Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel bloc...Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.展开更多
AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined ...AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.展开更多
The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thick...The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thickness burns. The preventive or therapeutic administration of verapamil exerted little effects on the arterial blood pressure but could effectively protect the myocardial mitochondrial respiratory function after combined radiation-burn injury in rats.The protective effects of verapamil might exercise through the reduction of calcium content in the mitochondria.展开更多
The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repai...The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue.In this study,the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No.10-0 suture.The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks.Compared with the control group（stoma wrapped with gelfoam soaked with physiological saline）,the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo,suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons.These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.展开更多
Dementia is currently the only leading cause of death that is still on the rise,with its overall costs already surpassing those of cancer and heart disease combined,it has developed into a worldwide crisis.In response...Dementia is currently the only leading cause of death that is still on the rise,with its overall costs already surpassing those of cancer and heart disease combined,it has developed into a worldwide crisis.In response to its serious and far-reaching effects,the US government has established the"National Alzheimer's Project Act"(Public Law 111-375).展开更多
The first case of Prinzmetal angina was described in 1959 by Prinzmetal, et al. Since this description, several triggering factors have been associated with vasospastic angina （VA） and included： illicit drugs such ...The first case of Prinzmetal angina was described in 1959 by Prinzmetal, et al. Since this description, several triggering factors have been associated with vasospastic angina （VA） and included： illicit drugs such as cocaine, amphetamine or marijuana, but also bitter-orange, alcohol, butane, chemotherapy drugs, over-the-counter medication and different antibiotics. Smoking is also a major risk factor for developing VA.t21 Thus, except for smoking, many of conventional atherosclerosis risk factors do not appear to be applicable to VA.t21 However, vasospastic angina can also occur without any triggering factor.展开更多
Objective:The majority of the patients with posttraumatic stress disorders(PTSD) embrace augmented urinary flow of Vanillylmandelic Acid(VMA) than normal subjects owing to superior sympathetic doings,which steer to ca...Objective:The majority of the patients with posttraumatic stress disorders(PTSD) embrace augmented urinary flow of Vanillylmandelic Acid(VMA) than normal subjects owing to superior sympathetic doings,which steer to cardiovascular catastrophe.Urinary flow of VMA was evaluated as sympathoadrenal bustle marker in patients with posttraumatic stress disorder.Calcium ion shows a noteworthy dependability in nervousness owing to its special effects on brain synaptosomes.So this study was conducted to explore the effects of Verapamil on sympathoadrenal motion in patients with PTSD.Methods:Placebo controlled clinical tryout was conducted. At first hundred(100) PTSD patients were chosen and enrolled in the study,from department of Psychological Medicine Dow University of Health Sciences,Karachi.Verapamil 120 mg/day was specified in divided doses to group-Ⅰ(n=50)patients and group-Ⅱ(n =50) patients received placebo therapy on a daily basis for nine weeks.Each and every patient was monitored weekly,all the way through extent of study.Results:Underneath the posttraumatic stress disorder,urinary excretion of VMA was greater.Calcium channel blocker verapamil additionally abolished the embellished retort in urinary flow of VMA appreciably in patients with PTSD. Conclusion:Verapamil was experiential to be exceedingly effectual treatment.It reduces VMA levels in urine, and on the whole cardiovascular threat in PTSD patients.展开更多
Aim： To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug＇s potential as a treatment for erectile dysfunction （ED）. Methods： Preparations of the human corpus cav...Aim： To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug＇s potential as a treatment for erectile dysfunction （ED）. Methods： Preparations of the human corpus cavernosum were obtained from recently deceased young men who had had normal erectile function. The isometric tension and detailed curves were recorded when contractions induced by 10 mmol/L phenylephrine were reduced by different doses of verapamil or the vehicle control （sterile water）. The tension of human corpus cavernosum preparations are described as a percentage of their top tension before adding verapamil or the vehicle. ANOVA and least significant difference tests were used for statistical analysis. Results： Doses of 1μmol/L, 10 μmol/L and 100 μmol/L verapamil resulted in relaxation of （35.28 ± 7.96）%, （55.91 ± 6.41）%, （85.68 ± 4.16）% after 30 min, respectively. The vehicle control at the same time point produced relaxation of （-0.06 ± 10.57）% （P 〈 0.05）. Conclusion： Verapamil is significantly effective in relaxing normal human corpus cavernous smooth muscle induced by phenylephrine in vitro and the relaxant effect depends on the concentration of verapamil. （Asian J Androl 2006 Mar; 8： 195-198）展开更多
This article discusses the characteristics of the drugresistant human cervical carcinoma cell line HeLa/MMC and investigates reversal effect of SDZ-PSC833（PSC833） and Verapamil （Ver） upon HeLa/MMC. Relative conten...This article discusses the characteristics of the drugresistant human cervical carcinoma cell line HeLa/MMC and investigates reversal effect of SDZ-PSC833（PSC833） and Verapamil （Ver） upon HeLa/MMC. Relative content of cell DNA detection, H3-TdR incorporation test and drug-resistance have been experimented, meanwhile a tumor transplant model in the nude mice for Hela/MMC has been established. Then the volume of cancer, tumor weight, curve line of growing up in tumor -bearing nude mouse and its morphological variation of carcinoma organism are observed to evaluate the reversal effect of PSC833 and VER. It has been found that： （1） Compared with HeLa cells,subline HeLaJ MMC Cells＇ drug-resistant capability against Mitomycin（MMC） or cisplatin（DDP） is as 5.02 folds or 2 folds as that of the former, respectively. The Hela/MMC cell line has characteristics of multi- drug resistance and stronger multiplication; （2） PSC833 and VER can reverse resistance of HeLa/MMC to Mitomycin in vivo.PSC833 will be a better candidate for reversing multidrug resistant than verapamil in clinic application.展开更多
Objective: To establish a HPLC method using fluorometric detection for quantitatively determinating intracellular accumulation of verapamil (VER). Methods: Chromatography column was packed with spherisorb ODS(250&...Objective: To establish a HPLC method using fluorometric detection for quantitatively determinating intracellular accumulation of verapamil (VER). Methods: Chromatography column was packed with spherisorb ODS(250×4.6 mm,10 μm).The mobile phase consisted of the mixture of methanol:NaAC (0.01 mol/L): diethylamine (65:35:0.25). The detect wavelength was 280/310 nm (Ex/Em). Results: The standard curve showed a good correlation between concentration and peak area within the range of 5-50 ng/ml. RSD was 0.86%, and recovery radio of loading sample, 100%. The detection limit for cell sample was 0.2-148 ng/ml. Intracellular accumulation of VER was observed to decrease from a 13 fold to 5 fold in K562/ADM cells, and from a 3.5 fold to 4.3 fold in K562/VER cells and from a 2.1 fold to 6.5 fold in K562/ADM/VER cells, compared with the relevant control cells. Conclusion: HPLC method was proved to be sensitive and specific for using to quantitatively determine the intracellular accumulation of VER.展开更多
文摘Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.
基金Supported by the Foundation of the National New Drug Research of China, No. 96-901-05-197
文摘AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.
文摘The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thickness burns. The preventive or therapeutic administration of verapamil exerted little effects on the arterial blood pressure but could effectively protect the myocardial mitochondrial respiratory function after combined radiation-burn injury in rats.The protective effects of verapamil might exercise through the reduction of calcium content in the mitochondria.
基金supported by the Natural Science Foundation of Hubei Province of China,No.2011CDB392
文摘The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue.In this study,the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No.10-0 suture.The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks.Compared with the control group（stoma wrapped with gelfoam soaked with physiological saline）,the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo,suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons.These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.
基金supported by the National Institute of Health,No.R01-NS097800(to TI).
文摘Dementia is currently the only leading cause of death that is still on the rise,with its overall costs already surpassing those of cancer and heart disease combined,it has developed into a worldwide crisis.In response to its serious and far-reaching effects,the US government has established the"National Alzheimer's Project Act"(Public Law 111-375).
文摘The first case of Prinzmetal angina was described in 1959 by Prinzmetal, et al. Since this description, several triggering factors have been associated with vasospastic angina （VA） and included： illicit drugs such as cocaine, amphetamine or marijuana, but also bitter-orange, alcohol, butane, chemotherapy drugs, over-the-counter medication and different antibiotics. Smoking is also a major risk factor for developing VA.t21 Thus, except for smoking, many of conventional atherosclerosis risk factors do not appear to be applicable to VA.t21 However, vasospastic angina can also occur without any triggering factor.
文摘Objective:The majority of the patients with posttraumatic stress disorders(PTSD) embrace augmented urinary flow of Vanillylmandelic Acid(VMA) than normal subjects owing to superior sympathetic doings,which steer to cardiovascular catastrophe.Urinary flow of VMA was evaluated as sympathoadrenal bustle marker in patients with posttraumatic stress disorder.Calcium ion shows a noteworthy dependability in nervousness owing to its special effects on brain synaptosomes.So this study was conducted to explore the effects of Verapamil on sympathoadrenal motion in patients with PTSD.Methods:Placebo controlled clinical tryout was conducted. At first hundred(100) PTSD patients were chosen and enrolled in the study,from department of Psychological Medicine Dow University of Health Sciences,Karachi.Verapamil 120 mg/day was specified in divided doses to group-Ⅰ(n=50)patients and group-Ⅱ(n =50) patients received placebo therapy on a daily basis for nine weeks.Each and every patient was monitored weekly,all the way through extent of study.Results:Underneath the posttraumatic stress disorder,urinary excretion of VMA was greater.Calcium channel blocker verapamil additionally abolished the embellished retort in urinary flow of VMA appreciably in patients with PTSD. Conclusion:Verapamil was experiential to be exceedingly effectual treatment.It reduces VMA levels in urine, and on the whole cardiovascular threat in PTSD patients.
文摘Aim： To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug＇s potential as a treatment for erectile dysfunction （ED）. Methods： Preparations of the human corpus cavernosum were obtained from recently deceased young men who had had normal erectile function. The isometric tension and detailed curves were recorded when contractions induced by 10 mmol/L phenylephrine were reduced by different doses of verapamil or the vehicle control （sterile water）. The tension of human corpus cavernosum preparations are described as a percentage of their top tension before adding verapamil or the vehicle. ANOVA and least significant difference tests were used for statistical analysis. Results： Doses of 1μmol/L, 10 μmol/L and 100 μmol/L verapamil resulted in relaxation of （35.28 ± 7.96）%, （55.91 ± 6.41）%, （85.68 ± 4.16）% after 30 min, respectively. The vehicle control at the same time point produced relaxation of （-0.06 ± 10.57）% （P 〈 0.05）. Conclusion： Verapamil is significantly effective in relaxing normal human corpus cavernous smooth muscle induced by phenylephrine in vitro and the relaxant effect depends on the concentration of verapamil. （Asian J Androl 2006 Mar; 8： 195-198）
基金Supported by the Key Scientific and Technical Research Project of Hubei Provicial Department of Education (EK980038)
文摘This article discusses the characteristics of the drugresistant human cervical carcinoma cell line HeLa/MMC and investigates reversal effect of SDZ-PSC833（PSC833） and Verapamil （Ver） upon HeLa/MMC. Relative content of cell DNA detection, H3-TdR incorporation test and drug-resistance have been experimented, meanwhile a tumor transplant model in the nude mice for Hela/MMC has been established. Then the volume of cancer, tumor weight, curve line of growing up in tumor -bearing nude mouse and its morphological variation of carcinoma organism are observed to evaluate the reversal effect of PSC833 and VER. It has been found that： （1） Compared with HeLa cells,subline HeLaJ MMC Cells＇ drug-resistant capability against Mitomycin（MMC） or cisplatin（DDP） is as 5.02 folds or 2 folds as that of the former, respectively. The Hela/MMC cell line has characteristics of multi- drug resistance and stronger multiplication; （2） PSC833 and VER can reverse resistance of HeLa/MMC to Mitomycin in vivo.PSC833 will be a better candidate for reversing multidrug resistant than verapamil in clinic application.
文摘Objective: To establish a HPLC method using fluorometric detection for quantitatively determinating intracellular accumulation of verapamil (VER). Methods: Chromatography column was packed with spherisorb ODS(250×4.6 mm,10 μm).The mobile phase consisted of the mixture of methanol:NaAC (0.01 mol/L): diethylamine (65:35:0.25). The detect wavelength was 280/310 nm (Ex/Em). Results: The standard curve showed a good correlation between concentration and peak area within the range of 5-50 ng/ml. RSD was 0.86%, and recovery radio of loading sample, 100%. The detection limit for cell sample was 0.2-148 ng/ml. Intracellular accumulation of VER was observed to decrease from a 13 fold to 5 fold in K562/ADM cells, and from a 3.5 fold to 4.3 fold in K562/VER cells and from a 2.1 fold to 6.5 fold in K562/ADM/VER cells, compared with the relevant control cells. Conclusion: HPLC method was proved to be sensitive and specific for using to quantitatively determine the intracellular accumulation of VER.
