partially substituted for cocaine and increased the SD effect of cocaine, while M2-preferring antagonists did not substitute, and reduced the SD effect of cocaine. The cocaine-like effects of scopolamine were absent in M1...

  20. 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.

  1. Pharmacological characterisation of a structurally novel α2C-adrenoceptor antagonist ORM-10921 and its effects in neuropsychiatric models.

    Science.gov (United States)

    Sallinen, Jukka; Holappa, Johanna; Koivisto, Ari; Kuokkanen, Katja; Chapman, Hugh; Lehtimäki, Jyrki; Piepponen, Petteri; Mijatovic, Jelena; Tanila, Heikki; Virtanen, Raimo; Sirviö, Jouni; Haapalinna, Antti

    2013-10-01

    The α2-adrenoceptors (ARs) are important modulators of a wide array of physiological responses. As only a few selective compounds for the three α2-AR subtypes (α2A , α2B and α2C ) have been available, the pharmacological profile of a new α2C-selective AR antagonist ORM-10921 is reported. Standard in vitro receptor assays and antagonism of α2, and α1-AR agonist-evoked responses in vivo were used to demonstrate the α2C-AR selectivity for ORM-10921 which was tested in established behavioural models related to schizophrenia and cognitive dysfunction with an emphasis on pharmacologically induced hypoglutamatergic state by phencyclidine or MK-801. The Kb values of in vitro α2C-AR antagonism for ORM-10921 varied between 0.078-1.2 nM depending on the applied method. The selectivity ratios compared to α2A-AR subtype and other relevant receptors were 10-100 times in vitro. The in vivo experiments supported its potent α2C-antagonism combined with only a weak α2A-antagonism. In the pharmacodynamic microdialysis study, ORM-10921 was found to increase extracellular dopamine levels in prefrontal cortex in the baseline conditions. In the behavioural tests, ORM-10921 displayed potent antidepressant and antipsychotic-like effects in the forced swimming test and prepulse-inhibition models analogously with the previously reported results with structurally different α2C-selective AR antagonist JP-1302. Our new results also indicate that ORM-10921 alleviated the NMDA-antagonist-induced impairments in social behaviour and watermaze navigation. This study extends and further validates the concept that α2C -AR is a potential therapeutic target in CNS disorders such as schizophrenia or Alzheimer's disease and suggests the potential of α2C-antagonism to treat such disorders. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  2. 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.

  3. 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

  4. Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats.

    Science.gov (United States)

    Chauhan, G; Ray, K; Sahu, S; Roy, K; Jain, V; Wadhwa, M; Panjwani, U; Kishore, K; Singh, S B

    2016-11-19

    Sleep deprivation (SD) upsurges intracellular levels of adenosine, impairs adult neuronal cell proliferation (NCP) and cognition while caffeine, a non-selective adenosine A1 receptor (A1R) antagonist improves cognition and adult NCP during SD. We examined the selective antagonistic effects of adenosine A1R using 8-cyclopentyl-1,3-dimethylxanthine (8-CPT) on impairment of spatial reference memory and adult NCP during 48h SD. Adult male Sprague Dawley rats were sleep deprived for 48h, using an automatic cage vibrating stimulus based on animal activity. Spatial reference memory was tested as a measure of cognitive performance employing Morris Water Maze. Rats were given 8-CPT dissolved in 50% dimethyl sulfoxide (DMSO), twice daily (10mg/kg, i.p.) along with 5-bromo-2-deoxyuridine (BrdU) (50mg/kg/day, i.p.). The rats treated with 8-CPT showed significantly short mean latency and path-length to reach the platform compared to the SD rats. Consistent with these findings, 8-CPT-treated group was found to have significantly increased the number of BrdU, Ki-67 and doublecortin (DCX) positive cells. However, no significant difference was seen in NeuN expression in the Dentate Gyrus (DG). Brain-derived neurotropic factor (BDNF) expression in the DG and CA1 region was observed to decrease significantly after SD and be rescued by 8-CPT treatment. Furthermore, latency to reach platform showed a negative correlation with number of BrdU, DCX type-1 cells and BDNF expression in DG. Thus, it may be concluded that treatment with 8-CPT, an adenosine A1R antagonist during SD mitigates SD induced decline in spatial reference memory and adult NCP possibly via up regulation of BDNF levels in DG and CA1 regions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. 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.

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

    Science.gov (United States)

    Newton, Claire L; 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.

  7. Effect of platelet-activating factor antagonist WEB 2086 on microcirculatory disorders in acute experimental pancreatitis of graded severity.

    Science.gov (United States)

    Mann, Oliver; Tiefenbacher, Wolf-Jonas; Kaifi, Jussuf; Schneider, Claus; Kluth, Dirk; Bloechle, Christian; Yekebas, Emre; Izbicki, Jakob R; Strate, Tim

    2009-01-01

    Platelet-activating factor (PAF) is an important mediator of inflammation and postulated to be involved in the pathogenesis of acute pancreatitis. In this study, we evaluated the therapeutic effect of PAF antagonist WEB 2086 in acute experimental pancreatitis of graded severity in rats. According to a block design, 64 animals were randomly allocated to 8 groups. Severe necrotizing pancreatitis was induced by intraductal infusion of taurocholic acid (4%, 0.4 mL), and the combination of glycodeoxycholic acid (10 mmol/L, 1.0 mL/kg, intraductal infusion) and cerulein (5 microg/kg per hour, intravenous) was applied to induce intermediate pancreatitis, or cerulein alone (5 microg/kg per hour, intravenous) to establish edematous pancreatitis. WEB 2086 was given 15 minutes after beginning the induction of pancreatitis. Pancreatic microcirculation was analyzed in vivo with an epiluminescent microscope. Histopathology was evaluated by a validated score. Trypsinogen-activating peptide and serum amylase were analyzed sequentially. WEB 2086 had no significant influence on the breakdown of microcirculation, leukocyte adherence, histopathological damage, and amylase levels in severe necrotizing pancreatitis, intermediate pancreatitis, and edematous pancreatitis. Only in intermediate pancreatitis was there a significant reduction of trypsinogen-activating peptide levels. In our study, PAF antagonist WEB 2086 had no beneficial effect on microcirculation in acute experimental pancreatitis.

  8. The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.

    Science.gov (United States)

    Nakamura, Yoshihisa; Hamajima, Yuki; Suzuki, Motohiko; Esaki, Shinichi; Yokota, Makoto; Oshika, Masanori; Takagi, Ippei; Yasui, Keiko; Miyamoto, Naoya; Sugiyama, Kazuko; Nakayama, Meiho; Murakami, Shingo

    2016-08-01

    Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Effects of energy controllable steep pulses on intracellular calcium concentration and cell membrane potential.

    Science.gov (United States)

    Dong, X-J; Luo, X-D; Xiong, L; Mi, Y; Hu, L-N

    2014-01-01

    Our previous experiments showed that steep pulses could kill tumor cells, but the mechanism is unclear yet. This study was to probe the effects of different dosages of energy controllable steep pulses on intracellular concentration of dissociative calcium ion ([Ca2+]i) and cell membrane potential. The mammary carcinoma cells MDA-MB-231 were divided into control group and 5 different dosages of Energy Controllable Steep Pulses (ECSP) treatment groups. The calcium ion in each group was labeled by Fluo-3/AM individually and the cell membrane potential was labeled by DiBAC4 (3). The mean fluorescence intensity of fluorescent probe in mammary carcinoma cells was observed in quiet state by laser confocal microscopy after ECSP treatment The changes of calcium concentration and cell membrane potential in cells after ECSP treatment were analyzed. The changes of intracellular [Ca2+]i after ECSP treatment were also observed with and without calcium ion outside of the cells. The calcium ion outside of cells influx with lower dosage of pulse in quiet state. With the dosage increase, the intracellular calcium ion outflow. In real time kinetic detection, the mean fluorescence intensity of intracellular calcium ion was increased with the pulse electric field intensity raised in the lower ECSP. When the voltage was 285V, frequency was 100Hz, the [Ca2+]i decreased. The increase of intracellular calcium ion concentration was decreased without calcium ion than with calcium ion outside of cells, but still raised gradually. The lower dosage of ECSP could induce the fluorescence intensity of DiBAC4 (3) in cells increase, which showed that the lower dosage of ECSP could induce the depolarization of cells. With the dosage raised, the fluorescence intensity of DiBAC4 (3) in cells attenuated. This dosage of ECSP could induce the superpolarization of cell membrane. The lower dosage of ECSP can induce the depolarization of cell membrane and induce the inter flow of calcium ion outside of cell

  10. The effect of calcium withdrawal on the structure and function of the toad bladder.

    Science.gov (United States)

    Hays, R M; Singer, B; Malamed, S

    1965-06-01

    Previous reports have indicated that calcium is necessary to support active sodium transport by the toad bladder, and may be required as well in the action of vasopressin on both toad bladder and frog skin. The structure and function of the toad bladder has been studied in the absence of calcium, and a reinterpretation of the previous findings now appears possible. When calcium is withdrawn from the bathing medium, epithelial cells detach from one another and eventually from their supporting tissue. The short-circuit current (the conventional means of determining active sodium transport) falls to zero, and vasopressin fails to exert its usual effect on short-circuit current and water permeability. However, employing an indirect method for the estimation of sodium transport (oxygen consumption), it is possible to show that vasopressin exerts its usual effect on Q(oo2) when sodium is present in the bathing medium. Hence, it appears that the epithelial cells maintain active sodium transport when calcium is rigorously excluded from the bathing medium, and continue to respond to vasopressin. The failure of conventional techniques to show this can be attributed to the structural alterations in the epithelial layer in the absence of calcium. These findings may provide a model for the physiologic action of calcium in epithelia such as the renal tubule.

  11. Effects of DFA IV in rats: calcium absorption and metabolism of DFA IV by intestinal microorganisms.

    Science.gov (United States)

    Saito, K; Hira, T; Suzuki, T; Hara, H; Yokota, A; Tomita, F

    1999-04-01

    Di-D-fructose-2,6':6,2'-dianhydride (DFA IV) is a disaccharide consisting of two fructose residues that can be prepared from levan by levan fructotransferase from Arthrobacter nicotinovorans GS-9, and it can be expected to have novel physiological functions from its unique structure. In this study, the effects of DFA IV on calcium absorption and the metabolism of DFA IV by intestinal microorganisms were studied in rats to examine the physiological functions of DFA IV. The apparent calcium absorption in rats fed with DFA IV was significantly higher than that in the control rats, and it seems that calcium absorption had almost been completed at the end of the small intestine. DFA IV also increased the calcium absorption in in vitro experiments, using everted jejunal and ileal sacs, and this result supports the finding obtained in the in vivo experiments. These results indicate that DFA IV may have a function for increasing the calcium absorption in the small intestine of rats. However, the effect in the large intestine could not be clearly observed because of the lack of calcium that reached there. The results of analyses of organic acids in the cecal and colonic contents and of DFA IV in the fecal, cecal, and colonic contents showed that the metabolism of DFA IV by microorganisms in the large intestine progressed gradually, and that DFA IV was converted mainly to acetate, butyrate, and lactate.

  12. 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.

  13. 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.

  14. Effect of cadence on volume and myoelectric activity during agonist-antagonist paired sets (supersets) in the lower body.

    Science.gov (United States)

    Antunes, Lara; Bezerra, Ewertton de S; Sakugawa, Raphael L; Dal Pupo, Juliano

    2018-01-26

    The aim of this study was to investigate the effect of cadence on volume load (VLoad) and muscle activity during agonist-antagonist paired sets (APS) in the lower body. Twelve trained men (24.0 ± 3.3 years; 78.3 ± 9.7 kg; 1.77 ± 0.58 m) volunteered to participate in this study. After the 10 maximum repetition test for leg extension and seated leg curl, participants performed three experimental protocols: first protocol (traditional)-three sets of only leg extension (60 bpm); second protocol (fast cadence)-three sets of leg extension, with each set preceded by one set on the seated leg curl with fast cadence (90 bpm); third protocol (slow cadence)-similar to the second, but seated leg curl with slow cadence (40 bpm). The total number of repetitions, VLoad and the electromyography activity for the vastus lateralis, vastus medialis and rectus femoris muscles were recorded. The VLoad was higher during APS than the traditional method, but the cadence (fast or slow) of antagonist exercise did not influence VLoad. Muscle activity of vastus lateralis was higher during traditional protocol; on the other hand, rectus femoris showed higher activity on APS fast cadence protocol, indicating that APS has a different influence on quadriceps components.

  15. The Antagonistic Effect of Mycotoxins Deoxynivalenol and Zearalenone on Metabolic Profiling in Serum and Liver of Mice

    Directory of Open Access Journals (Sweden)

    Jian Ji

    2017-01-01

    Full Text Available Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON and zearalenone (ZEN, through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious “antagonistic effect” in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB/globulin (GLO, reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an “antagonistic effect” on liver metabolism of mice.

  16. [Effect of mu- and kappa-opioid receptor antagonists on aggressiveness of male mice with repeated experience of aggression].

    Science.gov (United States)

    Bondar', N P

    2012-06-01

    Mu and kappa opioid receptors often show opposite actions in the regulation ofphysiological functions and behaviors including aggressive behavior. In the present study, effects ofmu antagonist CTAP (1 and 2 mg/kg, sc) and kappa antagonist nor-BNI (0.5 mg/kg, sc) on the manifestation of aggressive behavior of C57BL/6J male mice with a short (3 days) and a long (20 days) experience of victories in daily intermale confrontations were investigated. It was shown that the mice with a short experience of aggression are tolerant to blockade of both mu and kappa opioid receptors. In the mice with a long experience of aggression, CTAP increased latency of aggression in dose-dependent manner, but did not change the duration of attacks. Nor-BNI had no influence on the behavior of the male mice with a long experience of aggression in the intermale confrontation. The possible changes in opioid receptor sensitivity in C57BL/6J male mice under the influence ofa long experience of aggression are discussed.

  17. Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis

    Directory of Open Access Journals (Sweden)

    Ji-Yao Li

    2011-06-01

    Full Text Available Hypertension is a risk factor for osteoporosis. Animal and epidemiological studies demonstrate that high blood pressure is associated with increased calcium loss, elevated parathyroid hormone, and increased calcium movement from bone. However, the mechanism responsible for hypertension-related osteoporosis remains elusive. Recent epidemiological studies indicate the benefits of Angiotensin II Receptors Blockade (ARB on decreasing fracture risks. Since receptors for angiotensin II, the targets of ARB, are expressed in both osteoblasts and osteoclasts, we postulated that angiotensin II plays an important role in hypertension-related osteoporosis. Cbfa1 and RANKL, the important factors for maintaining bone homeostasis and key mediators in controlling osteoblast and osteoclast differentiation, are both regulated by cAMP-dependent signaling. Angiotensin II along with factors such as LDL, HDL, NO and homocysteine that are commonly altered both in hypertension and osteoporosis, can down-regulate the expression of Cbfa1 but up-regulate RANKL expression via the cAMP signaling pathway. We thus hypothesized that, by altering the ratio of Cbfa1/RANKL expression via the cAMP-dependent pathway, angiotensin II differently regulates osteoblast and osteoclast differentiation leading to enhanced bone resorption and reduced bone formation. Since ARB can antagonize the adverse effect of angiotensin II on bone by lowering cAMP levels and modifying other downstream targets, including LDL, HDL, NO and Cbfa1/RANKL, we propose the hypothesis that the antagonistic effects of ARB may also be exerted via cAMP signaling pathway.

  18. The effects of dopamine receptor 1 and 2 agonists and antagonists on sexual and aggressive behaviors in male green anoles.

    Directory of Open Access Journals (Sweden)

    Alexandra N Smith

    Full Text Available The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa. In reptiles there have been few studies examining the relationship between dopaminergic receptors and social behaviors. We therefore examined the effects of D1 and D2 agonists and antagonists on sexual and aggressive behaviors in the male green anole lizard (Anolis carolinensis. Treatment with high doses of both D1 and D2 agonists was found to impair both sexual and aggressive behaviors. However, the D1 agonist treatment was also found to impair motor function, suggesting that those effects were likely nonspecific. Lower doses of both agonists and antagonists failed to affect social behaviors. These findings provide some evidence for D2 receptor regulation of social behaviors, but in contrast with previous research, these effects are all inhibitory and no effects were found for manipulations of D1 receptors. A potential reason for the lack of more widespread effects on social behaviors using moderate or low drug doses is that systemic injection of drugs resulted in effects throughout the whole brain, thus affecting counteracting circuits which negated one another, making measurable changes in behavioral output difficult to detect. Future studies should administer drugs directly into brain regions known to regulate sexual and aggressive behaviors.

  19. The effects of dopamine receptor 1 and 2 agonists and antagonists on sexual and aggressive behaviors in male green anoles.

    Science.gov (United States)

    Smith, Alexandra N; Kabelik, David

    2017-01-01

    The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa. In reptiles there have been few studies examining the relationship between dopaminergic receptors and social behaviors. We therefore examined the effects of D1 and D2 agonists and antagonists on sexual and aggressive behaviors in the male green anole lizard (Anolis carolinensis). Treatment with high doses of both D1 and D2 agonists was found to impair both sexual and aggressive behaviors. However, the D1 agonist treatment was also found to impair motor function, suggesting that those effects were likely nonspecific. Lower doses of both agonists and antagonists failed to affect social behaviors. These findings provide some evidence for D2 receptor regulation of social behaviors, but in contrast with previous research, these effects are all inhibitory and no effects were found for manipulations of D1 receptors. A potential reason for the lack of more widespread effects on social behaviors using moderate or low drug doses is that systemic injection of drugs resulted in effects throughout the whole brain, thus affecting counteracting circuits which negated one another, making measurable changes in behavioral output difficult to detect. Future studies should administer drugs directly into brain regions known to regulate sexual and aggressive behaviors.

  20. Assessment of membrane protection by /sup 31/P-NMR effects of lidocaine on calcium-paradox in myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hirosumi; Yoshiyama, Minoru; Teragaki, Masakazu; Takeuchi, Kazuhide; Takeda, Takeda; Ikata, Mari; Ishikawa, Makoto; Miura, Iwao

    1989-01-01

    In studying calcium paradox, perfused rat hearts were used to investigate the myocardial protective effects of lidocaine. Intracellular contents of phosphates were measured using the /sup 31/P-NMR method. In hearts reexposed to calcium, following 3 minute calcium-free perfusion, a rapid contracture occurred, followed by rapid and complete disappearance of intracellular phosphates with no resumption of cardiac function. In hearts where lidocaine was administered from the onset of the calcium-free perfusion until 2 minutes following the onset of reexposure to calcium, both intracellular phosphates and cardiac contractility were maintained. Therefore, it can be said that cell membranes were protected by lidocaine.

  1. Study on the Effect of Calcium and Potassium Spray on Date Bunch Fading Disorder

    Directory of Open Access Journals (Sweden)

    Hosein Shekofteh

    2017-02-01

    Full Text Available Introduction: Date bunch fading disorder has been one of the most important problems, which caused economic damage to date plantation area of Iran. It has been first reported on Mozafti cultivar in Kahnuj area, Kerman province. It has often been observed on soft and mid ripening cultivars such as Mozafti, Mordaseng and Kalote. Furthermore, it usually appears on Mozafti cultivar when fruits change from Khalal to Rutab stage. The most important symptoms of this disorder are sudden wilting of fruits and necrotic strips on the upper surface of the main bunch stalk. Incidence and development of these symptoms increase by high temperature, low relative humidity, and hot and dry wind. Several research studies have been carried out on this disorder so far, but the only research about the effect of nutrition on disorder was performed by Rosta (2003. The aim of the present study was to investigate the effect of calcium and potassium spray on date bunch fading and some traits of date fruit in Rigan region, Kerman province. Materials and Methods: The experiment was conducted based on randomized complete block designs with three replicates in Rigan located in east south of Kerman province, Iran, in 2012. Treatments were: T1: control, T2: spray of calcium nitrate at the concentration of 5 ppm, T3: spray of potassium sulfate at the concentration of 5 ppm, and T4: combined spray of calcium nitrate and potassium sulfate at the concentration of 5 ppm. Treatments were applied at Kimri, Hobabok and Khalal stages. Sampling was performed from 3 date palms (3 bunches from each date palm were selected randomly at the second date harvest. Totally, the traits of 200 fruits were measured in each date palm. The traits measured in the present study were: fruit length, fruit diameter, fruit weight, stone weight, stone diameter, and bunch fading percentage. Results and Discussions: According to the data of variance analysis, treatments had a significant effect on wet fruit

  2. Effect of articaine on calcium transport in sarcoplasmic reticulum membranes isolated from medial pterygoid muscle.

    Science.gov (United States)

    Sánchez, Gabriel A; Di Croce, Daniel E; Richard, Susana B; Takara, Delia

    2012-01-01

    Local anesthetics used in dentistry have myotoxic effects. Articaine, also known as carticaine, is one of the local anesthetics most widely used in clinical dentistry. The aim of this work was to describe its effect on the sarcoplasmic reticulum Ca-ATPase isolated from medial pterygoid muscle. Ca-ATPase enzymatic activity was determined by a colorimetric method and ATP-dependent calcium uptake with a radioisotopic technique. Articaine inhibited both Ca-ATPase activity and calcium uptake in a concentration-dependent manner. Both inhibitory effects became evident at articaine concentrations lower than those employed in clinical dentistry. Half-maximal inhibitory concentrations (K) were 15.1 +/- 1.8 mM (n = 6) and 25.2 +/- 1.6 mM (n = 6) for enzymatic activity and calcium uptake, respectively. Preincubation of sarcoplasmic reticulum membranes with articaine enhanced Ca-ATPase activity in the absence of calcium ionophore, suggesting an ionophoric-like effect of the local anesthetic. We conclude that the inhibitory effect of articaine on the sarcoplasmic reticulum Ca-ATPase isolated from medial pterygoid muscle is due to a direct interaction of the anesthetic with the enzyme and to the increased membrane permeability to calcium induced by this drug.

  3. The effect of pigeon yolk sac fluid on the growth behavior of calcium carbonate crystals.

    Science.gov (United States)

    Song, Juan; Cheng, Haixia; Shen, Xinyu; Tong, Hua

    2015-03-01

    Previous experiments have proved that thermodynamically unstable calcium carbonate vaterite can exist for long periods in the yolk sac of a pigeon embryo. The aim of this article was to demonstrate the effect of in vitro mineralization of yolk sac fluid on calcium carbonate by direct precipitation. Experiments were conducted using pigeon yolk sac fluid and using lecithin extracted from pigeon yolk sac fluid as a control to investigate the regulating effects of the organic components in the embryo on the formation of the calcium carbonate precipitate. Multiple characterization methods were employed to study the various morphological patterns, sizes, crystal growth, and crystal phase transformations of the calcium carbonate precipitates as regulated by the yolk sac fluid extracted at different stages of incubation. The experimental results demonstrate that as the incubation proceeds towards the later stages, the composition and environmental features of the yolk sac fluid become more favorable for the formation of relatively unstable calcium carbonate phases with high energies of the vaterite state. The experiments conducted with extracted lecithin as the template for crystal growth yielded similar results. A large amount of organic molecules with polar functional groups carried by the yolk sac fluid have strong effects and can both initially induce the crystallization and regulate the aggregation of calcium carbonate. Furthermore, this regulation process is found to be closely related to the lecithin contained in yolk sac fluid. These observations confirm the changes in yolk sac fluid composition during incubation have significant effects on the production of vaterite, which implicates the calcium transport during embryo growth. © 2015 Poultry Science Association Inc.

  4. The Effects of a Dairy Probiotic Product, Espar, on Salivary Calcium and Mutans Streptococci

    Directory of Open Access Journals (Sweden)

    Hamidreza Poureslami

    2013-08-01

    Full Text Available Background and aims. Espar is a dairy product of probiotic nature that contains useful bacteria and high calcium content. The aim of this study was to analyze effects of daily consumption of Espar on the number of salivary mutans streptococci and the level of calcium content in a population of 15 to 17 year-old female students. Materials and methods. A double-blind randomized crossover study (n = 50 of healthy female adolescents was implemented in four stage intervals. The first and third stages were ‘run-in’ and ‘wash-out’ intervals. For the second and fourth stages, two weeks long in duration, the participants consumed 100 grams of Espar or 200 grams of plain yogurt. At the end of each stage, the number of salivary mutans streptococci and the level of calcium content were documented. Results. There was a statistically significant decrease in the number of salivary mutans streptococci subsequent to Espar consumption when compared to ordinary yogurt (p < 0.01. Additionally, salivary calcium content increased significantly subsequent to the consumption of Espar and yogurt. However, Espar yielded a higher level of significant increase in salivary calcium when compared to plain yogurt (p < 0.01. Conclusion. This study found that daily consumption of Espar increased the salivary calcium level while decreasing mutans streptococci of the saliva.

  5. 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.

  6. 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

  7. Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes.

    Science.gov (United States)

    Makitani, Kouki; Nakagawa, Shota; Izumi, Yasuhiko; Akaike, Akinori; Kume, Toshiaki

    2017-05-01

    Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+). Twenty four hours pretreatment of donepezil reduced the bradykinin-induced [Ca(2+)]i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes

    Directory of Open Access Journals (Sweden)

    Kouki Makitani

    2017-05-01

    Full Text Available Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca2+]i in cultured astrocytes. Bradykinin-induced [Ca2+]i increase was inhibited by the exposure to thapsigargin, which depletes Ca2+ stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca2+. Twenty four hours pretreatment of donepezil reduced the bradykinin-induced [Ca2+]i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes.

  9. Effect of calcium carbonate on hardening, physicochemical properties, and in vitro degradation of injectable calcium phosphate cements.

    NARCIS (Netherlands)

    Sariibrahimoglu, K.; Leeuwenburgh, S.C.G.; Wolke, J.G.C.; Yubao, L.; Jansen, J.A.

    2012-01-01

    The main disadvantage of apatitic calcium phosphate cements (CPCs) is their slow degradation rate, which limits complete bone regeneration. Carbonate (CO(3)(2)(-)) is the common constituent of bone and it can be used to improve the degradability of the apatitic calcium phosphate ceramics. This study

  10. Effects of thyroid hormones on calcium contents and 45Ca exchange in rat skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Everts, M.E.; Clausen, T.

    1986-09-01

    In 4-wk-old rats, pretreatment with L-triiodothyronine (T3) increased calcium content by 100% and the 30-min /sup 45/Ca uptake by 64% in the soleus, whereas the extensor digitorum longus (EDL) muscle showed no significant change. The stimulation of /sup 45/Ca uptake was resistant to dantrolene and methoxyverapamil (D600) and could not be attributed to altered permeability of the plasma membrane to calcium, but appears to reflect increased net accumulation of calcium in intracellular pools. The stimulating effect of high K0 (20 mM) on /sup 45/Ca uptake was more pronounced in soleus than in EDL and could be suppressed by dantrolene and D600. The results indicate that the effects of T3 on calcium content and /sup 45/Ca exchange are primarily exerted on muscles containing a large proportion of slow-twitch, oxidative fibers. In soleus muscle from hyperthyroid rats the stimulating effects of high K0 on /sup 45/Ca uptake and lactate production were, respectively, 3.4 and 4.5 times larger than in those obtained from controls. These observations further support the earlier proposed idea (C. van Hardeveld and T. Clausen. Am. J. Physiol. 247 (Endocrinol. Metab. 10): E421-E430, 1984) that the metabolic effects of thyroid hormone depend on the availability of cellular as well as extracellular calcium.

  11. Effects of functional groups and soluble matrices in fish otolith on calcium carbonate mineralization.

    Science.gov (United States)

    Ren, Dongni; Li, Zhuo; Gao, Yonghua; Feng, Qingling

    2010-10-01

    Calcium carbonate mineralization is significantly influenced by organic matrices in vivo. The effect mainly relies on functional groups in proteins. In order to study the influence of functional groups on calcium carbonate mineralization, -OH, -NH2 and -COOH groups were grafted onto single crystal silicon chips, and such modified chips were used as substrates in in vitro mineralization experiments. An x-ray photoelectron spectroscopy (XPS) test was conducted to examine the grafting efficiency, and the three groups were successfully grafted. Calcium carbonate mineralization on a modified silicon substrate was examined by a scanning electron microscope (SEM) and x-ray diffraction (XRD), and the results showed that the effects of -OH, -NH2 and -COOH groups were quite different. Furthermore, a water-soluble protein matrix (WSM) and an acid-soluble protein matrix (ASM) extracted from fish otolith were adsorbed onto the -COOH-modified silicon substrate, and the effects of the protein matrices on calcium carbonate mineralization were studied. The results showed that both WSM and ASM of lapillus could mediate aragonite crystallization, but the size and morphology of the formed crystals were different. The WSM and ASM of asteriscus adsorbed on the silicon substrate had little effect on calcium carbonate mineralization; almost all the crystals were calcite, while both asteriscus WSM and ASM in solution could mediate vaterite crystals, and the morphologies of vaterite crystal aggregates were different.

  12. Studies on calcium phosphate precipitation: effects of metal ions used in dental materials.

    Science.gov (United States)

    Okamoto, Y; Hidaka, S

    1994-12-01

    The effects of 26 metal ions, of which 23 are used in dental materials, on the conversion of amorphous calcium phosphate (ACP) to hydroxyapatite (HAP) in vitro were studied. From the effects on both the rate of HAP transformation and induction time, effects of metal ions were classified into three types; inhibitory (in the order: nickel, tin, cobalt, manganese, copper, zinc, gallium, thallium, molybdenum, cadmium, antimony, magnesium, and mercury); ineffective (cesium, titanium, chromium, iron [ferrous], iridium, palladium, platinum, silver, gold, aluminum, and lead); and stimulatory (iron [ferric] and indium). These results suggest that metal ions used in dental materials may modify the precipitation of oral calcium phosphate.

  13. Aryl Hydrocarbon Receptor Antagonists Mitigate the Effects of Dioxin on Critical Cellular Functions in Differentiating Human Osteoblast-Like Cells

    Directory of Open Access Journals (Sweden)

    Chawon Yun

    2018-01-01

    Full Text Available The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation. Since there are dozens of AhR ligands present in cigarette smoke, we utilized dioxin as a prototype ligand to activate the receptor and explore its effects on pro-osteogenic biomarkers and other factors critical to osteogenesis using a human osteoblast-like cell line. We also explored the capacity for AhR antagonists to protect against dioxin action in this context. We found dioxin to inhibit osteogenic differentiation, whereas co-treatment with various AhR antagonists protected against dioxin action. Dioxin also negatively impacted cell adhesion with a corresponding reduction in the expression of integrin and cadherin proteins, which are known to be involved in this process. Similarly, the dioxin-mediated inhibition of cell migration correlated with reduced expression of the chemokine receptor CXCR4 and its ligand, CXCL12, and co-treatment with antagonists restored migratory capacity. Our results suggest that AhR activation may play a role in the bone regenerative response in humans exposed to AhR activators, such as those present in cigarette smoke. Given the similarity of our results using a human cell line to previous work done in murine cells, animal models may yield data relevant to the human setting. In addition, the AhR may represent a potential therapeutic target for orthopedic patients who smoke cigarettes, or those who are exposed to secondhand smoke or other

  14. In vitro effects of both dopaminergic and enkephalinergic antagonists on the ovarian growth of Cherax quadricarinatus (Decapoda, Parastacidae), at different periods of the reproductive cycle.

    Science.gov (United States)

    Cahansky, Alejandra Valeria; Medesani, Daniel Alberto; Chaulet, Anouk; Rodríguez, Enrique Marcelo

    2011-01-01

    The in vitro effect of both spiperone (dopaminergic antagonist) and naloxone (enkephalinergic antagonist), was assayed on small pieces of ovary dissected from C. quadricarinatus females, with the eventual addition of some neuroendocrine organs, such as thoracic ganglion or eyestalk tissue. The incorporation of tritiated leucine by the ovary was measured in order to estimate the ovarian growth. During the post-reproductive period, both mentioned antagonists were able to significantly stimulate the ovary in the presence of thoracic ganglion, but did not produce any significant effect in the preparation containing ovary and eyestalk tissue, or only ovary. No significant effects of the assayed antagonists were noted during the pre-reproductive period. These results were in accordance with previous models describing the neuroendocrine control of crustacean reproduction, and represent new findings about the hormonal context in different periods of the reproductive cycle of crayfish. Besides, by means of the experimental combination of the tested antagonists with dopamine or met-enkephalin, a new model dealing with the interaction of these two neurotransmitters on the hormonal secretion of thoracic ganglion has been proposed. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. 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

  16. Effect of yeast antagonist in combination with heat treatment on postharvest blue mold decay and Rhizopus decay of peaches.

    Science.gov (United States)

    Zhang, Hongyin; Wang, Lei; Zheng, Xiaodong; Dong, Ying

    2007-04-01

    The potential of using heat treatment alone or in combination with an antagonistic yeast for the control of blue mold decay and Rhizopus decay of peaches caused by Penicillium expansum and Rhizopus stolonifer respectively, and in reducing natural decay development of peach fruits, as well as its effects on postharvest quality of fruit was investigated. In vitro tests, spore germination of pathogens in PDB was greatly controlled by the heat treatment of 37 degrees C for 2 d. In vivo test to control blue mold decay of peaches, heat treatment and antagonist yeast, as stand-alone treatments, were capable of reducing the percentage of infected wounds from 92.5% to 52.5% and 62.5%, respectively, when peach fruits stored at 25 degrees C for 6 d. However, in fruit treated with combination of heat treatment and Cryptococcus laurentii, the percentage of infected wounds of blue mold decay was only 22.5%. The test of using heat treatment alone or in combination with C. laurentii to control Rhizopus decay of peaches gave a similar result. The application of heat treatment and C. laurentii resulted in low average natural decay incidences on peaches after storage at 4 degrees C for 30 days and 20 degrees C for 7 days ranging from 40% to 30%, compared with 20% in the control fruit. The combination of heat treatment and C. laurentii was the most effective treatment, and the percentage of decayed fruits was 20%. Heat treatment in combination with C. laurentii had no significant effect on firmness, TSS, ascorbic acid or titratable acidity compared to control fruit. Thus, the combination of heat treatment and C. laurentii could be an alternative to chemicals for the control of postharvest decay on peach fruits.

  17. Effect of soy protein/animal protein ratio on calcium metabolism of the rat.

    Science.gov (United States)

    Yoon, Gun Ae; Hwang, Hye Jin

    2006-04-01

    This study examined the effects of a ratio of soy protein to animal protein on bone metabolism of rats. Experimental groups were a high soy protein group (200 g of soy protein and 0 g of casein per kilogram of diet; HSoy), a middle soy protein group (100 g of soy protein and 100 g of casein per kilogram of diet; MSoy), a low soy protein group (50 g of soy protein and 150 g of casein per kilogram of diet; LSoy), and a no soy protein group (0 g of soy protein and 200 g of casein per kilogram of diet; NSoy). Calcium excretion and retention, biochemical parametrically related calcium metabolism, and bone mineral density were measured. Statistical analysis was performed with SAS software. Urinary excretion of calcium was significantly high in the LSoy and NSoy groups, and there was no difference in absorption of calcium across experimental groups. Calcium retention was significantly higher in the HSoy and MSoy groups than in the LSoy and NSoy groups. Experimental groups showed no differences in the activity of alkaline phosphatase. The casein group (NSoy) showed a remarkably lower degree of serum osteocalcin concentration. The concentration of deoxypyridinoline in urine showed an increasing tendency, i.e., HSoy and MSoy protein/soy proteins, its concentration increases. Wet weight of the femur appeared to be significantly greater in the MSoy and LSoy groups than in the NSoy group. Ash content of the femur and bone density were highest in the MSoy group, with the ratio of 1:1 between soy protein and animal protein. This study indicated that deoxypyridinoline concentration was lower and the density of osteocalcin was higher in the MSoy group than in the NSoy group, and that calcium retention was high and bone mineral density was the highest in the MSoy group. The ratio of soy to animal protein that seemed to have the most positively significant effect on calcium metabolism was 1:1.

  18. Interleukin Expression after Injury and the Effects of Interleukin-1 Receptor Antagonist

    Science.gov (United States)

    Chamberlain, Connie S.; Leiferman, Ellen M.; Frisch, Kayt E.; Brickson, Stacey L.; Murphy, William L.; Baer, Geoffrey S.; Vanderby, Ray

    2013-01-01

    Ligament healing follows a series of complex coordinated events involving various cell types, cytokines, as well as other factors, producing a mechanically inferior tissue more scar-like than native tissue. Macrophages provide an ongoing source of cytokines to modulate inflammatory cell adhesion and migration as well as fibroblast proliferation. Studying interleukins inherent to ligament healing during peak macrophage activation and angiogenesis may elucidate inflammatory mediators involved in subsequent scar formation. Herein, we used a rat healing model assayed after surgical transection of their medial collateral ligaments (MCLs). On days 3 and 7 post-injury, ligaments were collected and used for microarray analysis. Of the 12 significantly modified interleukins, components of the interleukin-1 family were significantly up-regulated. We therefore examined the influence of interleukin-1 receptor antagonist (IL-1Ra) on MCL healing. Transected rat MCLs received PBS or IL-1Ra at the time of surgery. Inhibition of IL-1 activation decreased pro-inflammatory cytokines (IL-1α, IL-1β, IL-12, IL-2, and IFN-γ), myofibroblasts, and proliferating cells, as well as increased anti-inflammatory cytokines (IL-10), endothelial cells/blood vessel lumen, M2 macrophages, and granulation tissue size without compromising the mechanical properties. These results support the concept that IL-1Ra modulates MCL-localized granulation tissue components and cytokine production to create a transient environment that is less inflammatory. Overall, IL-1Ra may have therapeutic potential early in the healing cascade by stimulating the M2 macrophages and altering the granulation tissue components. However, the single dose of IL-1Ra used in this study was insufficient to maintain the more regenerative early response. Due to the transient influence on most of the healing components tested, IL-1Ra may have greater therapeutic potential with sustained delivery. PMID:23936523

  19. Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl₄-Induced Skeletal Muscle Injury.

    Science.gov (United States)

    Hwang, Ok-Kyung; Park, Jin-Kyu; Lee, Eun-Joo; Lee, Eun-Mi; Kim, Ah-Young; Jeong, Kyu-Shik

    2016-02-08

    TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl₄ intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl₄-treatment group (n = 7), and CCl₄ + losartan treatment group (n = 7). After CCl₄ treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl₄ + losartan group (p losartan group (p losartan group compared to the corresponding levels in the control group (p losartan promotes muscle repair from injury via blockade of TGF-β1 signaling.

  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 hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

  1. The effectiveness of post-culture liquids of antagonistic bacteria in the protection of soybean from soil-borne fungi

    Directory of Open Access Journals (Sweden)

    Elżbieta Patkowska

    2012-12-01

    Full Text Available The objective of the paper was to determine the effectiveness of post-culture liquids of Bacillus sp. Bsch 19 and Pseudomonas sp. Psch 16 in the protection of soybean from soil-borne fungi. The use of post-culture liquids of those bacteria in seed dressing positively affected the number, healthiness and yielding of soybean plants. The plants were mainly infected by Fusarium spp., Phoma exigua var. exigua, Rhizoctonia solani and Sclerotinia sclerotiorum. Those fungi were isolated much more rarely from the plants in combinations with the use of post-culture liquids of antagonistic bacteria as compared with the plants from the control combination, i.e. without seed dressing. A reverse relation was found for the occurrence of saprophytic fungi from the genera of Gliocladium, Penicillium and Trichoderma

  2. In vitro effects of salicylic acid, calcium and copper ions on growth ...

    African Journals Online (AJOL)

    The in vitro effects of single and combined application of calcium ion (Ca2+), copper ion (Cu2+) and salicylic acid (SA) were evaluated on growth and sporulation of Ganoderma boninense. In poison medium test, T7-(Ca+Cu+SA) showed effective control of G. boninense in-vitro with EC50 and EC90 values of ...

  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. Effect of oral administration of AZD8309, a CXCR2 antagonist, on the severity of experimental pancreatitis.

    Science.gov (United States)

    Malla, Sudarshan R; Kärrman Mårdh, Carina; Günther, Annett; Mahajan, Ujjwal M; Sendler, Matthias; D'Haese, Jan; Weiss, Frank Ulrich; Lerch, Markus M; Hansen, Mark Berner; Mayerle, Julia

    2016-01-01

    Acute pancreatitis is a common gastrointestinal disorder burdened with a high mortality. Two pathophysiological events during experimental pancreatitis are thought to determine the clinical course: premature digestive protease activation and tissue infiltration by inflammatory cells. We have investigated the effect of AZD8309, a potent and orally bioavailable antagonist of the chemokine receptor CXCR2, which has been proposed to regulate the transmigration of neutrophils. Male C57BL6 mice (25-30 g) received gavage feeding of AZD8309 (50 mg/kg/BW) or mannitol (controls) twice daily starting 3 h prior to pancreatitis induction. Mild pancreatitis was induced by i.p. caerulein administration (50 μg/kg BW), severe pancreatitis by intraductal taurocholate (2%). Pancreas, lung, and serum was harvested up to 48 h after pancreatitis induction and used for histopathology, amylase, lipase, cathepsin B, trypsin, and elastase activity measurements, myeloperoxidase (MPO) content and cytokine concentrations. Oral administration of AZD8309 significantly reduced MPO in the pancreas and lungs (8 h & 24 h) and reduced intrapancreatic trypsin and elastase activity (8 h) in caerulein-pancreatitis. In taurocholate-pancreatitis AZD8309 reduced cathepsin B activity and MPO. Serum cytokine levels were reduced by AZD8309 as well as histopathological damage. The CXCR2 antagonist AZD8309 reduced the transmigration of neutrophils as well as intrapancreatic protease activation in experimental pancreatitis. This effect was sufficient to reduce the overall severity of the disease. CXCR2 may therefore be a viable therapeutic target and AZD8309 a suitable agent for the treatment of acute pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  5. The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial.

    Science.gov (United States)

    The, Gerard K H; Bleijenberg, Gijs; Buitelaar, Jan K; van der Meer, Jos W M

    2010-05-01

    Accumulating data support the involvement of the serotonin (5-hydroxytryptamine [5-HT]) system in the pathophysiology of chronic fatigue syndrome. Neuropharmacologic studies point to a hyperactive 5-HT system, and open-label treatment studies with 5-HT(3) receptor antagonists have shown promising results. In this randomized controlled clinical trial, the effect of ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome. A randomized, placebo-controlled, double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial. Participants received either ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables were fatigue severity (Checklist Individual Strength fatigue severity subscale [CIS-fatigue]) and functional impairment (Sickness Impact Profile-8 [SIP-8]). The effect of ondansetron was assessed by analysis of covariance. Data were analyzed on an intention-to-treat basis. All patients were recruited between June 2003 and March 2006. Thirty-three patients were allocated to the ondansetron condition, 34 to the placebo condition. The 2 groups were well matched in terms of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment. This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome. www.trialregister.nl: ISRCTN02536681. ©Copyright 2010 Physicians Postgraduate Press, Inc.

  6. Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1.

    Science.gov (United States)

    Zhang, Xiaoqian

    2013-01-01

    The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1.

  7. The effect of antagonistic micro-organisms on the brood of honeybees (Apis mellifera) and bumblebees (Bombus terrestris) 2003

    NARCIS (Netherlands)

    Steen, van der J.J.M.; Dik, A.J.

    2002-01-01

    Several plant pathogenic fungi enter the plant trough open flowers. Spores of antagonistic micro-organisms present on the flowers can successfully compete with the possible pathogens. Honeybees and bumblebees can be used for transporting these antagonistic micro-organisms from the hive into flowers

  8. Relaxant effect of tetrazepam on rat uterine smooth muscle: role of calcium movement.

    Science.gov (United States)

    Perez-Guerrero, C; Herrera, M D; Marhuenda, E

    1996-11-01

    Tetrazepam is a benzodiazepine derivative clinically used as a muscle relaxant. The aim of the present work was to examine its effect on uterine smooth muscle of the rat in estrus. Tetrazepam required micromolar concentrations to relax contractile responses induced by KCl and acetylcholine in Ca2+ solution, but not oxytocin-induced contraction. In Ca(2+)-free solution, tetrazepam inhibited Ca(2+)-induced contractions in depolarized uterus and vanadate-induced contractions. We suggest that tetrazepam relaxes contractile responses induced by activation of voltage-sensitive calcium channels and receptor-operated calcium channels with little selectivity or that it antagonizes the effect of calcium at subsequent steps, possibly intracellular stores sensitive to vanadate but not sensitive to oxytocin. The inhibition of contraction of rat uterus is not related to high-affinity peripheral benzodiazepine binding sites.

  9. The effects of hyaluronic acid, calcium hydroxide, and dentin adhesive on rat odontoblasts and fibroblasts.

    Science.gov (United States)

    Bogović, Ana; Nižetić, Jana; Galić, Nada; Zelježić, Davor; Micek, Vedran; Mladinić, Marin

    2011-06-01

    The aim of this study was to investigate the effects and efficiency of pulp capping preparations based on hyaluronic acid, calcium hydroxide, and dentin adhesive on the pulp tissue of Sprague-Dawley rats. The rats were killed and extracted teeth sectioned transversely through the pulp. The slices were placed in a RPMI 1640 cell culture medium supplemented with 10 % foetal calf serum. During 14 days of cultivation cultures were treated with preparations that contained hyaluronic acid (Gengigel Prof®), and calcium hydroxide (ApexCal®), or with dentin adhesive (Excite®). Cellularity and viability of fibroblasts and odontoblasts was analysed using a haemocytometer. Hyaluronic acid proved most efficient and the least toxic for direct pulp capping. Even though calcium hydroxide and dentin adhesive demonstrated a higher degree of cytotoxicity, their effects were still acceptable in terms of biocompatibility.

  10. The co-effect of collagen and magnesium ions on calcium carbonate biomineralization

    Energy Technology Data Exchange (ETDEWEB)

    Jiao Yunfeng [Department of Materials Science and Engineering, Biomaterials Laboratory, Tsinghua University, Beijing 100084 (China); Feng Qingling [Department of Materials Science and Engineering, Biomaterials Laboratory, Tsinghua University, Beijing 100084 (China)]. E-mail: biomater@mail.tsinghua.edu.cn; Li Xiaoming [Department of Materials Science and Engineering, Biomaterials Laboratory, Tsinghua University, Beijing 100084 (China)

    2006-05-15

    The process of calcium carbonate biomineralization in the solution containing collagen and magnesium ions was studied in this paper. The results were characterized by using powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effect rules were obtained by the cooperation of collagen and magnesium ions in different concentration. The experiment results showed that in the presence of both collagen and magnesium ions, aragonite and vaterite were precipitated at low Mg/Ca ion concentration ratio, while only aragonite with regular spherical morphology was precipitated at high Mg/Ca ion concentration ratio. It indicated that collagen has a promotional effect on magnesium ions in controlling the polymorph of calcium carbonate crystal. A much wider range of calcium carbonate morphologies was observed in the presence of both collagen and magnesium ions. The experiments suggested that collagen acts in combination with magnesium ions to inhibit calcite crystal growth, while favoring the formation of aragonite crystals.

  11. Effect of laser photocoagulation combined with calcium dobesilate for diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Zhen-Tao Zhu

    2017-02-01

    Full Text Available AIM: To investigate the clinical effect of panretinal laser photocoagulation combined with calcium hydroxide in the treatment of diabetic retinopathy(DR. METHODS: Selected 120 cases(204 eyesof DR patients who were treated in our hospital from January 2014 to December 2015 were randomly divided into study group(116 eyes in 66 patientswith calcium hydroxide, control group(88 eyes in 54 patients. Two groups were treated with panretinal laser photocoagulation, and the clinical effect of the two groups were compared. RESULTS: At 6mo after surgery, BCVA of study group was higher than that of control group, the difference was statistically significant(PPPP>0.05. CONCLUSION: Compared with simple laser photocoagulation, panretinal laser photocoagulation combined with calcium hydroxide for III - IV stage DR reduce fluorescein leakage area and CMT.

  12. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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

  15. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    Energy Technology Data Exchange (ETDEWEB)

    Bevilacqua, M.; Vago, T.; Norbiato, G. (Servizio di Endocrinologia, Milano, (Italy))

    1991-02-01

    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 ({sup 3}H)-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 Ca{sup 2}{sup +} and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca{sup 2}{sup +}-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 Ca{sup 2}{sup +} to the medium. This result was consistent with a competition between Ca{sup 2}{sup +} 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 Ca{sup 2}{sup +}.

  16. Calcium induces long-term legacy effects in a subalpine ecosystem.

    Directory of Open Access Journals (Sweden)

    Urs Schaffner

    Full Text Available Human activities have transformed a significant proportion of the world's land surface, with profound effects on ecosystem processes. Soil applications of macronutrients such as nitrate, phosphorus, potassium or calcium are routinely used in the management of croplands, grasslands and forests to improve plant health or increase productivity. However, while the effects of continuous fertilization and liming on terrestrial ecosystems are well documented, remarkably little is known about the legacy effect of historical fertilization and liming events in terrestrial ecosystems and of the mechanisms involved. Here, we show that more than 70 years after the last application of lime on a subalpine grassland, all major soil and plant calcium pools were still significantly larger in limed than in unlimed plots, and that the resulting shift in the soil calcium/aluminium ratio continues to affect ecosystem services such as primary production. The difference in the calcium content of the vegetation and the topmost 10 cm of the soil in limed vs. unlimed plots amounts to approximately 19.5 g m(-2, equivalent to 16.3% of the amount that was added to the plots some 70 years ago. In contrast, plots that were treated with nitrogen-phosphorus-potassium fertilizer in the 1930s did not differ from unfertilized plots in any of the soil and vegetation characteristics measured. Our findings suggest that the long-term legacy effect of historical liming is due to long-term storage of added calcium in stable soil pools, rather than a general increase in nutrient availability. Our results demonstrate that single applications of calcium in its carbonated form can profoundly and persistently alter ecosystem processes and services in mountain ecosystems.

  17. 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.

  18. CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain

    Directory of Open Access Journals (Sweden)

    Liu X

    2017-09-01

    Full Text Available Xiaoming Liu, Hongjun Liu, Lihua Dai, Bingjie Ma, Ke Ma Pain Management Center, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: Chemokine CXCL12 and its receptor CXCR4 have been reported to play a critical role in neurogenesis and neuronal differentiation. Recently, some reports have implicated this chemokine signaling in the pathogenesis of many kinds of pain. However, its role in neuropathic pain (NP is still largely unclear. This study explored the distribution and function of CXCR4 in spinal cord (SC dorsal horn (DH in a rat L5 spinal nerve ligation (SNL model. Methods: Rats received repeated intrathecal injection of CXCR4 antagonist AMD3100. Behavioral assessments were conducted using a traditional “up–down” method. The spinal CXCL12 contents were measured by enzyme linked immunosorbent assay. The expression and distribution of CXCR4 in the SC were determined by immunoflurescence and Western blot. GlyRα3 expressions were also measured by Western blot or immunofluorescence. Results: SNL induced CXCL12–CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (P<0.01. CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (P<0.01 vs the SNL group on Day 14 and Day 21. Conclusion: CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP. Keywords: neuropathic pain, CXCL12, CXCR4, GlyRα3, L5 spinal nerve ligation

  19. 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.

    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

  20. 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....

  1. Concentration dependent effect of calcium on brain mitochondrial bioenergetics and oxidative stress parameters

    Directory of Open Access Journals (Sweden)

    Jignesh D. Pandya

    2013-12-01

    Full Text Available Mitochondrial dysfunction following traumatic brain and spinal cord injury (TBI and SCI plays a pivotal role in the development of secondary pathophysiology and subsequent neuronal cell death. Previously, we demonstrated a loss of mitochondrial bioenergetics in the first 24 h following TBI and SCI initiates a rapid and extensive necrotic event at the primary site of injury. Within the mitochondrial derived mechanisms, the cross talk and imbalance amongst the processes of excitotoxicity, Ca2+ cycling/overload, ATP synthesis, free radical production, and oxidative stress damage ultimately leading to mitochondrial damage followed by neuronal cell death and loss of behaviors. Mitochondria are one of the most important organelles that regulate for intracellular calcium (Ca2+ homeostasis; and are equipped with a tightly regulated Ca2+ transport system. However, owing to the lack of consensus and the link between the downstream effects of calcium in published literature, we undertook a systematic in vitro study for measuring concentration dependent effects of calcium (100-1000 nmols/mg mitochondrial protein on mitochondrial respiration, enzyme activities, reactive oxygen/nitrogen species (ROS/RNS generation, membrane potential (∆Ψ and oxidative damage markers in isolated brain mitochondria. We observed a dose- and time-dependent inhibition of mitochondrial respiration by calcium without influencing mitochondrial pyruvate dehydrogenase complex (PDHC and NADH dehydrogenase (Complex I enzyme activities. We observed dose-dependent decreased production of hydrogen peroxide and total ROS/RNS species generation by calcium and no significant changes in protein and lipid oxidative damage markers. These results may shed new light on the prevailing dogma of the direct effects of calcium on mitochondrial bioenergetics, free radical production and oxidative stress parameters that are primary regulatory mitochondrial mechanisms following neuronal injury.

  2. Effect of calcium hydroxide pastes and vehicles on root canal dentin microhardness

    Directory of Open Access Journals (Sweden)

    María G Pacios

    2014-01-01

    Full Text Available Background: Calcium hydroxide pastes used in the endodontic therapy may produce changes in the physical properties of the dentin. Objective: The purpose of this study was to evaluate the effect of calcium hydroxide pastes and their vehicles on microhardness of root canal dentin. Materials and Methods: Sixty maxillary anterior teeth were used. The crowns of the teeth were removed at the cemento-enamel junction. Canals were instrumented, horizontally sectioned into 2 segments, embedded in acrylic resin, and polished. A total of 120 specimens were randomly divided into 12 groups. Specimens stayed in contact with the vehicles or the pastes prepared with the calcium hydroxide powder and the same vehicles. The vehicles are: Distilled water, chlorhexidine, carticaine in the anesthetic solution, propylene glycol, monochlorophenol and monochlorophenol - propylene glycol. The references Vickers microhardness were obtained prior the application of the medicaments. Samples were then exposed to the medicaments for 3, 7, and 14 days, and microhardness measured again. The results were statistically analyzed by one-way ANOVA, Tukey test, and regression. Results: All vehicles and pastes, except distilled water, significantly decreased the microhardness of the root dentin; however, calcium hydroxide + camphorated monochlorophenol - propylene glycol and camphorated monochlorophenol - propylene glycol showed the highest decrease. Conclusion: Vehicles contribute to calcium hydroxide reduction of root canal dentin microhardness as constituent of endodontic pastes.

  3. 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. © IMechE 2015.

  4. Effects of lactose on calcium absorption and secretion by rat ileum.

    Science.gov (United States)

    Favus, M J; Angeid-Backman, E

    1984-03-01

    The direct effects of lactose on net intestinal calcium absorption were determined by measuring unidirectional steady-state calcium fluxes in vitro under short-circuited conditions in segments of rat ileum. The isosmotic mucosal additions in segments of rat ileum. The isosmotic mucosal addition of lactose (160 mM) increased net calcium absorption (J net) by increasing the absorptive flux from mucosa to serosa (Jm----s) and reducing the secretory flux from serosa to mucosa (Js----m). Lactose also reduced tissue conductance and short-circuit current and reversed tissue polarity. 1,25-Dihydroxyvitamin D3 administration (50 ng/day for 4 days) increased J net from secretion to no net flux (Jm----s = Js----m), and lactose increased J net further to net absorption. Removal of sodium from the medium, like lactose addition, increased J net by increasing Jm----s and reducing Js----m. The replacement of medium sodium with choline abolished a further increase of J net by lactose. These results show that lactose increases net calcium absorption in the absence of transepithelial electrochemical or osmotic gradients. Transcellular calcium transport may be stimulated by lactose by hyperpolarization of the brush border as a result of reduced mucosal sodium.

  5. Effect of Blumea balsamifera extract on the phase and morphology of calcium oxalate crystals.

    Science.gov (United States)

    Montealegre, Charlimagne M; De Leon, Rizalinda L

    2017-10-01

    Calcium oxalate crystals are found in majority of kidney stones with calcium oxalate monohydrate (COM) as one of the primary types of kidney stones. Various methods of treatment exist, including herbal treatment in the Philippines that uses the medicinal herb Blumea balsamifera (B. balsamifera). The effect of B. balsamifera extract on the morphology of calcium oxalate crystals was studied by light microscopy, image analysis, powder X-ray diffraction and scanning electron microscopy. The extract decreased the crystal size by 5.22%-82.62% depending on the degree of supersaturation. Through analysis of the projected area of the crystals, the extract was found to shift the phase of the crystals from COM to calcium oxalate dihydrate (COD). This shift in phase is significant with a COM to COD shift of 88.26% at 0.5 mg/mL of extract and 91.53% at 1.0 mg/mL of extract. Scanning election microscopic (SEM) images revealed aggregation of crystals at 0 mg/mL of extract. At 1.0 mg/mL of extract, the scanning electron micrographs showed discernible crystal unit boundaries. B. balsamifera extract was observed to have decreased crystal size, shifted crystal phase from COM to COD and prevented the aggregation of calcium oxalate crystals.

  6. HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H1 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Agha Zeeshan Mirza

    2017-02-01

    Full Text Available The method has been developed and validated for the simultaneous determination of pioglitazone and H1-receptor antagonists (fexofenadine, cetirizine and levocetirizine in formulations and human serum. Utilizing HPLC techniques, an assay was designed to determine the in vitro effects of pioglitazone on H1-receptor antagonists. Obtained results were verified using the UV spectrophotometric technique. First-derivative values versus concentrations were used to plot calibration curves of these drugs and were found to similar with the HPLC data. The availability of pioglitazone remained unchanged in absence or presence of fexofenadine, cetirizine and levocetirizine. This in vitro analysis confirms the harmless co-administration of pioglitazone and H1-receptor antagonists, and can serve as the foundation for designing further in vivo studies.

  7. Effects of arotinolol, an alpha- and beta-adrenoceptor antagonist, on renin release from rat kidney cortical slices.

    Science.gov (United States)

    Morimoto, S; Miyawaki, N; Sasaki, Y; Matsumura, Y

    1986-06-01

    The effects of arotinolol on changes in renin release in rat kidney cortical slices in response to isoproterenol (IP) or norepinephrine (NE), were studied in comparison with those of AC-623, a main metabolite of arotinolol, and other typical adrenoceptor antagonists. Arotinolol, at concentrations of 10(-8) to 10(-4) mol/l, inhibited the increasing effect of 10(-6) mol/l IP on renin release, in a concentration-dependent manner. Similar results were observed with AC-623, propranolol or labetalol, although the inhibitory potencies of these agents were considerably lower than that of arotinolol. The blocking effect of arotinolol on the 10(-5) mol/l NE-induced decrease in renin release was much less potent than seen with other alpha-adrenoceptor blocking agents such as prazosin, phenoxybenzamine and labetalol. These data suggest that the potent blocking effects of arotinolol and its metabolite on the increased renin release in response to beta-adrenoceptor stimulation may contribute to the antihypertensive effect of this agent.

  8. Agonist-selective effects of opioid receptor ligands on cytosolic calcium concentration in rat striatal neurons.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Hooper, Robert; Dun, Nae J; Undieh, Ashiwel S; Adler, Martin W; Benamar, Khalid; Brailoiu, Eugen

    2012-06-01

    Buprenorphine is an opioid receptor ligand whose mechanism of action is incompletely understood. Using Ca(2+) imaging, we assessed the effects of buprenorphine, β-endorphin, and morphine on cytosolic Ca(2+) concentration [Ca(2+)](i), in rat striatal neurons. Buprenorphine (0.01-1 μM) increased [Ca(2+)](i) in a dose-dependent manner in a subpopulation of rat striatal neurons. The effect of buprenorphine was largely reduced by naloxone, a non-selective opioid receptor antagonist, but not by μ, κ, δ or NOP-selective antagonists. β-Endorphin (0.1 μM) increased [Ca(2+)](i) with a lower amplitude and slower time course than buprenorphine. Similar to buprenorphine, the effect of β-endorphin was markedly decreased by naloxone, but not by opioid-selective antagonists. Morphine (0.1-10 μM), did not affect [Ca(2+)](i) in striatal neurons. Our results suggest that buprenorphine and β-endorphin act on a distinct type/subtype of plasmalemmal opioid receptors or activate intracellular opioid-like receptor(s) in rat striatal neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of calcium chloride concentration on output force in electrical actuator made of sodium alginate gel

    Science.gov (United States)

    Wu, Yuda; Zhao, Gang; Wei, Chengye; Liu, Shuang; Fu, Yu; Liu, Xvxiong

    2018-01-01

    As a kind of artificial muscle intelligent material, the biological gel electric driver has the advantages of low driving voltage, large strain, good biological compatibility, good flexibility, low price, etc. The application prospect is broad and it has high academic value. Alginate, as a common substance in sea, has characteristics of low cost, green and pollution-free. Therefore,this paper obtains biological gel electric actuator by sodium alginate and calcium chloride. Effects on output force of the electric actuator is researched by changing the crosslinking of calcium chloride concentration and the output force enhancement mechanism is analyzed in this paper.

  10. Effect of calcium, magnesium and sodium ions on in vitro nucleation of human gall bladder bile.

    OpenAIRE

    Neithercut, W D

    1989-01-01

    The effect of increasing the calcium, magnesium and sodium concentration in gall bladder bile samples from 21 patients with gall stones and nine controls on the in vitro rate of formation of cholesterol microcrystals and numbers of cholesterol microcrystals formed was examined. Addition of these cations to raise the mean maximum concentration of calcium ions to 19.8 mmol/l, of magnesium ions to 20 mmol/l and sodium ions to 998 mmol/l did not trigger nucleation in control bile samples or sampl...

  11. Effect of calcium dobesilate on nephropathy in type 2 diabetic rats.

    Science.gov (United States)

    Liu, Xiaocheng; Liu, Xinming

    2005-01-01

    In order to investigate the effects and mechanisms of calcium dobesilate on renal lesions in experimental type 2 diabetic rats, dibetic rats were randomly divided into control group (group C) and experimental group (group D) treated with calcium dobesitate. The serum creatinine (Scr), protein kinase C (PKC), creatinine clearance (Ccr), transforming growth factor-beta, (TGF-beta1), type IV collagen were compared among the groups after 24 weeks. The renal tissues were observed under light microscopy and electron microscopy. The results showed that after 24 weeks, Scr, PKC, TGF-beta1 in group D were significantly lower than in group C, meanwhile, renal pathologic changes in group D were improved. Ccr had no difference between group C and group D. It was concluded that calcium dobesilate could ameliorate renal lesions in diabetic rats through inhibiting PKC and TGF-beta1.

  12. Aqueous solutions of calcium ions: hydration numbers and the effect of temperature.

    Science.gov (United States)

    Zavitsas, Andreas A

    2005-11-03

    Hydration numbers of calcium ions are determined from extensive measurements of colligative properties of water solutions of calcium salts. The hydration numbers reported refer to the average number of water molecules that are bound sufficiently strongly to calcium ions so as to be removed from the solvent and become part of the solute. Contrary to common descriptions of deviations from ideal behavior for concentrated solutions, ideal behavior is demonstrated when mole fractions are calculated by taking account of such bound water. Measurements over wide concentration and temperature ranges are used to obtain the effect of temperature on the average hydration number of Ca(2+). Freezing point depression measurements yield a hydration number of 12.0 +/- 0.8. Boiling point elevations yield 6.7 +/- 0.6. Consistent with this, vapor pressure measurements from 0 to 200 degrees C show a gradual decrease in hydration number with increasing temperature, with a value of 5.0 at 200 degrees C.

  13. Effect of Manganese on the Formation Mechanisms of Silico-Ferrite of Calcium and Aluminum (SFCA)

    Science.gov (United States)

    Xia, Leige; Li, Xinyu; Zhang, Jianliang; Yao, Chaoquan; Guo, Jian; Zhang, Chao

    In this research, analytical reagents were used for the sintering experiments. And the sinters were using X-ray diffraction, scanning electron microscope and mineralogical microscope analysis to study the effect mechanism of manganese on the silico-ferrite of calcium and aluminum (SFCA) bonding phase formation during the sintering process. The results indicated that the increasing content of manganese would greatly reduce the content of SFCA, and promote the formation of calcium aluminum silicate and the amount of pores and cracks. The existence of manganese inhibited the silicon form into the SFCA and a great deal of Fe2O3 was participated in the crystal transition to Fe3O4. When the ratio of the added manganese was less than 3% in the mixing, the calcium ferrite was in substantially interleaving corrosion with hematite and magnetite. Both the porosity and silicate glass phase content were low simultaneously, which contributed to the sintering production.

  14. Effects of extracellular calcium and sodium on depolarization-induced automaticity in guinea pig papillary muscle.

    Science.gov (United States)

    Katzung, B G

    1975-07-01

    Regenerative discharge of action potentials is induced in mammalian papillary muscles by passage of small depolarizing currents. In this paper, the effects of various extracellular calcium and sodium concentrations and of tetrodotoxin on this phenomenon were studied in guinea pig papillary muscles in a sucrose gap chamber. Phase 4 diastolic depolarization was found to be associated with an increase in membrane resistance. The slope of phase 4 depolarization was decreased by reductions in extracellular calcium or sodium concentration. The range of maximum diastolic potentials and the thresholds from which regenerative potentials arose were reduced, especially at the positive limit of potentials, by a reduction in either ion. It was concluded that both calcium and sodium influence diastolic depolarization and participate in the regenerative action potentials of depolarization-induced ventricular automaticity.

  15. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    Science.gov (United States)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  16. 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.

  17. 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.

  18. Effect of cadmium on the bioelement composition of Nostoc UAM208: Interaction with calcium

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Pinas, F.; Mateo, P.; Bonilla, I. [Universidad Autonoma de Madrid (Spain)

    1997-04-01

    Heavy metals may cause effects on the cyanobacterial cell including possible damage to the membranes and leakage from cells resulting in the loss or reduction of essential bioelements. There are many reports in the literature concerning morphological, biochemical and physiological changes caused by cadmium in cyanobacteria, but data on the influence of cadmium on the ion balance of the cell dealing with the interactive effect of cadmium and calcium are limited. Calcium has been found to exert a protective role against heavy metal toxicity in a variety of organisms, We previously reported that calcium is able to counteract the toxic effect of cadmium towards growth, photosynthesis, nitrogenase activity and pigment content of the cyanobacterium Nostoc UAM208. In the present study, we analyzed the content of essential ions, as affected by cadmium treatment, to search for possible mechanisms of heavy metal damage and toxicity in Nostoc. We also studied whether calcium enrichment (1.1 mM final concentration) has any influence on the heavy metal effect on those ionic contents. 13 refs., 2 figs.

  19. 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

  20. Effect of calcium bentonite on lipid parameters in Wistar albino rat ...

    African Journals Online (AJOL)

    The in vivo effect of Nigerian calcium bentonite clay on rat plasma cholesterol and triglyceride levels of Wistar albino rats was investigated. The rats were fed for a period of four weeks with varying concentrations of the bentonite clay, and the cholesterol and triglyceride levels determined using spectrophotometric methods.

  1. Effects of calcium paste as a seed coat on growth, yield and ...

    African Journals Online (AJOL)

    The present study was conducted to study the effect of coating the seeds with calcium paste before sowing, on plant growth, yield, the contents of some antioxidants and the activities of carbonic anhydrase and nitrate reductase in the Pisum sativum L. leaves under the influence of NaCl stress. NaCl stress reduced plant ...

  2. The effect of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts

    NARCIS (Netherlands)

    Yang, Liang; Perez-Amodio, Soledad; Barrère, F.; Everts, Vincent; van Blitterswijk, Clemens; 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,

  3. The effects of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts

    NARCIS (Netherlands)

    Yang, L.; Perez-Amodio, S.; Barrere-de Groot, F.Y.F.; Everts, V.; van Blitterswijk, C.A.; Habibovic, P.

    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,

  4. 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, pmemory, 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. © The Author(s) 2015.

  5. 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

  6. SKF 83959 is an antagonist of dopamine D1-like receptors in the prefrontal cortex and nucleus accumbens: a key to its antiparkinsonian effect in animals?

    Science.gov (United States)

    Cools, A R; Lubbers, L; van Oosten, R V; Andringa, G

    2002-02-01

    SKF 83959 that has a unique antiparkinson profile in animal models of Parkinson's disease is an in vitro dopamine D1 antagonist of receptors coupled to adenylyl cyclase. We hypothesized that SKF 83959, among others, interacts with dopamine D1 receptors coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. Effects of intra-accumbal injections of SKF 83959 on locomotor activity were compared to effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonist SCH 39166. Similarly to SCH 39166, SKF 83959 did not affect locomotor activity, but counteracted SKF 81297-induced locomotor activity. Effects of unilateral intra-prefrontal injections of SKF 83959 on rotational behaviour were compared to the effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonists SCH 23390 and SCH 39166 in rats selected on basis of their high locomotor response to novelty and pretreated with a subcutaneous injection of 0.75 mg/kg dexamphetamine. Like SCH 39166 and SCH 23390, SKF 83959 induced a bias for contralateral rotating and blocked the SKF 81297-induced bias for ipsilateral rotating. In conclusion, SKF 83959 is an in vivo antagonist of dopamine D1 receptors that are coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. The role of these receptors in the antiparkinson profile of SKF 83959 is discussed.

  7. Pharmacokinetic/pharmaco-dynamic modelling and simulation of the effects of different cannabinoid receptor type 1 antagonists on (9)-tetrahydrocannabinol challenge tests

    NARCIS (Netherlands)

    Guan, Zheng; Klumpers, Linda E.; Oyetayo, Olubukayo-Opeyemi; Heuberger, Jules; van Gerven, Joop M. A.; Stevens, Jasper

    Aim: The severe psychiatric side effects of cannabinoid receptor type 1 (CB1) antagonists hampered their wide development but this might be overcome by careful management of drug development with pharmacokinetic/pharmacodynamic (PK/PD) analyses. PK/PD models suitable for direct comparison of

  8. 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...

  9. Effect of supplementation with barley and calcium hydroxide on intake of Mediterranean shrubs

    Directory of Open Access Journals (Sweden)

    Dragan Skobic

    2011-04-01

    Full Text Available Maquis plant communities are one of the most varied vegetation types in the Mediterranean region and an important habitat for wild and domestic herbivores. Although the majority of these shrubs are nutritious, the secondary compounds are main impediments that reduce their forage value. In five experiments we determined the effect of supplementing goats with calcium hydroxide plus barley, and barley alone on intake of five dominant shrubs (Quercus ilex, Erica multiflora, Arbutus unedo, Viburnum tinus and Pistacia lentiscus of the Mediterranean maquis community. The combination of calcium hydroxide plus barley and barley alone increased utilization of all five investigated Mediterranean shrubs; therewith that intake of Arbutus unedo and Viburnum tinus was not statistically significant. Supplemented goats with calcium hydroxide plus barley or barley alone could be effective in controlling secondary compounds-rich Mediterranean shrubs where their abundance threatens biodiversity. This control can be facilitated by browsing dominant Mediterranean shrubs, which has been shown to be effective in managing Mediterranean maquis density. Calcium hydroxide and barley (energy enhance use of secondary compounds-containing plants, which may increase production of alternate forages and create a more diverse mix of plant species in the Mediterranean maquis plant community.

  10. Effects of an interleukin-1 receptor antagonist on human sleep, sleep-associated memory consolidation, and blood monocytes.

    Science.gov (United States)

    Schmidt, Eva-Maria; Linz, Barbara; Diekelmann, Susanne; Besedovsky, Luciana; Lange, Tanja; Born, Jan

    2015-07-01

    Pro-inflammatory cytokines like interleukin-1 beta (IL-1) are major players in the interaction between the immune system and the central nervous system. Various animal studies report a sleep-promoting effect of IL-1 leading to enhanced slow wave sleep (SWS). Moreover, this cytokine was shown to affect hippocampus-dependent memory. However, the role of IL-1 in human sleep and memory is not yet understood. We administered the synthetic IL-1 receptor antagonist anakinra (IL-1ra) in healthy humans (100mg, subcutaneously, before sleep; n=16) to investigate the role of IL-1 signaling in sleep regulation and sleep-dependent declarative memory consolidation. Inasmuch monocytes have been considered a model for central nervous microglia, we monitored cytokine production in classical and non-classical blood monocytes to gain clues about how central nervous effects of IL-1ra are conveyed. Contrary to our expectation, IL-1ra increased EEG slow wave activity during SWS and non-rapid eye movement (NonREM) sleep, indicating a deepening of sleep, while sleep-associated memory consolidation remained unchanged. Moreover, IL-1ra slightly increased prolactin and reduced cortisol levels during sleep. Production of IL-1 by classical monocytes was diminished after IL-1ra. The discrepancy to findings in animal studies might reflect species differences and underlines the importance of studying cytokine effects in humans. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis.

    Science.gov (United States)

    Laban, Kamil G; Vergouwen, Mervyn D I; Dijkhuizen, Rick M; Sena, Emily S; Macleod, Malcolm R; Rinkel, Gabriel J E; van der Worp, H Bart

    2015-07-01

    In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

  12. 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.

  13. Combined effect of antagonistic yeast and modified atmosphere to control Penicillium expansum infection in sweet cherries cv. Ambrunés.

    Science.gov (United States)

    de Paiva, E; Serradilla, M J; Ruiz-Moyano, S; Córdoba, M G; Villalobos, M C; Casquete, R; Hernández, A

    2017-01-16

    Fruit decay caused by pathogenic moulds is a major concern in the postharvest quality and shelf life of fruit. Blue mould decay is caused by Penicillium expansum (P. expansum) and is one of the most important postharvest diseases in cherries (Prunus avium L.). Synthetic fungicides are the main medium used to control pathogenic moulds. However, alternative approaches are available for developing safer technologies to control postharvest disease. An integrated approach that combines biological control, using antagonistic yeasts and modified atmosphere packaging (MAP) with cold storage is a promising alternative to synthetic fungicide treatment. In this work, two microperforated films (M10 and M50) and two antagonistic yeast strains (Hanseniaspora opuntiae L479 and Metschnikowia pulcherrima L672) were evaluated for their effectiveness to control the development of P. expansum in wounded cherries stored at 1°C. Results showed that the microperforated films had fungistatic effects, particularly M50, due to the level of CO2 achieved (mean CO2 of 11.2kPa at 35days), and the decrease in disease severity. Antagonistic yeasts, particularly Metschnikowia pulcherrima L672, delayed the development of P. expansum and decreased disease incidence and severity. The combination of MAP and antagonistic yeasts was the most effective approach to control P. expansum, during cold storage. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Effect of L- type Calcium Channel Blocker Nimodipine and T-type Calcium Channel Blocker Flunarizine on Motor Control in Mice

    Directory of Open Access Journals (Sweden)

    Swapnil Balkrishna Kaikade

    2015-05-01

    Full Text Available Objective: To study the effect of L-type of Calcium channel blocker nimodipine and T-type of calcium channel blocker funarizine on locomotor activity in mice without pretreatment by any other drug. Materials and method: The study was carried out following permission from the Institutional animal ethics committee. Healthy Swiss albino mice of either sex were selected by the strict inclusion and exclusion criteria and the grouping is done. Group A is control treated with normal saline, Group B and C received two titrated doses of nimodipine while Group D and E received two titrated doses of flunarizine. The animals were then observed for motor control on inclined plane and the Statistical analysis was done by using unpaired‘t’ test. Results: L-type calcium channel blocker nimodipine has dose dependent effect on motor control on inclined plane while the T- type calcium channel blocker flunarizine has no effect on motor control. Conclusion: Nimodipine has significant dose dependent depressant action on motor control on inclined plane while flunarizine has no effect on the above mentioned parameter.

  15. Calcium channel blockade limits cardiac remodeling and improves cardiac function in myocardial infarction-induced heart failure in rats

    NARCIS (Netherlands)

    Sandmann, S.; Claas, R.; Cleutjens, J. P.; Daemen, M. J.; Unger, T.

    2001-01-01

    Calcium channel antagonists (CCAs) have been proposed to prevent cardiac events after myocardial infarction (MI). However, unwanted effects, such as negative inotropy, limit their use in many cases. The aim of this study was to compare the effects of long-term treatment with the CCAs, mibefradil,

  16. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens.

    Science.gov (United States)

    Reissig, Chad J; Carter, Lawrence P; Johnson, Matthew W; Mintzer, Miriam Z; Klinedinst, Margaret A; Griffiths, Roland R

    2012-09-01

    Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Single, acute oral doses of DXM (100, 200, 300, 400, 500, 600, 700, and 800 mg/70 kg), triazolam (0.25 and 0.5 mg/70 kg), and placebo were administered to 12 healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 h. Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis; increases in observer-rated effects typical of classic hallucinogens (e.g., distance from reality, visual effects with eyes open and closed, joy, anxiety); and participant ratings of stimulation (e.g., jittery, nervous), somatic effects (e.g., tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70 kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g., psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow-up, volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin.

  17. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

    Science.gov (United States)

    Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2013-01-01

    Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

  18. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells.

    Science.gov (United States)

    AbdulQader, Sarah Talib; Kannan, Thirumulu Ponnuraj; Rahman, Ismail Ab; Ismail, Hanafi; Mahmood, Zuliani

    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 300μm and 65% porosity were prepared from phosphoric acid (H2PO4) and calcium carbonate (CaCO3) sintered at 1000°C for 2h. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Clinical effect of PRP combined with calcium dobesilate in treatment of patients with DR

    Directory of Open Access Journals (Sweden)

    Li-Bo Wang

    2017-09-01

    Full Text Available AIM: To investigate the clinical effect of panretinal photocoagulation(PRPcombined with calcium dobesilate in treatment of diabetic retinopathy(DR. METHODS: Selected 120 cases(240 eyesof DR diagnosed in our hospital from January 2011 to January 2016 were retrospectively analyzed. According to whether calcium dobesilate was used, the treatment group was divided into two groups. Sixty cases were treated with PRP combined with calcium dobesilate, and 60 cases in the control group were treated with PRP only. The BCVA, CMT and clinical efficacy of the two groups were compared. RESULTS: Before treatment, there was no significant difference on BCVA between combined group and control group(P>0.05. After treatment, BCVA of combined group was higher than that of the control group(PP>0.05; after treatment, the combination group on CMT, neovascularization and fluorescein leakage area value were less than the control group(PPCONCLUSION:PRP combined with calcium dobesilate in treatment of DR has a more significant clinical effect than PRP alone.

  20. 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.

  1. 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.

  2. Effect of timing of administered calcium lactate on the sucrose-induced intraoral demineralization of bovine enamel.

    Science.gov (United States)

    Kashket, S; Yaskell, T

    1992-03-01

    A number of soluble calcium salts are known to reduce the demineralization of enamel in the mouth. The present study was undertaken to examine the effects of rinses containing different concentrations of calcium lactate, and the time of giving the rinses with respect to sucrose challenges. Subjects wore palatal appliances containing blocks of bovine enamel whose surfaces were covered with Streptococcus mutans IB 1600, and rinsed with 10% sucrose for 1 min. Changes in iodide penetrability of the enamel, and the pH and extracellular ion concentrations of the streptococcal plaque were determined. When added to the sucrose rinse, 100 or 150 mM calcium lactate reduced demineralization by about 35%, although the plaque pH was not affected. Plaque calcium was elevated but diffused away rapidly so that concentrations after 45 min were close to control values. Plaque inorganic phosphate and lactate were not affected. Ongoing demineralization appeared to be stopped when 100 mM calcium lactate was given 15 min after the sucrose rinse. When the lactate was given 15 min before the sucrose rinse, demineralization was reduced by only about 25%, consistent with the rapid diffusion of plaque calcium. The combination of (i) pretreatment with calcium lactate and (ii) admixture of calcium lactate with sucrose was most effective. Demineralization was reduced about 55% with 100 mM calcium lactate under these conditions, and protective effects were seen with as little as 25 mM. In summary, the findings demonstrate the enamel-protective effect of relatively low concentrations of calcium lactate, and point to the need to sustain a high plaque calcium during periods of maximum acidogenicity.

  3. Isolation and molecular identification chitinase-producing Streptomyces strains and examination of their in-vitro antagonistic effects

    Directory of Open Access Journals (Sweden)

    Alireza Dehnad

    2015-12-01

    Full Text Available Introduction: The chemical fungicides are used widely in the world. To reduce the application of synthetic fungicides in treating plant diseases, biological methods are considered as an alternative way to control plant diseases. Many actinomycetes, particularly Streptomyces species are biological agents against a broad spectrum of fungal plant pathogens. The purpose of this study was using the kitinolitik actinomycetes isolated from soil of Eastern Azerbaijan province In order to produce biological pesticides. Materials and methods: Soil samples were taken from different areas of Eastern Azerbaijan province. According to Streptomyces morphological features, single colonies were isolated. To identify the bacteria by molecular characteristic, the genomic DNA was extracted and then the sequences of 16S rDNA were replicated. By using specific primers the bacterial isolates containing chitinase gene were screened. The isolates consisted Chitinase enzyme and were antagonistically cultured with Alternaria genus which is a fungal plant pathogen. Results: Out of 60 soil collected samples, 31 Streptomyces bacterial isolates were separated. Four isolates showed positive results to selectivity action of the chitinase enzyme. Treatment of 3 bacterial isolates with 2 pathogenic fungi showed that AE09 is the most effective anti-fungal isolates. Discussion and conclusion: Soils in Eastern Azerbaijan province are rich of Streptomyces bacteria which generate antifungal compounds. Obtaining the Streptomyces bacteria which have chitinase gene, can lead to identification of very effective strains as anti-fungal.

  4. Effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, on allograft arteriosclerosis after aortic transplantation in rats.

    Science.gov (United States)

    Watada, Susumu; Harada, Hirohisa; Matsubara, Kentaro; Obara, Hideaki; Matsumoto, Kenji; Ando, Nobutoshi; Kitagawa, Yuko

    2013-12-01

    Sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, is known to prevent serotonin-induced neointimal hyperplasia. We examined the effect of this agent on allograft arteriosclerosis in a rat model of aortic transplantation. Rats were given an aortic isograft or allograft and oral administration of either saline vehicle alone or 20mg/kg daily of sarpogrelate for 8 weeks. The grafts were then harvested, and the lumen diameter and the thickness of the intima and media were measured. Comparisons were made between measurement results in isografts and allografts from rats treated and not treated with sarpogrelate. Immunohistochemistry assessments were used to detect expression of serotonin in graft specimens. For both allografts and isografts, significantly less intimal thickening was observed in specimens from rats given sarpogrelate compared with rats given saline. Sarpogrelate had no effect on medial thickening in either graft type. Serotonin was detected in allografts from rats given saline alone but not in allografts from rats given sarpogrelate or in isografts. Sarpogrelate hydrochloride may mitigate arteriosclerosis in allografts. Platelet aggregation and serotonin may be correlated with intimal thickening associated with chronic rejection. © 2013. Published by Elsevier B.V. All rights reserved.

  5. Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure

    DEFF Research Database (Denmark)

    Kjekshus, John K; Torp-Pedersen, Christian; Gullestad, Lars

    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.......3, 3.2, P = 0.020), primarily through reduced end-systolic volume from 165 to 158 mL (P = 0.060). There was a trend for greater increase in LVEF (2.7%, CI -1.1, 6.6, P = 0.15) in a small subset of patients not on chronic beta-blocker therapy. There was no significant effect on neurohormones, quality...

  6. Calcium - urine

    Science.gov (United States)

    Urinary Ca+2; Kidney stones - calcium in urine; Renal calculi - calcium in your urine; Parathyroid - calcium in urine ... Urine calcium level can help your provider: Decide on the best treatment for the most common type of kidney ...

  7. Multitrophic effects of calcium availability on invasive alien plants, birds, and bird prey items

    Science.gov (United States)

    Vince D' Amico; Greg Shriver; Jake Bowman; Meg Ballard; Whitney Wiest; Liz Tymkiw; Melissa. Miller

    2011-01-01

    Acid rain alters forest soil calcium concentrations in two ways: (1) hydrogen ions displace exchangeable calcium adsorbed to soil surfaces, and (2) aluminum is released to soil water by acid rain and displaces adsorbed calcium. This increases the absorption of aluminum by plant roots, and decreases the absorption of calcium, causing calcium to be more readily leached...

  8. Synergistic and antagonistic effects of thermal shock, air exposure, and fishing capture on the physiological stress of Squilla mantis (Stomatopoda.

    Directory of Open Access Journals (Sweden)

    Saša Raicevich

    Full Text Available This study is aimed at assessing the effects of multiple stressors (thermal shock, fishing capture, and exposure to air on the benthic stomatopod Squilla mantis, a burrowing crustacean quite widespread in the Mediterranean Sea. Laboratory analyses were carried out to explore the physiological impairment onset over time, based on emersion and thermal shocks, on farmed individuals. Parallel field-based studies were carried out to also investigate the role of fishing (i.e., otter trawling in inducing physiological imbalance in different seasonal conditions. The dynamics of physiological recovery from physiological disruption were also studied. Physiological stress was assessed by analysing hemolymph metabolites (L-Lactate, D-glucose, ammonia, and H+, as well as glycogen concentration in muscle tissues. The experiments were carried out according to a factorial scheme considering the three factors (thermal shock, fishing capture, and exposure to air at two fixed levels in order to explore possible synergistic, additive, or antagonistic effects among factors. Additive effects on physiological parameters were mainly detected when the three factors interacted together while synergistic effects were found as effect of the combination of two factors. This finding highlights that the physiological adaptive and maladaptive processes induced by the stressors result in a dynamic response that may encounter physiological limits when high stress levels are sustained. Thus, a further increase in the physiological parameters due to synergies cannot be reached. Moreover, when critical limits are encountered, mortality occurs and physiological parameters reflect the response of the last survivors. In the light of our mortality studies, thermal shock and exposure to air have the main effect on the survival of S. mantis only on trawled individuals, while lab-farmed individuals did not show any mortality during exposure to air until after 2 hours.

  9. 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.

  10. Effectiveness of calcium lactate added to food in reducing intraoral demineralization of enamel.

    Science.gov (United States)

    Kashket, S; Yaskell, T

    1997-01-01

    Following the demonstration that rinses with solutions of soluble calcium salts reduced sucrose-induced demineralization, a study was undertaken to determine whether a similar effect could be obtained by the supplementation of a solid food with calcium lactate (CL). Subjects wore palatal appliances containing blocks of bovine enamel that were coated with Streptococcus mutans IB 1600 and ate 5-gram portions of cookies made with defined levels of CL. Determinations were made of changes in iodide penetrability (delta Ip) of the enamel, as well as the pH, calcium and inorganic phosphate of the streptococcal plaque. CL at 3.2% (w/w) reduced delta Ip from 12.9 +/- 1.7 to 6.1 +/- 0.9 units, i.e. by 52.7%. Plaque pH was not affected. Demineralization was reduced progressively with increasing concentrations of added CL, and CL was most effective with increasingly sweet cookies. Plaque contained 32.4 +/- 6.0 and 17.1 +/- 4.2 mM calcium after 1 and 5 min, respectively. Calculations showed that the plaque was saturated with respect to enamel during the first 5-10 minutes after food ingestion, in spite of the progressive drop in plaque pH. In conclusion, the present study demonstrated the reduction of the cariogenic potential of solid food by relatively low concentrations of CL. The effect appeared to be related to the ability of the food to maintain high levels of calcium in the streptococcal plaque during the period of active acidogenesis.

  11. Effect of Hypergravity on Localization Calcium Ions in Plant Cells Grown in Vivo and in Vitro

    Science.gov (United States)

    Nedukha, Olena

    Using plant callus tissues and Arabidopsis thaliana plants as model systems we have been investigated the effect of hypergravity on the localization and relative content of calcium ions in photosynthesizing cells. The tobacco callus cells in log stage of growth and mesophyll cells from developed A. thaliana leaves were used in the experiments. Plant samples were exposed to hypergravity at 6.5 g, 10g and 14 g for 15-60 min. After centrifugation, dye Fluo-4 was loaded in the control leaves and the centrifuged samples by the standard cytochemical method. Observation of calcium fluorescence was carried out with a laser confocal microscope LSM 5 Pascal at the excitation wave 488 nm (by the argon laser), at emission wavelength 516 nm. The data of the calcium ion distribution and quantification in cells were obtained using software "Pascal" (Carl Zeiss). The effect of hypergravity on redistribution of calcium ions in plant cells has been established. This effect is depended from exposure time and from the value of hypergravity. The cells cultivated in vitro is showed fast response to hypergravity influence. Plasmolysis cells and calcium domains formation have been observed in most of callus cells. This influence was like to that, which was wrote in Funaria hygrometrica protonema cells after 8.5 g influence (Sytnik et al., 1984). Leaf cells of A. thaliana were of less responsively to hypergravity than callus cells. Sytnik K, Kordyum E, Nedukha O. et al. 1984. Plant Cell Under Change of Geophysical Factors. Kiev: Naukova Dumka, 1-134 p.

  12. No Effect of Nutritional Adenosine Receptor Antagonists on Exercise Performance in the Heat

    Science.gov (United States)

    2008-11-01

    358–363, 1996. 11. Cook NC, Samman S. Flavonoids —chemistry, metabolism, cardiopro- tective effects, and dietary sources. Nutr Biochem 7: 66–76, 1996...metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother 51: 305–310, 1997. R400 ADENOSINE RECEPTOR ANTAGONISM AND EXERCISE IN THE HEAT...Interactions of flavonoids with adenosine receptors. J Med Chem 39: 781–788, 1996. 35. MacRae HS, Mefferd KM. Dietary antioxidant supplementation com

  13. Bone Mineral Density Accrual in Students with Autism Spectrum Disorders: Effects of Calcium Intake and Physical Training

    Science.gov (United States)

    Goodarzi, Mahmood; Hemayattalab, Rasool

    2012-01-01

    The purpose of this study was to investigate the effects of weight bearing exercise and calcium intake on bone mineral density (BMD) of students with autism spectrum disorders. For this reason 60 boy students with autism disorder (age 8-10 years old) were assigned to four groups with no differences in age, BMD, calcium intake, and physical…

  14. The effect of injectable calcium phosphate cement on bone anchorage of titanium implants: an experimental feasibility study in dogs.

    NARCIS (Netherlands)

    Arisan, V.; Anil, A.; Wolke, J.G.C.; Ozer, K.

    2010-01-01

    Calcium phosphate has high osteotransductive potential. The injectable form of calcium phosphate cement (ICAP) can be used as an adjunctive supportive agent for dental implants. The aim of this study was to assess the effect of an ICAP on the reverse torque resistance of titanium implants. Two

  15. Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice

    DEFF Research Database (Denmark)

    Refsgaard, Louise Konradsen; Pickering, Darryl S; Andreasen T., Jesper

    2017-01-01

    Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and anxiolytic-like actions, and cognitive and motor side effects of four NMDAR...... antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity...... test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty...

  16. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  17. 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.

  18. Noradrenergic α₁ receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Thomas F Newton

    Full Text Available Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic α(1 receptor antagonist doxazosin on the positive subjective effects of cocaine.Thirteen non-treatment seeking, cocaine-dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind.Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p<.001. Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p<.05. There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p<.10.Medications that block noradrenergic α₁ receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further.Clinicaltrials.gov NCT01062945.

  19. Effects of calcium fertilization and acid mist on calcium concentration and cold tolerance of red spruce needles

    Science.gov (United States)

    G. R. Strimbeck; David R. Vann; Arthur H. Johnson

    1996-01-01

    Several studies have shown that exposure to acid mist impairs cold tolerance of red spruce foliage, predisposing it to winter injury, which appears to be a major factor in the decline of montane populations of the species. Other studies have shown increases in calcium (Ca) concentration in canopy throughfall in montane spruce-fir forests, and decreases in foliar Ca...

  20. Effect of calcium-binding peptide from Pacific cod (Gadus macrocephalus) bone on calcium bioavailability in rats.

    Science.gov (United States)

    Peng, Zhe; Hou, Hu; Zhang, Kai; Li, Bafang

    2017-04-15

    Bone collagen peptide with high affinity to Ca was extracted from Pacific cod (Gadus macrocephalus) bone. FTIR spectra of calcium-binding bone collagen peptide showed that band at 3381cm(-1) shifted to 3361cm(-1), 1455cm(-1) moved to 1411cm(-1), and amide II became deeper valley, compared with that of bone collagen peptide. This peptide was sequenced by Q-TOF-MS and sequences of Gly-Pro-Glu-Gly, Gly-Glu-Lys, Gly-Pro-Leu-Gly and Gly-Leu-Pro-Gly appeared repeatedly in some peptides. From SEM, after chelated with calcium, the loose and porous structure turned into granular structure. From the animal experiment, Ca apparent absorption rate, Ca retention rate and femur Ca content of calcium-binding bone collagen peptide group were significantly higher than those of model and CaCO3 groups (P<0.05), while serum ALP was significantly lower than model group (P<0.05) and similar to control group. The results suggested that calcium-binding bone collagen peptide could improve bioavailability of Ca and thus prevented Ca deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Pulsed light and antimicrobial combination treatments for surface decontamination of cheese: Favorable and antagonistic effects.

    Science.gov (United States)

    Proulx, J; Sullivan, G; Marostegan, L F; VanWees, S; Hsu, L C; Moraru, C I

    2017-03-01

    Postprocessing cross-contamination of cheese can lead to both food safety issues and significant losses due to spoilage. Pulsed light (PL) treatment, consisting of short, high-energy, broad-spectrum light pulses, has been proven effective in reducing the microbial load on cheese surface. As PL treatment effectiveness is limited by light-cheese interactions, the possibility to improve its effectiveness by combining it with the antimicrobial nisin was explored. The effect of natamycin, which is added to cheeses as an antifungal agent, on PL effectiveness was also investigated. Pseudomonas fluorescens, Escherichia coli ATCC 25922, and Listeria innocua were used as challenge microorganisms. Bacterial cultures in stationary growth phase were diluted to initial inoculum levels of 5 or 7 log cfu per cheese slice. Slices of sharp white Cheddar cheese and white American singles were cut in rectangles of 2.5 × 5 cm. For cheese slices receiving antimicrobial treatment before PL, slices were dipped in natamycin or nisin, spot inoculated with 100 μL of bacterial suspension, and then treated with PL. Cheese slices receiving PL treatment before antimicrobials were spot inoculated, treated with PL, and then treated with antimicrobials. The PL fluence levels from 1.02 to 12.29 J/cm 2 were used. Survivors were enumerated by standard plate counting or the most probable number technique, as appropriate. All treatments were performed in triplicate, and the data were analyzed using a general linear model. Treatment with nisin or natamycin before PL decreased the effectiveness of PL for all bacteria tested. For instance, PL reduced P. fluorescens on Cheddar cheese by 2.19 ± 0.27 log after 6.14 J/cm 2 , whereas combination treatments at the same PL fluence yielded barely 1 log reduction. Inactivation of L. innocua on Cheddar was only 0.78 ± 0.01 log when using PL after nisin, compared with a 1.30 ± 0.76 log reduction by nisin alone. This was attributed to the absorption of UV light

  2. Effects of dietary crude protein and calcium/ phosphorus content on ...

    African Journals Online (AJOL)

    This experiment was conducted to examine the effect of three levels of crude protein (CP) (NRC, 15% more than NRC and 15% less than NRC) and three levels of Ca and available P (Av. P) (NRC, 15% more than NRC ... There was an interactive effect of CP by Ca and Av. P on the retention of Ca, N and ash of tibia bone.

  3. Differential effects of thapsigargin analogues on apoptosis of prostate cancer cells: complex regulation by intracellular calcium.

    Science.gov (United States)

    Dubois, Charlotte; Vanden Abeele, Fabien; Sehgal, Pankaj; Olesen, Claus; Junker, Steffen; Christensen, Søren B; Prevarskaya, Natalia; Møller, Jesper V

    2013-11-01

    The inhibition of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) by thapsigargin (Tg) and Tg-type analogues is considered to trigger cell death by activation of apoptotic pathways. Some of these analogues may be useful as antineoplastic agents after appropriate targeting as peptide conjugated prodrugs to cancer cells. With this in mind, this study evaluates the effect on LNCaP androgen-sensitive cancer cells of thapsigargin substituted with 12-aminododecanoyl linkers and Leu (Leu-8ADT), aspartate (Asp-8ADT) or Boc-8ADT. Our results show that both Leu-8ADT and Asp-8ADT result in rapid ER calcium depletion and an influx of calcium across the plasma membrane by activation of store-operated calcium entry. By contrast, ER Ca(2+) depletion by Boc-8ADT is a very slow process that does not perceptibly increase cytosolic Ca(2+) and activate store-operated calcium entry, because the inhibition of SERCA with this compound is very slow. Nevertheless, we find that Boc-8ADT is a more efficient inducer of apoptosis than both Tg and Leu-8ADT. Compared with Tg and the other analogues, apoptosis induced by Asp-8ADT is very modest, although this compound also activates store-operated calcium entry and at high concentrations (1 μm) causes severe morphological changes, reflecting decreased cell viability. We conclude that many factors need to be considered for optimization of these compounds in antineoplastic drug design. Among these ER stress induced by Ca(2+) endoplasmic reticulum mobilization seems particularly important, whereas the early cytosolic increase of Ca(2+) concentration preceding the executive phase of apoptosis appears to be of no, or little, consequence for a subsequent apoptotic effect. © 2013 FEBS.

  4. Effect of calcium hydroxide on ph changes of the external medium after intracoronal bleaching.

    Science.gov (United States)

    Sa, Patricia Marra de; Jeronymo, Raffaela Di Iorio; Yui, Karen Cristina Kazue; Silva, Eduardo Galera da; Huhtala, Maria Filomena Rocha Lima; Torres, Carlos Rocha Gomes; Gomes, Ana Paula Martins

    2011-05-01

    This in vitro study evaluated the effect of calcium hydroxide on pH changes of the external medium after intracoronal bleaching. A total of 50 extracted human premolars were prepared and filled with gutta-percha and endodontic sealer. The teeth were randomly divided into five groups according to the bleaching agents employed: (a) Sterile cotton pellet with distilled water (control group); (b) sodium perborate and distilled water; (c) sodium perborate and 10% carbamide peroxide; (d) sodium perborate and 35% hydrogen peroxide; (e) 35% hydrogen peroxide. The teeth were stored in vials containing distilled water and the pH values of the medium surrounding the teeth were analyzed. After 7-day storage, the bleaching agent was removed and replaced by calcium hydroxide, and the distilled water was changed, in which the teeth were kept stored for further 14 days. Measurement of pH of the external medium (distilled water) was performed 7 days after insertion of the bleaching agents, immediately, 7 and 14 days after insertion of the calcium hydroxide. Data were submitted to statistical analysis by the two-way ANOVA and Tukey,s test. There were pH changes of the external medium at 7- day period after bleaching procedures. These results confirmed the diffusion of bleaching agents to the external medium. Calcium hydroxide increased the external medium pH and was effective for pH alkalinization after intracoronal bleaching. Intracoronal bleaching of endodontically treated teeth may cause cervical root resorption. A possible explanation for this process is the passage of bleaching agents to the periodontal tissues yielding an inflammatory process. In an attempt to keep the neutrality of the periodontal pH, the calcium hydroxide has been recommended.Results of this study showed that this material should be always used after intracoronal bleaching.

  5. [Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney].

    Science.gov (United States)

    Gao, Mei-Juan; Liu, Ming; Li, Bo; Li, Ming-Long; Bian, Li-Xiang; Yu, Gui-Na

    2009-02-01

    The aim of this study is to study the effect of calcium dobesilate on streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male Wistar rats were randomly divided into six groups: normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x kg(-1) group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of kidney were examined with immunohistochemical staining. The endothelin (ET) in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways.

  6. Endoplasmic reticulum stress in pathogenesis of diabetic retinopathy and effect of calcium dobesilate

    Directory of Open Access Journals (Sweden)

    Yu-Min Gui

    2016-06-01

    Full Text Available 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.

  7. Effects of calcium dobesilate on glomerulus TIMP1 and collagen IV of diabetic rats.

    Science.gov (United States)

    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.

  8. Synergistic effect of calcium and bicarbonate in enhancing arsenate release from ferrihydrite

    Science.gov (United States)

    Saalfield, Samantha L.; Bostick, Benjamin C.

    2010-09-01

    Many groundwater systems contain anomalously high arsenic concentrations, associated with less than expected retention of As by adsorption to iron (hydr)oxides. Although carbonates are ubiquitous in aquifers, their relationship to arsenate mobilization is not well characterized. This research examines arsenate release from poorly crystalline iron hydroxides in abiotic systems containing calcium and magnesium with bicarbonate under conditions of static and dynamic flow (pH 7.5-8). Aqueous arsenic levels remained low when arsenate-bearing ferrihydrite was equilibrated with artificial groundwater solution containing Ca, Mg, and HCO 3-. In batch titrations in which a solution of Ca and HCO 3- was added repeatedly, the ferrihydrite surface became saturated with adsorbed Ca and HCO 3-, and aqueous As levels increased by 1-2 orders of magnitude. In columns containing Ca or Mg and HCO 3-, As solubility initially mimicked titrations, but then rapidly increased by an additional order of magnitude (reaching 12 μM As). Separately, calcium chloride and other simple salts did not induce As release, although sodium bicarbonate and lactate facilitated minor As release under flow. Results indicate that adsorption of calcium or magnesium with bicarbonate leads to As desorption from ferrihydrite, to a degree greater than expected from competitive effects alone, especially under dynamic flow. This desorption may be an important mechanism of As mobilization in As-impacted, circumneutral aquifers, especially those undergoing rapid mineralization of organic matter, which induces calcite dissolution and the production of dissolved calcium and bicarbonate.

  9. Simvastatin Effect on Calcium and Silicon Plasma Levels in Postmenopausal Women with Osteoarthritis.

    Science.gov (United States)

    Horecka, Anna; Hordyjewska, Anna; Blicharski, Tomasz; Kocot, Joanna; Żelazowska, Renata; Lewandowska, Anna; Kurzepa, Jacek

    2016-05-01

    Postmenopausal women more often suffered from knee osteoarthritis and its pathogenesis still remains unclear. Calcium and silicon are significant elements involved in bone and joint metabolism, especially in older people. Cardiovascular diseases are common worldwide and simvastatin is the most prescribed drug in such population of patients. The purpose of this study was to evaluate the effect of simvastatin administration on calcium and silicon concentration in the plasma of postmenopausal women with osteoarthritis. Sixty postmenopausal mild hypercholesterolemic women (mean age 61.4 years, range 54-68) were enrolled. Thirty patients received simvastatin (20 or 40 mg/day) for at least 1 year before being enrolled (simvastatin "+" group). Control group consists of remaining 30 women (simvastatin "-"group). Silicon and calcium concentrations were measured spectrophotometrically. Plasma simvastatin level was determined 3 h after the drug administration using HPLC-UV-Vis. Calcium but not silicon level was significantly lower in patients receiving simvastatin in comparison with non-statin group (1.91 ± 0.32 vs. 2.33 ± 0.19 mmol/l, p osteoarthritis treatment.

  10. Effect of feeding calcium salts on performance of nursing Awassi ewes.

    Science.gov (United States)

    Obeidat, Belal S; Awawdeh, Mofleh S; Titi, Hosam H; AbuGhazaleh, Amer A; Al-Lataifeh, Fatima A; Alawneh, Ibrahim A; Abu Ishmais, Majdi A; Qudsieh, Rasha I; Subih, Hadil S

    2011-08-01

    Twenty nursing Awassi ewes (BW = 50 ± 2.35 kg, age = 4.5 ± 1.2 years) with their lambs were used to evaluate the effects of feeding calcium salts in lactation diets on performance and pre-weaning growth of their lambs. Treatments were 0% calcium salts (CON) or 5% calcium salts (FAT). At the end of the study, a digestibility experiment was performed. Milk yield was greater (P Milk composition was similar (P > 0.05) between diets. However, milk energy value (kcal/day) tended to be greater (P = 0.07) for the FAT diet than the CON diet. Concentrations of milk C18:1c9 and C20:0 were greater (P  0.05) for diets. For lambs, weaning weight was not affected by treatments. However, average daily gain and total gain were greater (P = 0.053) for the FAT diet than the CON diet. Results suggest that supplementing lactating ewes with calcium salts at the beginning of lactation phase improves daily milk yield of ewes and pre-weaning growth of their lambs with no major negative impact on feed intake and digestibility.

  11. Aggregation of a Cationic Gemini Surfactant with a Chelating Molecule and Effects from Calcium Ions.

    Science.gov (United States)

    Zhao, Weiwei; Song, Kai; Chen, Yao; Wang, Hua; Liu, Zhang; Shi, Qiang; Huang, Jianbin; Wang, Yilin

    2017-11-07

    The aggregation behavior of cationic ammonium gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12) with chelating molecule ethylenediaminetetraacetic acid (EDTA) and the effects of calcium bromide (CaBr2) on the structure and morphology of the aggregates in the mixture have been investigated by surface tension, isothermal titration microcalorimetry, electrical conductivity, ζ potential, dynamic light scattering, cryogenic transmission electron microscopy, freeze-fracture transmission electron microscopy, and 1H NMR techniques. It was found that the electrostatic attraction between the carboxyl groups of EDTA and the headgroups of 12-6-12 leads to the formation of oligomeric-like surfactant EDTA(12-6-12)2 at an EDTA/12-6-12 molar ratio of 0.50. The critical aggregation concentration of the EDTA(12-6-12)2 complexes is much lower than that of 12-6-12, and the complexes form loose, large network-like premicellar aggregates and then transfer into small micelles with an increase in concentration. Moreover, the addition of CaBr2 induces the transition from the loose aggregates and micelles to vesicles owing to the coordination interaction between the calcium ion and EDTA and the electrostatic interaction between EDTA and 12-6-12. The work reveals that as a bridging molecule between the calcium ion and the gemini surfactant, the chelating molecule greatly promotes the assembly of the gemini surfactant and strengthens the molecular packing in the presence of calcium ions.

  12. Potential effects of ocean acidification on Alaskan corals based on calcium carbonate mineralogy composition analysis (NCEI Accession 0157223)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This archival package contains potential effects of ocean acidification on Alaskan corals based on calcium carbonate mineralogy composition analysis. Effects of...

  13. Effect of calcium on the kinetics of free fatty acid release during in vitro lipid digestion in model emulsions.

    Science.gov (United States)

    Ye, Aiqian; Cui, Jian; Zhu, Xiangqian; Singh, Harjinder

    2013-08-15

    The effects of different calcium salts on in vitro lipid digestion were examined by determining the free fatty acids released from various oil-in-water emulsions. The kinetics of the total and individual free fatty acids released by lipolysis were monitored by the pH-stat method and gas chromatography, respectively. The rate and the extent of free fatty acid release increased with an increase in the added calcium concentration, but the increase was dependent on the emulsifying agent. The effect of calcium was diminished when the emulsion contained phosphate. Soluble calcium salts, such as calcium gluconate, calcium acetate and CaCl2, had greater effects on the rate and extent of free fatty acid release than did insoluble salts, such as CaO and CaSO4, suggesting that the ionic state of calcium plays a critical role in lipid digestion in emulsions. The addition of calcium did not alter the profiles of the individual free fatty acids released. This study provides useful information for food formulation with respect to lipid digestion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Isolation of Antagonistic Endophytes from Banana Roots against Meloidogyne javanica and Their Effects on Soil Nematode Community

    Directory of Open Access Journals (Sweden)

    Lanxi Su

    2017-10-01

    Full Text Available Banana production is seriously hindered by Meloidogyne spp. all over the world. Endophytes are ideal candidates compared to pesticides as an environmentally benign agent. In the present study, endophytes isolated from banana roots infected by Meloidogyne spp. with different disease levels were tested in vitro, and in sterile and nature banana monoculture soils against Meloidogyne javanica. The proportion of antagonistic endophytes were higher in the roots of middle and high disease levels. Among those, bacteria were dominant, and Pseudomonas spp., Bacillus spp. and Streptomyces spp. showed more abundant populations. One strain, named as SA, with definite root inner-colonization ability was isolated and identified as Streptomyces sp. This strain showed an inhibiting rate of >50% in vitro and biocontrol efficiency of 70.7% in sterile soil against Meloidogyne javanica, compared to the control. Greenhouse experiment results showed that the strain SA exhibits excellent biological control ability for plant-parasites both in roots and in root-knot nematode infested soil. SA treatment showed a higher number of bacterivores, especially Mesorhabditis and Cephalobus. The maturity index was significantly lower, while enrichment index (EI was significantly higher in the SA treatment. In conclusion, this study presents an important potential application of the endophytic strain Streptomyces sp. for the control of plant-parasitic nematodes, especially Meloidogyne javanica, and presents the effects on the associated variation of the nematode community.

  16. Isolation of Antagonistic Endophytes from Banana Roots against Meloidogyne javanica and Their Effects on Soil Nematode Community.

    Science.gov (United States)

    Su, Lanxi; Shen, Zongzhuan; Ruan, Yunze; Tao, Chengyuan; Chao, Yifan; Li, Rong; Shen, Qirong

    2017-01-01

    Banana production is seriously hindered by Meloidogyne spp. all over the world. Endophytes are ideal candidates compared to pesticides as an environmentally benign agent. In the present study, endophytes isolated from banana roots infected by Meloidogyne spp. with different disease levels were tested in vitro, and in sterile and nature banana monoculture soils against Meloidogyne javanica. The proportion of antagonistic endophytes were higher in the roots of middle and high disease levels. Among those, bacteria were dominant, and Pseudomonas spp., Bacillus spp. and Streptomyces spp. showed more abundant populations. One strain, named as SA, with definite root inner-colonization ability was isolated and identified as Streptomyces sp. This strain showed an inhibiting rate of >50% in vitro and biocontrol efficiency of 70.7% in sterile soil against Meloidogyne javanica, compared to the control. Greenhouse experiment results showed that the strain SA exhibits excellent biological control ability for plant-parasites both in roots and in root-knot nematode infested soil. SA treatment showed a higher number of bacterivores, especially Mesorhabditis and Cephalobus. The maturity index was significantly lower, while enrichment index (EI) was significantly higher in the SA treatment. In conclusion, this study presents an important potential application of the endophytic strain Streptomyces sp. for the control of plant-parasitic nematodes, especially Meloidogyne javanica, and presents the effects on the associated variation of the nematode community.

  17. Effect of serum interleukin-1 receptor antagonist level on survival of patients with non-small cell lung cancer.

    Science.gov (United States)

    Yigit, Murat; Değirmencioğlu, Serkan; Ugurlu, Erhan; Yaren, Arzu

    2017-05-01

    Due to poor prognosis in advanced non-small cell lung cancer (NSCLC), new effective markers are required in the monitoring of the disease. The present study aimed to investigate the association between the serum IL-1 receptor antagonist (IL-1Ra) level, overall survival (OS), and treatment response in NSCLC, and to evaluate the usefulness of the serum IL-1Ra level as a prognostic marker for NSCLC. Eighty patients (72 men and 8 women) and 40 healthy volunteers (13 men and 27 women) were included in the present study. The median progression-free survival was 16 weeks for patients with high serum IL-1Ra levels, and 35 weeks for patients with low serum IL-1Ra levels (P=0.027). The median OS was 38 weeks in patients with a high serum IL-1Ra level, and 62 weeks in patients with a low serum IL-1Ra level (P=0.065). The results of the present study have demonstrated that there was a significant correlation between IL-1Ra levels and NSCLC progression and survival, although the correlation between IL-1Ra levels and the response to treatment was not statistically significant. Therefore, the pre-treatment IL-1Ra level has been identified as a putative prognostic factor for NSCLC.

  18. Long-term effects of amlodipine and lisinopril on left ventricular mass and diastolic function in elderly, previously untreated hypertensive patients : the ELVERA trial

    NARCIS (Netherlands)

    Terpstra, WF; May, JF; Smit, AJ; De Graeff, PA; Havinga, TK; van den Veur, E; Schuurman, FH; Meyboom-de Jong, B; Crijns, HJGM

    Objective To compare the effects of a calcium antagonist (amlodipine) and an angiotensin converting enzyme inhibitor (lisinopril) on left Ventricular mass and diastolic function in elderly, previously untreated hypertensives. Design A double-blind randomized parallel group trial. Effects of

  19. 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

    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......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...... 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...

  20. Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

    Science.gov (United States)

    Jara, Aquiles; von Höveling, Andrea; Jara, Ximena; Burgos, M Eugenia; Valdivieso, Andres; Mezzano, Sergio; Felsenfeld, Arnold J

    2006-04-01

    A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (Prats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (Phyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (Prats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (Prats on

  1. In-vitro antimicrobial activity and synergistic/antagonistic effect of interactions between antibiotics and some spice essential oils.

    Science.gov (United States)

    Toroglu, Sevil

    2011-01-01

    Spices and herbs have been used for many years by different cultures. The aim of the present study is (1) to investigate in-vitro antimicrobial effects of different spices and herbs (5 species: Rosmarinus officinalis (Rosemary), Coriandrum sativum (coriander), Micromeria fruticosa (L.) Druce subsp. Brachycalyx P.H. Davis (White micromeria), Cumium cyminum (cumin), Mentha piperita (Peppermint) against different bacteria and fungi species, and (2) to discuss the in-vitro possible effects between the plants and antibiotics. The microorganisms used were Micrococcus luteus LA 2971, Bacillus megaterium NRS, Bacillus brevis FMC 3, Enterococcus faecalis ATCC 15753, Pseudomonas pyocyaneus DC 127, Mycobacterium smegmatis CCM 2067, Escherichia coil DM, Aeromonas hydrophila ATCC 7966, Yersinia enterocolitica AU 19, Staphylococcus aureus Cowan 1, Streptococcus faecalis DC 74 bacteria, and Saccharomyces cerevisiae WET 136, Kluvyeromyces fragilis DC 98 fungi in this study. The results indicated that essential oils of Rosmarinus officinalis, Coriandrum sativum L., Micromeria fruticosa (L.) Druce subsp. brachycalyx P.H. Davis, Cumium cyminum L., Mentha piperita L. were shown antimicrobial activity in the range of 7-60 mm 2 microl(-1) inhibition zone to the microorganisms tested, using disc diffusion method. Standard antibiotic such as Gentamicin (10 microg), Cephalothin (30 microg), Ceftriaxone (10 microg), Nystatin (10 U) discs were used for comparison with the antimicrobial activities of essential oils of these plants. In addition, antibacterial activity of essential oils of these plants was researched by effects when it was used together with these standard antibiotics in vitro. However, antibacterial activity changed also by in vitro interactions between these standard antibiotics and essential oils of these plants. Synergic, additive or antagonist effects were observed in antibacterial activity.

  2. Effect of chronic delivery of the Toll-like receptor 4 antagonist (+)-naltrexone on incubation of heroin craving.

    Science.gov (United States)

    Theberge, Florence R; Li, Xuan; Kambhampati, Sarita; Pickens, Charles L; St Laurent, Robyn; Bossert, Jennifer M; Baumann, Michael H; Hutchinson, Mark R; Rice, Kenner C; Watkins, Linda R; Shaham, Yavin

    2013-04-15

    Recent evidence implicates toll-like receptor 4 (TLR4) in opioid analgesia, tolerance, conditioned place preference, and self-administration. Here, we determined the effect of the TLR4 antagonist (+)-naltrexone (a μ-opioid receptor inactive isomer) on the time-dependent increases in cue-induced heroin seeking after withdrawal (incubation of heroin craving). In an initial experiment, we trained rats for 9 hours per day to self-administer heroin (.1 mg/kg/infusion) for 9 days; lever presses were paired with a 5-second tone-light cue. We then assessed cue-induced heroin seeking in 30-minute extinction sessions on withdrawal day 1; immediately after testing, we surgically implanted rats with Alzet minipumps delivering (+)-naltrexone (0, 7.5, 15, 30 mg/kg/day, subcutaneous) for 14 days. We then tested the rats for incubated cue-induced heroin seeking in 3-hour extinction tests on withdrawal day 13. We found that chronic delivery of (+)-naltrexone via minipumps during the withdrawal phase decreased incubated cue-induced heroin seeking. In follow-up experiments, we found that acute injections of (+)-naltrexone immediately before withdrawal day 13 extinction tests had no effect on incubated cue-induced heroin seeking. Furthermore, chronic delivery of (+)-naltrexone (15 or 30 mg/kg/day) or acute systemic injections (15 or 30 mg/kg) had no effect on ongoing extended access heroin self-administration. Finally, in rats trained to self-administer methamphetamine (.1 mg/kg/infusion, 9 hours/day, 9 days), chronic delivery of (+)-naltrexone (30 mg/kg/day) during the withdrawal phase had no effect on incubated cue-induced methamphetamine seeking. The present results suggest a critical role of TLR4 in the development of incubation of heroin, but not methamphetamine, craving. Published by Elsevier Inc.

  3. 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.

  4. Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

    Science.gov (United States)

    Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B

    2015-01-01

    We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

  5. Hall effect in amorphous calcium-aluminum alloys

    Science.gov (United States)

    Mayeya, F. M.; Howson, M. A.

    1994-02-01

    We present results of the Hall effect measurements in CaAl(Au) amorphous alloys. The Hall coefficients have been found to be negative and independent of temperature. Their magnitudes deviate significantly from the nearly-free-electron calculations, and are reduced by gold doping. These deviations have been accounted for from considerations of the unusual electronic structure of CaAl, and the effects of both s-d hybridization and side-jump mechanism on the conduction electrons.

  6. 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......The disease mechanisms underlying dystrophin-deficient muscular dystrophy are complex, involving not only muscle membrane fragility, but also dysregulated calcium homeostasis. Specifically, it has been proposed that calcium channels directly initiate a cascade of pathological events by allowing...... 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...

  7. Short- and long-term effects of IL-1 and TNF antagonists on periodontal wound healing.

    Science.gov (United States)

    Zhang, Xuemei; Kohli, Malika; Zhou, Qingde; Graves, Dana T; Amar, Salomon

    2004-09-01

    The present study tested the effects of local injection of IL-1 and TNF soluble receptors on a periodontal wound-healing model in nonhuman primates. In this model, periodontal lesions were developed for 16 wk, followed by open flap surgery. Starting at the time of surgery, groups of animals received localized injections of both soluble cytokine receptors or else PBS three times per week for 3, 14, or 35 days. Periodontal wound healing was analyzed for each group at the end of the treatment regimen. Fourteen days after surgery, a significant decrease was observed between the animals treated with soluble receptors and the untreated group with respect to recruitment of inflammatory cells in deep gingival connective tissue. Concurrent apoptosis of inflammatory cells in those tissues increased significantly in treated animals compared with untreated animals. All other outcome parameters of periodontal wound healing were likewise significantly improved in treated animals compared with untreated animals. In marked contrast, however, 35 days after surgery, there was a significant increase in the number of inflammatory cells that had infiltrated into deep gingival connective tissue in treated compared with untreated animals. Outcome parameters of periodontal wound healing worsened in treated animals when compared with untreated. These results indicate that proinflammatory cytokines may play different functional roles in early vs late phases of periodontal wound healing. Short-term blockade of IL-1 and TNF may facilitate periodontal wound healing, whereas prolonged blockade may have adverse effects.

  8. Effect of soil-spraying time on root-colonization ability of antagonistic Streptomyces griseoviridis

    Directory of Open Access Journals (Sweden)

    H. KORTEMAA

    2008-12-01

    Full Text Available The root-colonization ability of Streptomyces griseoviridis Anderson et al. was tested on turnip rape (Brassica rapa subsp. oleifera DC. and carrot (Daucus carota L. by the sand-tube method. Non-sterile sand was sprayed with a microbial suspension immediately or 7 days after the seed had been sown. Results expressed as population frequencies and densities indicated that S. griseoviridis effectively colonizes the rhizosphere when the microbe is applied immediately after sowing but less effectively when it is applied 7 days later. Detection values of S. griseoviridis were higher for turnip rape than for carrot. In sterile sand, S. griseoviridis invaribly colonized the rhizosphere of turnip rape after each of the two applications. These findings indicate that S. griseoviridis can compete with indigenous soil microbes in the rhizosphere if it is sufficiently abundant in the soil before the seed emerges. If applied later, however, it competes rather poorly. In root-free nonsterile sand, S. griseoviridis dispersed and survived well.;

  9. Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b).

    Science.gov (United States)

    Yu, Qin-Wei; Hu, Jie; Wang, Hao; Chen, Xin; Zhao, Fang; Gao, Peng; Yang, Qiu-Bin; Sun, Dan-Dan; Zhang, Lu-Yong; Yan, Ming

    2016-05-01

    The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Calcium signaling induced by angiotensin II in the pancreatic acinar cell line AR42J.

    Science.gov (United States)

    Barnhart, D C; Sarosi, G A; Romanchuk, G; Mulholland, M W

    1999-03-01

    The purpose of this study was to characterize the nature and mechanisms of angiotensin II-evoked calcium signaling in AR42J cells. Cytosolic calcium concentrations were determined using fura-2-based microfluorimetry. Angiotensin II causes elevations in free cytosolic calcium ([Ca2+]i) in the rat pancreatic acinar cell line AR42J. The mechanisms of angiotensin II-evoked calcium signaling were examined using fura-2-based fluorescent digital microscopy. Angiotensin II caused dose-dependent increments in [Ca2+]i over a concentration range of 0.1-1,000 nM, with an average increment of 243 +/- 16 nM at an angiotensin II concentration of 1,000 nM. Dup753, an AT1-specific antagonist, inhibited angiotensin II-evoked signaling, whereas the AT2 antagonist PD123,319 had no effect. Preincubation with the phospholipase C inhibitor U73122 reduced the response in [Ca2+]i to 25% of that of the control. Thapsigargin abolished angiotensin II-evoked calcium signaling. The inositol 1,4,5-trisphosphate receptor antagonist heparin introduced by radiofrequency electroporation inhibited responses to 46 +/- 6% of controls. Angiotensin II-evoked signals were reduced in magnitude and duration by elimination of Ca2+ from the extracellular buffer. Preincubation with pertussis toxin (100 ng/ml) had no effect. Angiotensin II did not stimulate cyclic AMP or suppress vasoactive intestinal peptide stimulated cyclic AMP production over the concentration range that caused Ca2+ signaling.

  11. Antagonist effect of triptolide on AKT activation by truncated retinoid X receptor-alpha.

    Directory of Open Access Journals (Sweden)

    Na Lu

    Full Text Available BACKGROUND: Retinoid X receptor-alpha (RXRα is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXRα resulted in production of a truncated product, tRXRα, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K/AKT pathway. However, how the tRXRα-mediated signaling pathway in cancer cells is regulated remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened a natural product library for tRXRα targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXRα-mediated cancer cell survival pathway in vitro and in animals. Our results reveal that triptolide strongly induces cancer cell apoptosis dependent on intracellular tRXRα expression levels, demonstrating that tRXRα serves as an important intracellular target of triptolide. We show that triptolide selectively induces tRXRα degradation and inhibits tRXRα-dependent AKT activity without affecting the full-length RXRα. Interestingly, such effects of triptolide are due to its activation of p38. Although triptolide also activates Erk1/2 and MAPK pathways, the effects of triptolide on tRXRα degradation and AKT activity are only reversed by p38 siRNA and p38 inhibitor. In addition, the p38 inhibitor potently inhibits tRXRα interaction with p85α leading to AKT inactivation. Our results demonstrate an interesting novel signaling interplay between p38 and AKT through tRXRα mediation. We finally show that targeting tRXRα by triptolide strongly activates TNFα death signaling and enhances the anticancer activity of other chemotherapies. CONCLUSIONS/SIGNIFICANCE: Our results identify triptolide as a new xenobiotic regulator of the tRXRα-dependent survival pathway and provide new insight into the mechanism by which triptolide acts to induce apoptosis of cancer cells. Triptolide represents one of the most

  12. Effects of the 5-HT₆ receptor antagonists SB-399885 and RO-4368554 and of the 5-HT(2A) receptor antagonist EMD 281014 on sleep and wakefulness in the rat during both phases of the light-dark cycle.

    Science.gov (United States)

    Monti, Jaime M; Jantos, Héctor

    2011-01-01

    The effects of the 5-HT₆ receptor antagonists SB-399885 (2.5, 5 and 10 mg/kg) and RO-4368554 (2.5, 5 and 10 mg/kg) and of the 5-HT(2A) receptor antagonist EMD 281014 (2.5, 5 and 10 mg/kg) were studied in rats implanted for chronic sleep procedures. Administration of 10 mg/kg SB-399885, i.p., to rats 2 h after the beginning of the light phase of the light-dark cycle caused a significant increase of wakefulness (W) and a reduction of slow wave sleep (SWS), REM sleep (REMS) and the number of REM periods during 6-h recording sessions. Light sleep was increased after the whole range of doses. The increase of W and reduction of SWS and REMS occurred predominantly during the first 2-h period whereas light sleep was augmented over the first and the second 2-h recording periods. Injection of RO-4368554 (10 mg/kg, i.p.) 2 h after the beginning of the light period significantly increased W and reduced SWS and REMS during the first 2-h recording period. Administration of EMD 281014 (10 mg/kg, i.p.) during the light phase significantly increased SWS and reduced light sleep during 6-h sessions. REMS and the number of REM period were reduced with the entire range of doses. The reduction of REMS and light sleep and the increase of SWS occurred predominantly during the first and the second 2-h of recording, respectively. Injection of SB-399885 (10 mg/kg, i.p.) 2 h after the beginning of the dark period induced a significant reduction of REMS during the first 2-h of recording. In contrast, RO-4368554 did not modify values corresponding to sleep variables during the dark period. Treatment with EMD 281014 (2.5-10 mg/kg, i.p.) during the dark phase significantly increased SWS during the second 2-h period. Our study supports the proposal that blockade of postsynaptic 5-HT₆ receptors with systemic administration of SB-399885 and RO-4368554 increases W and reduces SWS and REMS during the light phase of the sleep-wake cycle. SB-399885 also induces a suppression of REMS during the dark

  13. Calcium Electroporation: Evidence for Differential Effects in Normal and Malignant Cell Lines, Evaluated in a 3D Spheroid Model.

    Science.gov (United States)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha; Gehl, Julie; Rols, Marie-Pierre

    2015-01-01

    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 (pspheroids 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 (pspheroid 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 treating tumors.

  14. Buffering effects of calcium salts in kimchi: lowering acidity, elevating lactic acid bacterial population and dextransucrase activity.

    Science.gov (United States)

    Chae, Seo Eun; Moon, Jin Seok; Jung, Jee Yun; Kim, Ji-Sun; Eom, Hyun-Ju; Kim, So-Young; Yoon, Hyang Sik; Han, Nam Soo

    2009-12-01

    This study investigates the buffering effects of calcium salts in kimchi on total acidity, microbial population, and dextransucrase activity. Calcium chloride or calcium carbonate was added in dongchimi-kimchi, a watery-radish kimchi, and their effects on various biochemical attributes were analyzed. The addition of 0.1% calcium chloride produced a milder decrease in the pH after 24 days of incubation, which allowed the lactic acid bacteria to survive longer than in the control. In particular, the heterofermentative Leuconostoc genus population was 10-fold higher than that in the control. When sucrose and maltose were also added along with the calcium salts, the dextransucrase activity in the kimchi was elevated and a higher concentration of isomaltooligosaccharides was synthesized when compared with the control. Calcium chloride was determined as a better activator compound of dextransucrase than calcium carbonate, probably because of its higher solubility. Therefore, the results of this study confirm the ability of the proposed approach to modulate the kimchi fermentation process and possibly enhance the quality of kimchi based on the addition of dietary calcium salts.

  15. Antagonistic Effects of Cellular Poly(C) Binding Proteins on Vesicular Stomatitis Virus Gene Expression ▿

    Science.gov (United States)

    Dinh, Phat X.; Beura, Lalit K.; Panda, Debasis; Das, Anshuman; Pattnaik, Asit K.

    2011-01-01

    Immunoprecipitation and subsequent mass spectrometry analysis of the cellular proteins from cells expressing the vesicular stomatitis virus (VSV) P protein identified the poly(C) binding protein 2 (PCBP2) as one of the P protein-interacting proteins. To investigate the role of PCBP2 in the viral life cycle, we examined the effects of depletion or overexpression of this protein on VSV growth. Small interfering RNA-mediated silencing of PCBP2 promoted VSV replication. Conversely, overexpression of PCBP2 in transfected cells suppressed VSV growth. Further studies revealed that PCBP2 negatively regulates overall viral mRNA accumulation and subsequent genome replication. Coimmunoprecipitation and immunofluorescence microscopic studies showed that PCBP2 interacts and colocalizes with VSV P protein in virus-infected cells. The P-PCBP2 interaction did not result in reduced levels of protein complex formation with the viral N and L proteins, nor did it induce degradation of the P protein. In addition, PCBP1, another member of the poly(C) binding protein family with homology to PCBP2, was also found to interact with the P protein and inhibit the viral mRNA synthesis at the level of primary transcription without affecting secondary transcription or genome replication. The inhibitory effects of PCBP1 on VSV replication were less pronounced than those of PCBP2. Overall, the results presented here suggest that cellular PCBP2 and PCBP1 antagonize VSV growth by affecting viral gene expression and highlight the importance of these two cellular proteins in restricting virus infections. PMID:21752917

  16. Effect of phase composition of calcium silicate phosphate component on properties of brushite based composite cements

    Energy Technology Data Exchange (ETDEWEB)

    Sopcak, T., E-mail: tsopcak@imr.saske.sk [Institute of Materials Research of SAS, Watsonova 47, 04001 Kosice (Slovakia); Medvecky, L.; Giretova, M.; Stulajterova, R.; Durisin, J. [Institute of Materials Research of SAS, Watsonova 47, 04001 Kosice (Slovakia); Girman, V. [Institute of Physics, Faculty of Science, P. J. Šafárik University, Park Angelinum 9, 04001 Kosice (Slovakia); Faberova, M. [Institute of Materials Research of SAS, Watsonova 47, 04001 Kosice (Slovakia)

    2016-07-15

    The composite cement mixtures were prepared by mixing brushite (B) with, the amorphous hydrated calcium silicate phosphate (CSPH) or annealed calcium silicate phosphate (CSP composed of Si-saturated hydroxyapatite, wollastonite and silica) phases and water as liquid component. The contents of the silicate-phosphate phase in composites were 10.30 and 50 wt%. The significant effect of both the Ca/P ratio and different solubility of calcium silicate phosphate component in starting cement systems on setting time and phase composition of the final composite cements was demonstrated. The compressive strength of the set cements increased with the filler addition and the highest value (~ 48 MPa) exhibited the 50CSP/B cement composite. The final setting times of the composite cements decreased with the CSPH addition from about 25 to 17 min in 50CSHP/B and setting time of CSP/B composites was around 30 min. The higher content of silica in cements caused the precipitation of fine hydroxyapatite particles in the form of nanoneedles or thin plates perpendicularly oriented to sample surface. The analysis of in vitro cement cytotoxicity demonstrated the strong reduction in cytotoxicity of 10CSPH/B composite with time of cultivation (a low cytotoxicity after 9 days of culture) contrary to cements with higher calcium silicate-phosphate content. These results were attributed to the different surface topography of composite substrates and possible stimulation of cell proliferation by the slow continuously release of ions from 10CSPH/B cement. - Highlights: • Ca/P ratio and solubility of calcium silicate-phosphate components affect the self-setting properties of cements. • Strong relationship between the composite in vitro cytotoxicity and surface microtopography was demonstrated. • Plate-like morphology of coarser particles allowed cells to better adhere and proliferate as compared with nanoneedles.

  17. Effects of nanocalcium carbonate on egg production performance and plasma calcium of laying hens.

    Science.gov (United States)

    Ganjigohari, S; Ziaei, N; Ramzani Ghara, A; Tasharrofi, S

    2017-04-27

    This experiment was conducted to evaluate the effects of nanocalcium carbonate (NCC) instead of calcium carbonate (CC) on egg production, egg weight, egg mass, FCR, blood calcium and egg quality characteristics in laying hens. A total of 120 laying hens were used in a 10-weeks trial, from week 23 to 33 of age. Laying hens were randomly assigned to six treatments with four replications, five hens each. The experimental treatments involved replacing 50% of the CC in the diet by decreasing amounts of NCC and were T1 Basal diet (BD) with 8.06% CC; T2 (6.045% of CC as a negative control); T3 (4.03% of CC replaced by 2.015% NCC); T4 (4.03% of CC replaced by 1.01% NCC); T5 (4.03% of CC replaced by 0.252% NCC) and T6 (4.03 of CC replaced with 0.126%NCC).Egg weight was unaffected by dietary treatments (p > .05). However, the egg production percentage and egg mass in T6 were less than that of other treatments (p < .05). The laying hens in the control group had the best average feed conversion ratio (p < .05). Also, the lowest concentration of calcium in hens' blood was recorded for birds fed T6 (p < .05). The best egg shell quality (relative egg shell weight and egg shell weight/surface) was observed in T1 (p < .05).Collectively, our results demonstrated that NCC could replace CC at a lower inclusion level but extreme reduction of calcium concentration in diets (to 1.43% Ca in the T6 group) reduced production performance, egg quality characteristics, Tibia thickness and blood calcium of laying hens. © 2017 Blackwell Verlag GmbH.

  18. Effects of gadopentetate dimeglumine and gadodiamide on serum calcium, magnesium, and creatinine measurements.

    Science.gov (United States)

    Zhang, Hong Lei; Ersoy, Hale; Prince, Martin R

    2006-03-01

    To investigate the in vivo effects of gadodiamide (Gd-DTPA-BMA) and gadopentetate dimeglumine (Gd-DTPA) on the laboratory measurements of serum calcium, magnesium, and creatinine. Medical records from 1993 to 2004 were reviewed to identify inpatients for whom laboratory data were available regarding serum calcium, creatinine, and magnesium levels before and within one day after gadodiamide and gadopentetate dimeglumine enhanced MRI. Patients who underwent both gadolinium (Gd)-enhanced MRI and iodinated contrast-enhanced examinations on separate days within a six-month period were also identified to compare changes in serum creatinine. Serum creatinine did not increase in 2788 cases following gadopentetate dimeglumine and gadodiamide injection. By comparison, serum creatinine increased from 1.21 to 1.28 mg/dL following iodinated contrast, and there were 20 cases (2.6%) of contrast-induced nephrotoxicity (P Gadopentetate dimeglumine did not affect serum calcium or magnesium measurements. Following 1157 gadodiamide-enhanced examinations, measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL (P < 0.0001) and 34 patients had spurious critical hypocalcemia (<6 mg/dL). Of 60 patients with high-dose gadodiamide injection and renal insufficiency, 36.7% (N = 22) had spurious critical hypocalcemia immediately post MRI. In 216 patients with renal insufficiency, the mean serum magnesium level increased slightly from 1.69 to 1.77 mEq/L following gadodiamide injection (P < 0.0001). Gd-based contrast agents are safe for MRI and MR angiography (MRA), and do not induce nephrotoxicity. However, gadodiamide interferes with serum calcium and magnesium measurements-particularly at high doses and/or with renal insufficiency. (c) 2006 Wiley-Liss, Inc.

  19. Effects of Calcium chloride and magnesium sulphate treatments on ...

    African Journals Online (AJOL)

    ... mg/l solutions of CaCl2 and MgSO4 to investigate the effects of the divalent cations Ca2+ and Mg2+ on visually assessed ripening, the quality of pigments, the total lipids content and the water content. Treatments with both salts in the concentration range used retarded the ripening process in bananas and in pineapples.

  20. Effects of physical variables on settling velocities of calcium and ...

    African Journals Online (AJOL)

    Settling velocity is an important parameter used in modeling solid-liquid flow operations and for evaluating tank volumes in water treatment technology. In the present study, series of bench-scale batch-wise precipitation and settling tests were performed to evaluate the effect of some physical variables such as precipitate ...

  1. Inhibitory effect of stevioside on calcium influx to produce antihypertension.

    Science.gov (United States)

    Lee, C N; Wong, K L; Liu, J C; Chen, Y J; Cheng, J T; Chan, P

    2001-12-01

    Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.

  2. The Effects Of Calcium On Dietary Phosphorus Uptake By Hybrid ...

    African Journals Online (AJOL)

    The effect of the dietary increase of P and Ca levels on weight gain and feed conversion ratio (FCR) was also not significant (P > 0.05). This study showed that dietary fortification with Ca and P probably suppressed weight gain and FCR in the hybrid catfish between 28 and 35 days of the experimental period, with ...

  3. 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.

  4. 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......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 transient global cerebral ischemia in gerbils. For in vitro studies, hippocampal slice cultures derived from 7-day-old mice and grown for 14 days, were submersed in oxygen-glucose deprived medium for 30 min and exposed to PNQX for 24 h, starting together with OGD, immediately after OGD, or 2 h after OGD....... For comparison, other cultures were exposed to the NMDA antagonist MK-801 using the same protocol. Both PNQX and MK-801 displayed significant neuroprotective effects in all hippocampal subfields when present during and after OGD. When added just after OGD, only PNQX retained some neuroprotective effect. When...

  5. [Antagonistic effect and mechanism of Rosuvastatin on myocardial apoptosis in rats with acute myocardial infarction].