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
Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that ...Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer＇s disease. Calcium channel blockers are effective therapeutics for treating Alzheimer＇s disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer＇s disease theraov.展开更多
Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibi...Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.展开更多
The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast...The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast cell activation.We studied the effect of the calcium ionophore A 23187 and calcium channelblockers,nifedipine and verapamil, in triggering the activation of rat peritoneal mast cells.At suitableconcentration nifedipine and verapamil have had the inhibition effect in the IgE-dependent roaction.展开更多
\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) ...\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) had no effect on the resting [Ca2+]i, but had inhibitory effects on [Ca2+]i elevation induced by high K+, 5HT, ATP, Ang II and NE in the presence of extracellular Ca2+. High concentration of Tet also inhibited Pheinduced [Ca2+]i elevation in absence of extracellular Ca2+. Tet (1～100 μmol·L-1) inhibited KCl (60 mmol·L-1) induced [Ca2+]i elevation in dosedependent manner, the IC50 value was 9.2 (95% confidence limits: 5.7～14.9) mmol·L-1. The results suggested that Tet had blocking effects on both VOC and ROC in bovine aortic SMC. It appears that the mechanisms of blocking effect of Tet on ROC might be primarily due to its Ca2+ entry blocking effects.展开更多
Calcium ions （Ca2＋） act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roo...Calcium ions （Ca2＋） act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roots is caused by the transport of auxin from the irradiated side to the shaded side of the roots. To clarify the role of calcium signaling in the modulation of rice root negative phototropism, as well as the relationship between polar auxin transport and calcium signaling, calcium signaling reagents were used to treat rice seminal roots which were cultivated in hydroculture and unilaterally illuminated at an intensity of 100-200 pmol/（m2.s） for 24 h. Negative phototropism curvature and growth rate of rice roots were both promoted by exogenous CaCI2 lower than 100 pmol/L, but inhibited by calcium channel blockers （verapamil and LaCI3）, calcineurin inhibitor （chlorpromazine, CPZ）, and polar auxin transport inhibitor （N-l-naphthylphthalamic acid, NPA）. Roots stopped growing and negative phototropism disappeared when the concentrations increased to 100 pmol/L verapamil, 12.500 ~Jmol/L LaCI3, 60 pmol/L CPZ, and 6 pmol/L NPA. Moreover, 100 pmol/L CaCI2 could relieve the inhibition of LaCI3, verapamil and NPA. The enhanced negative phototropism curvature was caused by the transportation of more auxin from the irradiated side to the shaded side in the presence of exogenous Ca2＋. Calcium signaling plays a key role as a second messenger in the process of light signal regulation of rice root growth and negative phototropism.展开更多
AIM:In order to explore whether the member of Bcl-2 gene family,for example,B cl-2 and Bax,are induced after cerebral ischemia,and whether expression of gene s can be modulated by calcium-antagonist.METHODS:The rat ce...AIM:In order to explore whether the member of Bcl-2 gene family,for example,B cl-2 and Bax,are induced after cerebral ischemia,and whether expression of gene s can be modulated by calcium-antagonist.METHODS:The rat cerebral ischemic mode ls were made by Nagasawa and Zea Longa improvement method,by occluding left midd le cerebral artery;the expression of Bcl-2 and Bax mRNA were measured by RT-PC R method.RESULTS:After administration of nimodipine, Bcl-2 mRNA was up-regulat ed in the hippocampus at 6 and 24 h after ischemia,while Bax mRNA was down-regu lated at 6 and 24h after ischemia.CONCLUSION:Calcium-antagonist can up-regulat e Bcl-2 mRNA and down-regulate Bax mRNA.Increasing the ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine.展开更多
Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on is...Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.展开更多
The purpose of this study is to demonstrate MCF-7 cells’ dependence on calcium for growth and to exploit that dependence to improve chemotherapy efficacy. Fura-2 fluorescence imaging shows that MCF-7 cells maintain a...The purpose of this study is to demonstrate MCF-7 cells’ dependence on calcium for growth and to exploit that dependence to improve chemotherapy efficacy. Fura-2 fluorescence imaging shows that MCF-7 cells maintain a higher basal intracellular calcium concentration than non-tumorigenic MCF-10A cells. Blocking T-type calcium channels with mibefradil reduced MCF-7 intracellular calcium concentration. Flow cytometry shows that knocking down T-type calcium channel expression with siRNA caused an increase in MCF-7 cells in G1 phase and a decrease in cells in S phase. Proliferation assays of MCF-7 cells treated with EGTA and thapsigargin reveal the dependence of MCF-7 cell growth on extracellular and intracellular calcium sources, respectively. In vitro, interlaced treatment that alternated the T-type calcium channel blocker NNC-55-0396 with paclitaxel more effectively reduced MCF-7 cell number than chemotherapy alone. In a mouse in vivo model, interlaced mibefradil and paclitaxel more effectively reduced MCF-7 xenograft size than chemotherapy alone. These findings indicate that MCF-7 cells are dependent on calcium for proliferation, particularly in passing the G1/S cell cycle checkpoint. Further, this dependence on calcium can be exploited by alternating treatment with T-type calcium channel blockers with paclitaxel in an interlaced therapy scheme that increases the efficacy of the chemotherapy.展开更多
Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easil...Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation,stroke,and myocardial infarction.The past decade has witnessed the rapid advances in the genetics of PA,which has shed new light on PA treatment.While surgery is the first choice for unilateral diseases,bilateral lesions can be treated with mineralocorticoid receptor antagonists(MRAs).The next-generation non-steroidal MRAs are under investigations.New medications including calcium channel blockers,macrophage antibiotics,and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.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 National Natural Science Foundation of China, No. 81171206
文摘Alzheimer＇s disease is characterized by two pathological hallmarks： amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer＇s disease. Calcium channel blockers are effective therapeutics for treating Alzheimer＇s disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer＇s disease theraov.
文摘Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.
文摘The release of mediators from mast cells is a model for cell secretion and is an in-vitro index for immediate hypersensitivity reactions. Calcium influx is generally accepted to be the primary biochemicalevent in mast cell activation.We studied the effect of the calcium ionophore A 23187 and calcium channelblockers,nifedipine and verapamil, in triggering the activation of rat peritoneal mast cells.At suitableconcentration nifedipine and verapamil have had the inhibition effect in the IgE-dependent roaction.
文摘\ The effects of tetrandrine (Tet) on cytosolic free calcium ([Ca2+]i) in subcultured bovine aortic smooth muscle cells (SMC) were studied by Fura2 and ARCMMIC cation measurement system. Tet (1～100 μmol·L-1) had no effect on the resting [Ca2+]i, but had inhibitory effects on [Ca2+]i elevation induced by high K+, 5HT, ATP, Ang II and NE in the presence of extracellular Ca2+. High concentration of Tet also inhibited Pheinduced [Ca2+]i elevation in absence of extracellular Ca2+. Tet (1～100 μmol·L-1) inhibited KCl (60 mmol·L-1) induced [Ca2+]i elevation in dosedependent manner, the IC50 value was 9.2 (95% confidence limits: 5.7～14.9) mmol·L-1. The results suggested that Tet had blocking effects on both VOC and ROC in bovine aortic SMC. It appears that the mechanisms of blocking effect of Tet on ROC might be primarily due to its Ca2+ entry blocking effects.
基金supported by the National Natural Science Foundation of China (Grant No. 31071353) the Open Fund of Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization of Huanggang Normal University, China (Grant Nos. 2013000503 and 2011BLKF243)
文摘Calcium ions （Ca2＋） act as an intracellular second messenger and affect nearly all aspects of cellular life. They are functioned by interacting with polar auxin transport, and the negative phototropism of plant roots is caused by the transport of auxin from the irradiated side to the shaded side of the roots. To clarify the role of calcium signaling in the modulation of rice root negative phototropism, as well as the relationship between polar auxin transport and calcium signaling, calcium signaling reagents were used to treat rice seminal roots which were cultivated in hydroculture and unilaterally illuminated at an intensity of 100-200 pmol/（m2.s） for 24 h. Negative phototropism curvature and growth rate of rice roots were both promoted by exogenous CaCI2 lower than 100 pmol/L, but inhibited by calcium channel blockers （verapamil and LaCI3）, calcineurin inhibitor （chlorpromazine, CPZ）, and polar auxin transport inhibitor （N-l-naphthylphthalamic acid, NPA）. Roots stopped growing and negative phototropism disappeared when the concentrations increased to 100 pmol/L verapamil, 12.500 ~Jmol/L LaCI3, 60 pmol/L CPZ, and 6 pmol/L NPA. Moreover, 100 pmol/L CaCI2 could relieve the inhibition of LaCI3, verapamil and NPA. The enhanced negative phototropism curvature was caused by the transportation of more auxin from the irradiated side to the shaded side in the presence of exogenous Ca2＋. Calcium signaling plays a key role as a second messenger in the process of light signal regulation of rice root growth and negative phototropism.
文摘AIM:In order to explore whether the member of Bcl-2 gene family,for example,B cl-2 and Bax,are induced after cerebral ischemia,and whether expression of gene s can be modulated by calcium-antagonist.METHODS:The rat cerebral ischemic mode ls were made by Nagasawa and Zea Longa improvement method,by occluding left midd le cerebral artery;the expression of Bcl-2 and Bax mRNA were measured by RT-PC R method.RESULTS:After administration of nimodipine, Bcl-2 mRNA was up-regulat ed in the hippocampus at 6 and 24 h after ischemia,while Bax mRNA was down-regu lated at 6 and 24h after ischemia.CONCLUSION:Calcium-antagonist can up-regulat e Bcl-2 mRNA and down-regulate Bax mRNA.Increasing the ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine.
文摘Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.
文摘The purpose of this study is to demonstrate MCF-7 cells’ dependence on calcium for growth and to exploit that dependence to improve chemotherapy efficacy. Fura-2 fluorescence imaging shows that MCF-7 cells maintain a higher basal intracellular calcium concentration than non-tumorigenic MCF-10A cells. Blocking T-type calcium channels with mibefradil reduced MCF-7 intracellular calcium concentration. Flow cytometry shows that knocking down T-type calcium channel expression with siRNA caused an increase in MCF-7 cells in G1 phase and a decrease in cells in S phase. Proliferation assays of MCF-7 cells treated with EGTA and thapsigargin reveal the dependence of MCF-7 cell growth on extracellular and intracellular calcium sources, respectively. In vitro, interlaced treatment that alternated the T-type calcium channel blocker NNC-55-0396 with paclitaxel more effectively reduced MCF-7 cell number than chemotherapy alone. In a mouse in vivo model, interlaced mibefradil and paclitaxel more effectively reduced MCF-7 xenograft size than chemotherapy alone. These findings indicate that MCF-7 cells are dependent on calcium for proliferation, particularly in passing the G1/S cell cycle checkpoint. Further, this dependence on calcium can be exploited by alternating treatment with T-type calcium channel blockers with paclitaxel in an interlaced therapy scheme that increases the efficacy of the chemotherapy.
基金Supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019XK320027).
文摘Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation,stroke,and myocardial infarction.The past decade has witnessed the rapid advances in the genetics of PA,which has shed new light on PA treatment.While surgery is the first choice for unilateral diseases,bilateral lesions can be treated with mineralocorticoid receptor antagonists(MRAs).The next-generation non-steroidal MRAs are under investigations.New medications including calcium channel blockers,macrophage antibiotics,and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.
