Research of the Curative Effect about New Compound Dressing in Promoting Epithelial Repaired of Ⅱ ° Burned Wound in Rats / 医学研究杂志

Objective To develop a new compound dressing which can both anti-inflammatory and promote skin quickly epithelial repairing,and then study the curative effect.Methods First,the wound injury model was established.The samples were randomly divided into normal,injury and treatment group which were treated with dressing after injury.Next,the wound skin tissues were taken in injured after 1days,3days,7days and 14days.Then,each area of the wound was measured and the wound healing rate were calculated.Total Ca2 + concentration and the difference of active oxygen in skin tissue between each groups were compared.The secretion of TNF-α,IL -1 and IL-6 were detected by RIA method as follow.Results The new compound dressing can effectively shorten healing time,which is 25.39 ± 3.12days (the treatment group) comparing with 29.46 ± 4.38days (the injury group) (P ＜ 0.05).And it promotes the formation of skin island in 14days and increase the healing rate(P ＜ 0.05).Besides,the new compound dressing can effectively reduce the total Ca2+ concentration,lower the level of the inflammation factors and the ROS after injury,the results of each period of two groups were significant difference(P ＜0.05).Conclusion New compound dressings can effectively promote skin epithelial repairing,block intra cellular calcium ion channels,reduce the release of inflammation factors and inhibit the reaction of oxidative stress,which provide a new treatment for wound repair.

Calcium antagonists protect cardiac microvascular endothelialcells against hypoxia/reoxygenation injury through iPLA2 / 中国药理学通报

Aim To investigate the effects of classic calcium antagonists verapamil(Ver),nifedipine(Nif),diltiazem(Dil)and the novel calcium antagonist N-n-butyl haloperidol iodide(F2)which was synthesized by our lab by regulating Ca2+-independent phospholipase A2(iPLA2)on hypoxia/reoxygenation(H/R)injury of cardiac microvascular endothelial cells(CMECs)and the mechanisms.Methods The CMECs were isolated from SD neonatal rats.The H/R model was established,then cells were treated with different concentrations of calcium antagonists and F2.The content of LDH in the cell supernatant was measured by colorimetric method.The levels of IL-6 and AA in cell supernatant were measured by ELISA;and late-stage apoptosis was measured by TUNEL.The mRNA and protein expression levels of iPLA2 in CMECs were examined by real time-PCR and Western blot analysis.Results Calcium antagonists except Dil decreased the generation of LDH,IL-6 and AA in a dose-dependent manner(P<0.05),and reduced the apoptosis(P<0.05).F2 and Ver decreased the mRNA and protein expression of iPLA2 in a dose-dependent manner,while there were no such effects for Nif and Dil.Conclusions Calcium antagonists except Dil have protective effects against H/R injury.F2 and Ver protect CMECs against H/R injury partly through iPLA2.

Relationship between calcium overload and myocardial ischemia reperfusion injury and intervention strategy of Chinese herbal medicine / 中国中药杂志

The recent report from National Cardiovascular Center shows that cardiovascular diseases account for more than 40% of disease deaths among residents, so it has become the first cause of death among the residents in our country, and the mortality of coronary heart disease is increasing year by year. Revascularization can quickly open the clogged blood vessels and restore coronary blood supply, so it is an important approach for the treatment of coronary heart disease. However, the revascularization can not terminate the pathological development of coronary heart disease because it is just a local treatment method. In addition, a series of reperfusion injuries after revascularization would seriously restrict its treatment effect for coronary heart disease. Myocardial ischemia reperfusion injury is a complex pathological process, which is closely related to oxygen free radicals, calcium overload and energy metabolism disorder. The calcium overload can be seen during reperfusion in the myocardial cells, and it can cause further damages to the myocardial cells through various mechanisms. Calcium overload is a common pathway of myocardial necrosis and apoptosis, so prevention and treatment of calcium overload is an important method to prevent ischemia reperfusion. The commonly used calcium channel blockers for preventing calcium overload has made great progress, all of which can act on L-type calcium channel of vascular smooth muscle to inhibit calcium overload. However, their clinical application was restrained to a certain extent due to the single target and great side effects. Traditional Chinese medicine (TCM) is a great treasure, and many drugs in TCM have similar effects with calcium antagonists, so the development and application of such drugs would be an important task for contemporary TCM doctors to make up for the deficiency of Western medicine.

Effects of Four Dihydropyridine Calcium Antagonists on CYP3 A4 Enzyme Activity Induced By Dexametha-sone in Female Rats / 中国药师

Objective:To study the inhibition effects of four dihydropyridine calcium antagonists felodipine, nicardipine, lercani-dipine and nifedipine on CYP3A4 enzyme to provide the theoretical basis for the understanding of the drug interactions between dihydro-pyridine calcium antagonists and other drugs. Methods:Using the probe drugs method, the SD female rats induced by 80 mg·kg-1 · d-1 dexamethasone for three days were divided into the negative control group, positive control group, four DHPs groups with six ones in each. Dapsone was used as the probe substrate, and the concentration was determined by HPLC. Data analysis software WinNonLin was used in the pharmacokinetic model fitting process and the paired t-test was used in the statistical analysis. Results: AUC0-24 and CL/F of dapsone in the negative control group showed statistically significant differences when compared with those in the four DHPs groups and the positive group (Pnicardipine > lercanidipine > felodipine, the difference was not statistically significant (P>0. 05). Cmax of dapsone in the DHPs groups and the positive group had no statistically significant difference when compared with that in the negative control group ( P>0. 05). Conclusion:Although there are different inhibition effects on CYP3A4 among the four DHPs, the differences are not significant in vivo, and there is no influence on the combination drugs which is not mainly metabolized by CYP3A4.

Uso de flunarizina en un caso con síndrome de Landau-Kleffner / Use of flunarizine in a case of Landau-Kleffner syndrome

Introducción. El síndrome de Landau-Kleffner se caracteriza por afasia adquirida y anormalidades electroencefalográficas durante la vigilia y el sueño. El tratamiento con anticonvulsivos controla las crisis convulsivas pero en los problemas de lenguaje y comportamiento su eficacia es menor. Algunos reportes señalan mejoría de lenguaje con el uso de corticoesteroides en etapas tempranas y a dosis altas. Otra opción terapéutica es el uso de calcioantagonistas. Caso clínico. Paciente de 5 años de edad con evolución normal hasta los 2 años hasta que los padres observaron la pérdida espontánea del lenguaje previamente adquirido. En la evaluación neurológica se encontraron abundantes ecolalias e indiferencia a estímulos externos. El electroencefalograma mostró brotes intermitentes de ondas agudas y complejos punta-onda lenta de 3-4 Hz generalizados durante el sueño. Se inició tratamiento con prednisona por un mes y ácido valproico. Se continuó con el ácido valproico y después de 4 meses se añadió flunarizina, con lo que se observó mejoría en el lenguaje. Conclusiones. Este caso presenta los hallazgos clínicos y electroencefalográficos del síndrome; se observó que la mejor respuesta al tratamiento se obtuvo al agregar flunarizina. Esta evidencia contribuye a apoyar su uso y fundamenta la realización posterior de estudios controlados para concluir certeramente sobre su utilidad en el padecimiento.

Background. Landau-Kleffner syndrome is characterized by acquired aphasia and electroencephalographic abnormalities during wake-fulness and sleep. These abnormalities can be solved with anticonvulsive medications, but speech and behavioral problems cannot be treated using this therapy. Instead, there are reports that indicate that treatment with high-dose corticosteroids during early stages of the disease improves the speech difficulties. Use of calcium antagonists has also been proposed as possible treatment. Case report. We report the case of a 5-year-old patient with normal development until the age of 2 years. At that time, the parents observed loss of spontaneous acquired speech. During neurological evaluation, the child showed abundant echolalia and indifference to external stimuli. Electroencephalogram showed sharp waves and generalized slow spike-wave complexes of 3-4 Hz during sleep. We began treatment with prednisone and valproic acid for 1 month; flunarizine was added. After 4 months of treatment, the patient showed speech improvement. Conclusions. Our case has the characteristic clinical and electroencephalographic findings of Landau-Kleffner syndrome. We observed significant symptom improvement when flunarizine was added to the treatment. This evidence offers support for the use of a calcium antagonist as possible therapy, which may help setting the way for future controlled studies in order to finally establish its utility with this illness.

Total Asymmetric Synthesis of 3'R,4'R-Disubstituted Angular Dihydropyranocoumarins / 中国药科大学学报

AIM:To obtain new typical compounds with dual mechanism,antagonizing Ca2+and inhibiting acetylcholinesterase,on Alzheimer's disease.METHODS:Resorcinol was chosen as primitive substrate,and AD-mix-β as asymmetrically dihydroxylated reagent;all products were screened against acetylcholinesterase in vitro.RESULTS:cis-3′R,4′R-disubstituted angular dihydropyranocoumarins were synthesized enantioselectively,however,its inhibitory activity on acetylcholinesterase is distinctively lower than that of cis-3′R,4′R-disubstituted linear dihydropyranocoumarins.

INHIBITION OF TRYPANOSOMA CRUZI GROWTH IN MAMMALIAN CELLS BY NIMODIPINE, WITH LOW CYTOTOXICITY TO HOST CELLS

An in vitro infection system of <I>Trypanosoma cruzi</I> and HeLa cells was used to measure the anti-<I>T. cruzi</I> activities of various calcium antagonists classified into dihydropyridines, diphenylalkylamines, and benzothiazepines and of allopurinol and benznidazole as medium and highly effective reference compounds, respectively. Six dihydropyridines (10 μM each), i. e. nifedipine, nicardipine, nimodipine, nisoldipine, nitrendipine, and amlodipine, decreased the rates of infection of HeLa cells from 11.7% (control) to 5.8, 0.9, 1.2, 3.6, 5.9, and 1.7%, respectively. Nicardipine and amlodipine were highly toxic to HeLa cells, causing detachment of cells from coverslips. Nimodipine was thus the most effective inhibitor tested against <I>T. cruzi</I> infection in HeLa cells. Verapamil and gallopamil (diphenylalkylamines), diltiazem and midazolam (benzothiazepines), and allopurinol (positive control) were less effective than nimodipine. IC<SUB>50</SUB> values, the concentrations of compounds that elicited a 50% reduction in the infection rates of HeLa cells, were 2.5, 2.6, 1.3, 2.1, and 1.7 μM for nicardipine, nimodipine, amlodipine, verapamil, and benznidazole, respectively, while the values for nifedipine, diltiazem, and allopurinol were much higher. Nicardipine, amlodipine, and verapamil again showed significant cytotoxicities to HeLa cells. When Swiss 3T3 fibroblasts replaced HeLa cells, nimodipine markedly lowered the host-cell-infection rate, with an IC<SUB>50</SUB> value of 8.3 nM. Thus, nimodipine is expected to be a highly effective anti-<I>T. cruzi</I> lead compound, with low cytotoxicity to mammalian cells. Structural formulas of nimodipine and nicardipine in relation to their low and high cytotoxicities, respectively, against HeLa cells are discussed.

Pharmacokinetics of dipfluzine hydrochloride in Beagle dogs after single intravenous dose / 中国药理学通报

Aim To investigate the pharmacokinetics of dipfluzine hydrochloride,a novel piperazines calcium antagonist.Methods Eighteen Beagle dogs were randomly divided into three groups,which were administered with dipfluzine hydrochloride at iv single dose of 1.5,3.0 and 6.0 mg?kg-1,respectively.The blood was collected at different time.A RP-HPLC method was developed to determine the concentration of dipfluzine hydrochloride in plasma.The pharmacokinetic parameters were calculated by 3P97 software.Results The specificity,lowest limit of detection and quantification,extraction recoveries,the precision of intra-and inter-day and stability were qualified to the pharmacokinetic study.The concentration-time courses of dipfluzine hydrochloride were best fitted to a two-compartment open model at three doses.The main pharmacokinetic parameters at three doses were 24.7,24.2 and 29.6 h for T12?,0.44,1.12 and 2.86 g?min?L-1 for AUC,1.30,1.22 and 1.28 L?kg-1 for Vc,and 3.4?10-3,2.7?10-3 and 2.1?10-3 L?kg-1?min-1 for CL,respectively.Conclusions The developed RP-HPLC method for determination of dipfluzine hydrochloride in plasma can satisfy the requirement of pharmacokinetic study after iv dipfluzine hydrochloride.Analysis of plasma concentration-time curves indicates a biphasic decrease.There was a linear relationship between AUC and dosage.

Treatment of Problem Scars through Intralesional Calcium Antagonist Injection

Scars can be problematic if they accompany the skin rash, tenderness, pruritus, limited joint motion, or various cosmetic complaints. Burn scar contractures, hypertrophic scars, irregular elevated scars and keloids are defined as problem scars. Many treatment modalities for control of excessive scars were introduced, but the results was often difficult to predict and some had high recurrence rates. Among current therapies for scar management, calcium antagonists were reported to induce the increasing activity of collagenase and promote the phenotypic changes in fibroblast. As a result, softening of the scars and lightening of color were established by intralesional calcium antagonist injection. From March 2001 to February 2002, we had treated 25 patients who had problem scars. Our treatment modality was performed that the calcium antagonist, as verapamil, was injected intralesionally with a total of 4 times at intervals of 3 weeks. Through the mean 6.2 months of follow-up period, there were 19 patients who had significant improvement in volume, texture, and color of scars. No complications and recurrence occurred with calcium antagonist injections. Intralesional injection of calcium antagonists has been an effective method for the treatment of problem scars, especially in case of worrying side effects or contraindicated situations in steroid therapy.

Mechanism of intracellular calcium regulation and related clinical application / 中国药理学通报

Calcium ion is involved in many processes of cellular living activities. It is critically important for maintaining normal functions of human body. The review will discuss intracellular calcium regulation, distribution changes of calcium in ischemic cerebravascular and cardiovascular diseases, and intracellular intervention of calcium by specific drugs.

Improvement in endothelial function by calcium antagonist and vitamin C in essential hypertension / 대한내과학회지

BACKGROUND: The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was 1) to evaluate the endothelial function in hypertensive patients 2) to investigate whether vitamin C administration has any benefit on the endothelial function and 3) to determine whether treatment with calcium antagonist improves endothelial dysfunction in hypertensive patients. METHODS: The endothelial function was estimated using venous occlusion plethysmography (VOP) in 8 hypertensive patients and 8 healthy volunteers. The patients in the hypertension group were treated with amlodipine, then examined again. The change of forearm blood flow (FBF) was measured with acetylcholine infusion through brachial artery and also with intra-arterial vitamin C. RESULTS: Forearm blood flow response to acetylcholine was significantly enhanced with intra-arterial infusion of vitamin C in hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA, an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After treatment with amlodipine for 2 months in hypertensive group, endothelium- dependent vasorelaxation to acetylcholine was significantly improved compared to pretreatment, and vitamin C did not affect the improved endothelial function by amlodipine treatment. CONCLUSION: Vitamin C (acutely) and amlodipine (chronically) improved endothelial function in hypertensive patients. These results suggest that increased oxidative stress, at least in part, may be involved in the decreased endothelial function in hypertension.

Analysis of Calcium Antagonists Used in Some Hospitals of Guangdong Province from 2002 to 2004 / 中国药房

OBJECTIVE:To evaluate the status quo and the tendency of calcium antagonists used in Guangdong Province.METHODS:The consumption sum,DDDs and the average daily expenses of calcium antagonists in Guangdong Province from2002to2004were analyzed statistically.RESULTS:The consumption sum of calcium antagonists from2002to2004increased year by year,with amlodipine leading the list of consumption sum and nifedipine leading the list of DDDs.CONCLUSIONS:Dihydropyridine calcium antagonists dominate Guangdong market.

Effects of calcium channel blockers on porcine cardiac and coronary arterial function in ischemia-reperfusion

This study was designed to investigate effects of calcium antagonists on endothelial and neuronal dysfunction of right coronary artery (RCA) induced by ischemia- reperfusion in anesthetized, open-chest pigs. After reperfusion, pigs were sacrificed and the RCA was rapidly dissected for in vitro experiments. Experimental groups were divided into 4 groups: control (C-RCA), ischemia-reperfusion only (I-RCA), verapamil infusion (VI-RCA) and nifedipine infusion (NI-RCA) group, respectively. The ischemia did not affect hemodynamics, mean arterial pressure, heart rate, LVdP/dtmax, and decreased RCA flow. Arterial pressure and heart rate during ischemia-reperfusion were decreased in VI-RCA and NI-RCA, and RCA flow during reperfusion was increased in NI-RCA. 5-Hydroxytryptamine (5-HT) produced concentration-dependent contractions in C-RCA. The 5-HT-induced contractions were potentiated in I-RCA and VI-RCA, but not in NI-RCA. Endothelium-dependent relaxation by calcium ionophore A23187 was inhibited in I-RCA and VI-RCA, and recovered in NI-RCA. Cyclic GMP contents were decreased in I-RCA group alone. Electrical field stimulation in C-RCA produced transient and frequency-dependent contractions and at 50 Hz caused biphasic contractions. The transient contractions were not affected by pretreatment with phentolamine and atropine, but the biphasic contraction was altered by the pretreatment. Both contractions were inhibited in I-RCA, and were partially recovered in VI-RCA and NI-RCA. Ischemia-reperfusion of RCA in pigs causes endothelial and neuronal dysfunctions, and calcium antagonists partially prevent both.

Substances interfering with phosphatidyl inositol signalling pathway affect ultradian rhythm of Desmodium motorium.

The ultradian rhythm of the lateral leaflets of Desmodium motorium (Houtt.) Merril. was recorded with a picture analysis method using a video camera and a computer. The periods are in the minute range and depend strongly on temperature. The phosphatidyl inositol signal chain might be involved in the ultradian rhythm of the lateral leaflet movement of Desmodium motorium: Myoinositol shortens the period length and reduces the known period lengthening effect of lithium ions. Neomycin, which inhibits the hydrolysis of phosphatidylinositol-4, 5-biphosphate to inositol-4-phosphate and diacylglycerin, lengthens the period of the rhythm at low concentrations (0·2 mM). Higher concentrations shorten the period, perhaps by activating G protein. Mastoparan, which activates G protein, shortens period likewise. The G protein agonists fluorid ion and ethanol are toxic for the lateral leaflets and could therefore not be used to test the involvement of G protein. The intracellular Ca2+ antagonist 3, 4, 5-trinietlioxybeiizoic acid 8-(diethylamino)octylester lengthens the period of the rhythm. This indicates, that release of Ca2 + from intracellular stores is important for the lateral leaflet movement rhythm.

Intrathecal Endothelin-1 Reduced the MAC of Isoflurane in the Rat / 대한마취과학회지

BACKGROUND: Recent evidences suggest that anesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli. Intrathecal endothelin-1 (ET-1) is known to have antinociceptive effect. The purpose of this experiment was to determine whether intrathecal ET-1 may influence the minimum alveolar concentration (MAC) of isoflurane in rats and access the role of the spinal cord as the sites of anesthetic action in blocking somatic responsiveness. METHODS: In Sprague-Dawley rats fitted with an indwelling intrathecal catheter, we determined the MAC of isoflurane using a tail-clamp technique as a painful stimulus, combined with end-tidal anesthetic sampling. In experiment 1, the control MAC was determined and changes of control MAC were observed after intrathecal ET-1 (4x10-2 nmol, 4x10-3 nmol) administration. In experiment 2, we observed the effects of L or N type Ca++ channel blocker such as verapamil (50 g) or W-conotoxin (0.5 g) on the MAC after measurement of the control MAC. In experiment 3, after measurement of the control MAC, ET-1 (10-2 nmol) was administered intrathecally and the MAC was determined again. Next, intrathecal verapamil (50 g) or W-conotoxin (0.5 g) was injected. After that, the MAC was determined again. RESULTS: In experiment 1, ET-1 decreased the MAC of isoflurane and its effect was sustained over 2 hours. In experiment 2, the MAC, determined following administration of verapamil or W-conotoxin, was not different from that of the control. In experiment 3, the MAC was decreased after ET-1 administration and then increased following injection of verapamil or W-conotoxin. CONCLUSIONS: These results suggested that ET-1, in relation to calcium, might play an important role in determining the MAC of isoflurane in the spinal cord.

The Effect of Topical Nilvadipine on Cerebral Pial Vessels in Rabbit

The effects of mock CSF, nilvadipine solution of various concentrations and PEG 400 solution on regional cerebral pial vessels in rabbits were studied by topical microapplication to the perivascular evironment through the bilateral cranial windows in a randomized fashion. Physiological parameters(PaO2, PaCO2, blood pH, and systolic blood pressure) were not significantly changed during all experiments. The pial vascular diameter was directly determined with the micrometer eyepiece under the operating microscope. The results were the followings: 1) Topical applications with mock cerebrospinal fluid(Group I) and PEG 400(Group II) on cerebral pial vessels did not significantly change pial vascular diameter in comparison with the resting state(p>0.05). 2) Application of nilvadipine solution of 1x10(-8)M did not show significant dilatation, and solutions over the range of 1x10(-7) to 1x10(-2)M resulted in significant dilatation of the cerebral pial arteries in a dose-dependent manner. The small arterial segments showed more dilatation than large arterial segments when topical nilvadipine solution were applied, however, the difference was not significant(p>0.05). 3) In venous segments, topical application of the nilvadipine solution induced no significant pial vein dilatation compared with the resting state(p>0.05), except when 10 minutes after the topical application of 1x10(-2)M nilvadipine solution(p<0.05). It may be suggested that topical application of nilvadipine solution induce the dilatation of pial arteries with dose-dependent manner. Nilvadipine might be used for treatment and prevention of cerebral vasospasm and ischemia.

Calcium Antagonist in the Management of Aneurysmal Subarachnoid Hemorrhage Patient

To evaluate the effectiveness and to find out which grade(clinical and computed tomography) of subarachnoid hemorrhage(SAH) patients are most effected with the medication of the calcium antagonist, we did this study. We selected 339 cases(study cases) among a total of 603 cases of SAH who were admitted to our hospital from Sept. 1982 to Aprial 1991. The criteria of study cases are patients who were admitted and who had a brain computed tomography(CT) taken within 3 days after the SAH and who had a clinical grade(Hung & Hess) on admission between I-IV. We divided study cases into 3 groups. Group I:surgery was done more than 7 days after the SAH and together with non-surgical patients, no medication was used(N=126). Group II:surgery was done more than 7 days after teh SAH and together with non-surgical patients medication of the calcium antagonist was given orally(N=120). Group III:surgery was done more than 7 days after the SAH and together with non-surgical patients, medication of nimodipine intravenously was given, and also patients, medication of nimodipine intravenously was given, and also patients who received surgery did within 3 days after the SAH were given intravenous injection and cisternal irrigation of nimodipine(N=93). We compared the overall management outcome and the incidence of delayed ischemic dificit(DID) and unfavorable outcome due to DID in each group. We also analyzed the causes of unfavorable outcome according to the clinical grade on admission and the amount of blood in the cistern seen on the brain CT in each group. The results of this study showed that overall management outcome was improved by using the calcium antagonist. The calcium antagonist reduced the incidence of DID as well as the unfavorable outcome related to DID. In clinical grade III patients on admission, the unfavorable outcome due to DID was significantly lower in group II and III than in I(group I vs. II:p<0.05, group I vs. III:P<0.01). In cases with a large amount of blood in the cistern seen on the brain CT, the unfavorable outcome was significantly lower in groups II and III than in I(group I vs. II:p<0.01, group I vs. III:p<0.05). We conclude that the overall management outcome of aneurismal SAH patients may be improved by using a calcium antagonist and the effect of the calcium antagonist is prominent in clinical grade III patients on admission and patients with a large amounts of blood in the cistern seen on the brain CT.

The effect of calcium antagonist on Bcl-2 and Bax genes expression after cerebral ischemia in rats / 临床神经病学杂志

Objective To explore Bcl-2 and Bax gene expression in hippocampus region after cerebral ischemia in rats and the modulation of expression by Nimodipine.Methods The cerebral ischemic model of rat was made by occluding left middle cerebral artery according to Nagasawy and Zea Longa improvement method. The rats in one group were pre-treated with Nimodipine. The expression of Bcl-2 and Bax mRNA were measured by RT-PCR method.Results Both Bcl-2 and Bax mRNA were induced in the hippocampus regions after middle cerebral artery occlusion. The Bcl-2 mRNA level was continuously high. However,the level of Bax mRNA increased gradually at first,reached a peak at 24 h,then decreased slowly.For the rats pretreated with Nimodipine Bcl-2 mRNA was up-regulated and Bax mRNA was down-regulated in the hippocampus at 6 and 24 h after ischemia.Conclusion Calcium antagonist can regulate Bcl-2 and Bax genes expression in the hippocampus region after cerebral ischemia.This study indicates that pharmacological modulation of Bcl-2 family member expression may become a new strategy to interfere with neuronal damage.

A Clinical Study of Antihypertensive Effects of Amlodipine(Norvasc(R)) in Essential Hypertension

BACKGROUND: To evaluate the safety and the efficacy of amlodipine, a dihydropyridine calcium antagonist, monotherapy in the treatment of moderate essential hypertension. METHOD: Amlodipine 5mg once a day was administered as a starting dose in 30 patients with essential hypertension in the morning and a one step upward titration was performed (amlodipine 10 mg once a day) was done at the end of 4weeks treatment. Final evaluation was done at 12weeks with laboratory test and echocardiogram. RESULT: Within 4weeks treatment with dose of 5mg amlodipine once a day, the systolic blood pressure (SBP) was decreased(184.5+/-23.3/150.5+/-16.0mmHg,p<0.000), and the diastolic blood pressure(DBP) was also decreased significantly (109.9+/-04.6/92.3+/-11.5mmHg, P<0.001). After 12 weeks of treatment with a mean dosage of 6.6mg once a day, SBP and DBP was maintained comparing with basal level (147.0+/-15.8/88.1+/-0.9mmHg, respectively). The efficacy of amlodipine treatment was noted an excellent in 16 patients(53.3%), good in 4 patient(13.3%), fair in 4 patients(13.3%), and failed in 2 patients(6.7%). There was no significant change in heart rate before and after amlodipine treatment. (80.0+/-2.3/80.9+/-10.4 beats/minute n.s). Amlodipine had not significant effects on laboratory findings such as serum creatinine, BUN, ALT/AST, hemoglobin, leukocyte count,platelet and lipid profiles. There was facial flushing 2 patients, but no need to discontinue administration of amlodipine and all patients completed for 12weeks therapy. CONCLUSION: It is concluded that amlodipine is an effective antihypertensive agent, as monotherapy once a day in patients with moderate essential hypertension.

Eficácia e tolerabilidade de um novo bloqueador dos canais de cálcio (Nitrendipina) no tratamento da hipertensäo arterial / Efficacy and tolerability of a new calcium antagonist (nitrendipine) in the treatment of hypertension

Objetivo: Avaliar a eficácia e a tolerabilidade da monoterapia por nitrendipina, 20 mg ao dia, em portadores de hipertensão arterial sistêmica leve ou moderada. Material e Métodos: Vinte pacientes submetidos durante seis semanas a estudo aberto comparado (droga x placebo), avaliados através de pressão arterial em posição ortostática, supina e após manobra de hand-grip a cada duas semanas e exames laboratoriais no início e final do estudo. Resultados: As pressões médias sistólica e diastólica apresentaram queda significativa no grupo tratado, nas posições supina (161 mmHg ± 11 para 138 mmHg ± 5 e 105 mmHg ± 5 para 81 mmHg ± 7 -p < 0,05), ortostática (153 mmHg ± 13 para 132 mmHg ± 13 e 104 mmHg ± 5 para 81 mmHg ± 7 -p < 0,05) e após hand-grip (170 mmHg ± 21 para 148 mmHg ± 22 e 108 mmHg ± 5 para 85 mmHg ± 7 -p < 0,05). O grupo placebo não apresentou variações significativas das pressões médias sitólica e diastólica em quaisquer das condições: supina (168 mmHg ± 8 para 168 mmHg 18 e 107 mmHg ± 5 para 107 mmHg ± 3 mmHg), ortostática (167 mmHg ± 9 para 163 mmHg ± 14 e 107 mmHg ± 5 para 107 mmHg ± 4) e após hand-grip (178 mmHg ± 17 para 173 mmHg ± 16 e 107 mmHg ± 4 para 108 mmHg ± 6. Não houve modificação significativa das médias da freqüência cardíaca em ambos os grupos após o tratamento. A elevação da freqüência cardíaca verificada após manobra de hand-grip também não se modificou. Dos eventuais efeitos adversos, observavam-se cefaléia, palpitação e tontura, que estiveram presentes em ambos os grupos (placebo e nitrendipina). Os exames eletrocardiográfico, radiológico e laboratorial não se alteraram ao longo do estudo...

Purpose: Assess the efficacy and tolerability of nitrendipine, 20 mg/day, in mild to moderate essential hypertension (diastolic blood pressure 95 to 114 mmHg). Material e Methods: Twenty patients in an open comparative trial (drug x placebo) during six weeks. Blood pressure and heart rate were measured in ortostatic and supine position and after hand-grip manewre every two weeks. Results: Systolic and diastolic blood pressure fell significatively in the treated group by the end of the study-supine (161 mmHg ± 11 to 138 mmHg ± 13 and 105 ± 5 to 81 mmHg ± 7 p < 0,05) and ortostatic position (153 mmHg ± 13 to 132 mmHg ± 13 and 104 mmHg ± 15 to 81 mmHg ± 7, p < 0,05) and after hand grip maneuver (170 mmHg ± 21 to 148 mmHg ± 22 and 108 mmHg ± 5 to 85 mmHg ± 7 p< 0,051. Significant modifications were not observed in systolic and diastolic blood pressure in placebo group under the following conditions: supine (168 mmHg ± 8 to 168 mmHg ± 17 and 107 mmHg ± 5 to 107 mmHg ± 3) and ortostatic positions (167 mmHg ± 9 to 163 mmHg ± 14 and 107 mmHg ± 5 to 107 mmHg ± 4) and after hand grip maneuore (178 mmHg ± 17 to 173 mmHg ± 16 and 107 mmHg ± 4 to 108 mmHg ± 6). Significant changes in heart rate did not occur in both groups after treatment. Heart rate elevation observed after hand grip maneuvre did not change. Adverse effects like headache, palpitation and dizziness occurred in both groups. Eletrocardiogram, x-ray and blood chemistries were not modified during the trial...