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
Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel bl...Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.展开更多
Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium chann...Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium channel blockers(CCBs),and beta-blockers.The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province,Wuhan,China.Clinical and laboratory characteristics were extracted from electronic medical records.Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records.The primary clinical endpoint was all-cause mortality.Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration.Logistic regression was used to explore the risk factors associated with mortality and prognosis.Propensity score matching was used to balance the confounders between different anti-hypertensive treatments.Kaplan-Meier curves were used to compare the cumulative recovery rate.Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19,31.7%(1449/4569)had a history of hypertension.There were significant differences in mortality rates between hypertensive patients with CCBs(7/359)and those without(21/359)(1.95%vs.5.85%,risk ratio[RR]:0.32,95% confidence interval[CI]:0.13–0.76,χ^(2)=7.61,P=0.0058).After matching for confounders,the mortality rates were similar between the RAAS inhibitor(4/236)and non-RAAS inhibitor(9/236)cohorts(1.69% vs.3.81%,RR:0.43,95% CI:0.13–1.43,χ^(2)=1.98,P=0.1596).Hypertensive patients with beta-blockers(13/340)showed no statistical difference in mortality compared with those without(11/340)(3.82% vs.3.24%,RR:1.19,95% CI:0.53–2.69,χ^(2)=0.17,P=0.6777).Conclusions:In our study,we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension,while CCBs could improve prognosis.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
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 effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (...The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (Isoc) in isolated rat hepatocytes after hepatic ischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC 50 value of 64.63±10.56 μmol/L (n=8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.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
The types of the voltage-dependent calcium channels (VDCCs) in human ejaculatory sperm and the effects of calcium channel blocker (CCB) on human sperm motility parameters in vitro were investigated. The human sper...The types of the voltage-dependent calcium channels (VDCCs) in human ejaculatory sperm and the effects of calcium channel blocker (CCB) on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine (NIF, inhibitor of L-type VDCC) and ω-conotoxin (GVIA, inhibitor of N-type VDCC) were compared and analyzed statistically. The results showed that NIF (1, 5, 10 μmol/L) could not only significantly affect human sperm's shape but also spermatozoa motility after incubated at least 10 rain in vitro (P〈0.001). GVIA (0.1, 0.5 and 1 μmol/L) could just only significantly affect human sperm's progressive motility (a %+b %) after incubated for 20 min in vitro (P〈0.01), but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.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
1 Transcatheter aortic valve implantation in symptomatic severe aortic stenosis: where do we stand? Aortic stenosis occurs in 2%-9% of patients over the age of 65, the most common cause being degenerative.^([1,2]) The...1 Transcatheter aortic valve implantation in symptomatic severe aortic stenosis: where do we stand? Aortic stenosis occurs in 2%-9% of patients over the age of 65, the most common cause being degenerative.^([1,2]) The preferred treatment in symptomatic severe aortic stenosis(SAS) is surgical aortic valve replacement(SAVR), but in the elderly, the surgical risk can be greater than the benefit.([3]).展开更多
Coronary artery spasm can cause recurrent variant angina with ST-segment elevation.The patient was asymptomatic with normal vitals and ECG was normal.We present a case associated with transient ST-segment elevation an...Coronary artery spasm can cause recurrent variant angina with ST-segment elevation.The patient was asymptomatic with normal vitals and ECG was normal.We present a case associated with transient ST-segment elevation and signifi-cant increase in troponin levels with non-critical lesion with normal CAG.展开更多
Fourteen outpatients (10 men, 4 women, mean age 52.6 yrs) suffered from essential hypertension complicated with left ventricular hypertrophy (LVH) detected by echocardiography were treated with Adalat 30 mg daily oral...Fourteen outpatients (10 men, 4 women, mean age 52.6 yrs) suffered from essential hypertension complicated with left ventricular hypertrophy (LVH) detected by echocardiography were treated with Adalat 30 mg daily orally. After 3 months administration, casual high blood pressue was satisfactorily controlled. Both thickness of inter ventricular septum and left ventricular posterior wall were decreased (1.47 cm vs 1.34 cm P<0.01, 1.43 cm vs 1.32 cm P<0.01). Left ventricular mass (LVM) and left ventricular mass index (LVMI) calculated according to Devereux corrective formula were significantly reversed (279.4 g vs 247.4 g P<0.01, 162.7 g/m 2 vs 146.5 g/m 2 P<0.01). Meanwhile, cardiac performance was assessed, and the results demonstrated that Adalat could maintain left ventricular systolic function and improve left ventricular diastolic function which was resulted from regression of LVH. No side effects of Adalat were present in the study patients.展开更多
Background:Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD).We carried out a meta-analysis to...Background:Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD).We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e.,ACEI/ARB + CCB) with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods:Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease (ESRD),cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate (GFR),and adverse events were extracted.Results:Based on seven RCTs with 628 patients,ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] =0.84;95% confidence interval [CI]:0.52-1.33) and cardiovascular events (RR =0.58;95% CI:0.21-1.63) significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] =-1.28 mmHg;95% CI:-3.18 to-0.62),proteinuria (standard mean difference =-0.55;95% CI:-1.41 to-0.30),GFR (WMD =-0.32 ml/min;95% CI:-1.53 to-0.89),and occurrence of adverse events (RR =1.05;95% CI:0.72-1.53).However,ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD =-4.46 mmHg;95% CI:-6.95 to-1.97),compared with ACEI/ARB monotherapy.Conclusion:ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.展开更多
Drug-induced gingival overgrowth(DIGO)is a pathological growth of gingival tissue,primarily associated with calcium channel blockers and immunosuppressants.Consequently,it is mainly seen in cardiovascular and transpla...Drug-induced gingival overgrowth(DIGO)is a pathological growth of gingival tissue,primarily associated with calcium channel blockers and immunosuppressants.Consequently,it is mainly seen in cardiovascular and transplanted patients.Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect.As for immunosuppress-ants,cyclosporin is the leading causative agent,whereas other drugs from this druggroup,including tacrolimus,have better safety profiles.Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition.Several factors are involved in the pathogenesis and can increase the risk,such as male gender,younger age,pre-existing periodontal inflammation,and concomitant use of other DIGO-inducing medications.Patients with DIGO may experience severe discomfort,trouble with speech and mastication,pain,and teeth loss,aside from cosmetic implications.Furthermore,these patients also have an increased risk for cardiovascular diseases.The interdisciplinary approach and cooperation with dental care experts are necessary for patient management.Treatment includes discontinuing the drug and switching to one with a better profile,improving oral hygiene,and surgical removal of enlarged tissue.Recognizing the potential of commonly used medications to cause DIGO and its effect on patients'health is necessary for early detection and adequate management of this complication.展开更多
Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with t...Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with the help of P-glycoprotein(Pgp)-a drug efflux pump.It has also been observed that overexpressed T-type calcium channels(TTCCs)maintain calcium homeostasis in cancer cells,and calcium has a role in chemoresistance.Therefore,the aim of this study was to test the adjuvant role of TTA-A2,a TTCC blocker,in enhancing the anticancer effect of PTX on the A549 lung adenocarcinoma cell line.Methods:Morphology assay,calcium imaging assay,clonogenic assay,apoptosis assay,and real-time polymerase chain reaction(real-time PCR)were performed to find the adjuvant role of TTA-A2.Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations.PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations,respectively.Results:Immunocytochemistry confirmed the expression of TTCC in A549 cells.Morphology assay showed altered morphology of A549 cells.The adjuvant role of TTA-A2 was observed in the calcium imaging assay in spheroids,in the clonogenic assay in monolayers,and in the apoptosis assay in both cultures.With real-time PCR,it was observed that,even though cells express the mRNA of Pgp,it is non-significant upon treatment with PTX and TTA-A2.Conclusion:TTA-A2 can be used as an adjuvant to reduce chemoresistance in cancer cells as well as to enhance the anticancer effect of the standard anticancer drug PTX.Being a potent TTCC inhibitor,TTA-A2 may also enhance the anticancer effects of other anticancer drugs.展开更多
Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methan...Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.展开更多
Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradu...Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradual increase of VER concentration in the media. MTT method was used to assay resistance to VER, cross resistance to dipyriamole (DPM), cyclosporin A (CsA) in the cells, and HPLC and spectrofluorometer to detect intracellular accumulation of VER or ADM respectively, as well as S-P immunocytochemical technique for detection of genes expression. Results: It were observed that 7.9—fold increase in VER resistance, significantly reduced intracellular accumulation of VER or ADM and also develop across resistance to DPM and CsA in K562/ADM/VER cells, compared with its parent cell, K562/ADM. High-level of p-glycoprotein(pgp), middle-level of p53, p16, was present in two cell lines without expression of GSTPI, C-myc, C-myc, C-fos and C-erbB-2. Bc1–2 protein expression was found only in K562/ADM cells. Conclusion: K562/ADM cells were capable of being induced to develop resistance to VER.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 unsatisfactory results of clinical trials with class-Ⅰ antiarrhythmic drugs have prompted a renaissance of interest in compounds with class-Ⅲ antiarrhythmic action. In the present, we have reevaluated the class-...The unsatisfactory results of clinical trials with class-Ⅰ antiarrhythmic drugs have prompted a renaissance of interest in compounds with class-Ⅲ antiarrhythmic action. In the present, we have reevaluated the class-Ⅲ antiarrhythmic ef-展开更多
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Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.
基金supported by grants from the Natural Science Foundation of Shanghai(No.15ZR1412300)Three-Year Action Plan for Strengthening Public Health System in Shanghai(2020–2022)Key Discipline Con-struction Project(No.GWV-10.1-XK05).
文摘Background:Hypertension is considered an important risk factor for the coronavirus disease 2019(COVID-19).The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system(RAAS)inhibitors,calcium channel blockers(CCBs),and beta-blockers.The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province,Wuhan,China.Clinical and laboratory characteristics were extracted from electronic medical records.Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records.The primary clinical endpoint was all-cause mortality.Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration.Logistic regression was used to explore the risk factors associated with mortality and prognosis.Propensity score matching was used to balance the confounders between different anti-hypertensive treatments.Kaplan-Meier curves were used to compare the cumulative recovery rate.Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19,31.7%(1449/4569)had a history of hypertension.There were significant differences in mortality rates between hypertensive patients with CCBs(7/359)and those without(21/359)(1.95%vs.5.85%,risk ratio[RR]:0.32,95% confidence interval[CI]:0.13–0.76,χ^(2)=7.61,P=0.0058).After matching for confounders,the mortality rates were similar between the RAAS inhibitor(4/236)and non-RAAS inhibitor(9/236)cohorts(1.69% vs.3.81%,RR:0.43,95% CI:0.13–1.43,χ^(2)=1.98,P=0.1596).Hypertensive patients with beta-blockers(13/340)showed no statistical difference in mortality compared with those without(11/340)(3.82% vs.3.24%,RR:1.19,95% CI:0.53–2.69,χ^(2)=0.17,P=0.6777).Conclusions:In our study,we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension,while CCBs could improve prognosis.
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.
基金This project was supported by the National Natural Sci ence Foundation of China (No. 30270532), the Trans Cen tury Excellent Talent Development Plan Fund of Ministry ofEducation of China (Official Letter No. 2002 48) and Shu guang Program Project of Shanghai Educational Committee(No. 02SG20).
文摘The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on store-operated calcium current (Isoc) in isolated rat hepatocytes after hepatic ischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC 50 value of 64.63±10.56 μmol/L (n=8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.
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The types of the voltage-dependent calcium channels (VDCCs) in human ejaculatory sperm and the effects of calcium channel blocker (CCB) on human sperm motility parameters in vitro were investigated. The human sperm motility parameters in vitro in response to the pharmacological agents nifedipine (NIF, inhibitor of L-type VDCC) and ω-conotoxin (GVIA, inhibitor of N-type VDCC) were compared and analyzed statistically. The results showed that NIF (1, 5, 10 μmol/L) could not only significantly affect human sperm's shape but also spermatozoa motility after incubated at least 10 rain in vitro (P〈0.001). GVIA (0.1, 0.5 and 1 μmol/L) could just only significantly affect human sperm's progressive motility (a %+b %) after incubated for 20 min in vitro (P〈0.01), but they both could not significantly affect spermic abnormality rate. It is suggested that L-type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane of human sperm solely or together, and they participate in the spermic physiological processes especially the spermic motility.
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.
文摘1 Transcatheter aortic valve implantation in symptomatic severe aortic stenosis: where do we stand? Aortic stenosis occurs in 2%-9% of patients over the age of 65, the most common cause being degenerative.^([1,2]) The preferred treatment in symptomatic severe aortic stenosis(SAS) is surgical aortic valve replacement(SAVR), but in the elderly, the surgical risk can be greater than the benefit.([3]).
基金the Natural Science Foundation of Shandong Province(ZR2017BH114)the National Natural Science Foundation of China(81700334)Jinan Science and Technology Plan Project(201805058).
文摘Coronary artery spasm can cause recurrent variant angina with ST-segment elevation.The patient was asymptomatic with normal vitals and ECG was normal.We present a case associated with transient ST-segment elevation and signifi-cant increase in troponin levels with non-critical lesion with normal CAG.
文摘Fourteen outpatients (10 men, 4 women, mean age 52.6 yrs) suffered from essential hypertension complicated with left ventricular hypertrophy (LVH) detected by echocardiography were treated with Adalat 30 mg daily orally. After 3 months administration, casual high blood pressue was satisfactorily controlled. Both thickness of inter ventricular septum and left ventricular posterior wall were decreased (1.47 cm vs 1.34 cm P<0.01, 1.43 cm vs 1.32 cm P<0.01). Left ventricular mass (LVM) and left ventricular mass index (LVMI) calculated according to Devereux corrective formula were significantly reversed (279.4 g vs 247.4 g P<0.01, 162.7 g/m 2 vs 146.5 g/m 2 P<0.01). Meanwhile, cardiac performance was assessed, and the results demonstrated that Adalat could maintain left ventricular systolic function and improve left ventricular diastolic function which was resulted from regression of LVH. No side effects of Adalat were present in the study patients.
文摘Background:Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD).We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e.,ACEI/ARB + CCB) with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods:Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease (ESRD),cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate (GFR),and adverse events were extracted.Results:Based on seven RCTs with 628 patients,ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] =0.84;95% confidence interval [CI]:0.52-1.33) and cardiovascular events (RR =0.58;95% CI:0.21-1.63) significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] =-1.28 mmHg;95% CI:-3.18 to-0.62),proteinuria (standard mean difference =-0.55;95% CI:-1.41 to-0.30),GFR (WMD =-0.32 ml/min;95% CI:-1.53 to-0.89),and occurrence of adverse events (RR =1.05;95% CI:0.72-1.53).However,ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD =-4.46 mmHg;95% CI:-6.95 to-1.97),compared with ACEI/ARB monotherapy.Conclusion:ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.
文摘Drug-induced gingival overgrowth(DIGO)is a pathological growth of gingival tissue,primarily associated with calcium channel blockers and immunosuppressants.Consequently,it is mainly seen in cardiovascular and transplanted patients.Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect.As for immunosuppress-ants,cyclosporin is the leading causative agent,whereas other drugs from this druggroup,including tacrolimus,have better safety profiles.Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition.Several factors are involved in the pathogenesis and can increase the risk,such as male gender,younger age,pre-existing periodontal inflammation,and concomitant use of other DIGO-inducing medications.Patients with DIGO may experience severe discomfort,trouble with speech and mastication,pain,and teeth loss,aside from cosmetic implications.Furthermore,these patients also have an increased risk for cardiovascular diseases.The interdisciplinary approach and cooperation with dental care experts are necessary for patient management.Treatment includes discontinuing the drug and switching to one with a better profile,improving oral hygiene,and surgical removal of enlarged tissue.Recognizing the potential of commonly used medications to cause DIGO and its effect on patients'health is necessary for early detection and adequate management of this complication.
基金This work was supported by Impacting Research Innovation and Technology(project code:5450)University Grant Commission fellowship(Ref.no.21/12/2014(ii)EU-V)。
文摘Aim:Chemoresistance is a prevalent issue in cancer treatment.Paclitaxel(PTX)is a microtubule-binding anticancer drug used in various cancer treatments.However,cancer cells often show chemoresistance against PTX with the help of P-glycoprotein(Pgp)-a drug efflux pump.It has also been observed that overexpressed T-type calcium channels(TTCCs)maintain calcium homeostasis in cancer cells,and calcium has a role in chemoresistance.Therefore,the aim of this study was to test the adjuvant role of TTA-A2,a TTCC blocker,in enhancing the anticancer effect of PTX on the A549 lung adenocarcinoma cell line.Methods:Morphology assay,calcium imaging assay,clonogenic assay,apoptosis assay,and real-time polymerase chain reaction(real-time PCR)were performed to find the adjuvant role of TTA-A2.Samples were treated with PTX at 10 nM concentration and TTA-A2 at 50 and 100 nM concentrations.PTX and TTA-A2 were used in the combination treatment at 10 and 100 nM concentrations,respectively.Results:Immunocytochemistry confirmed the expression of TTCC in A549 cells.Morphology assay showed altered morphology of A549 cells.The adjuvant role of TTA-A2 was observed in the calcium imaging assay in spheroids,in the clonogenic assay in monolayers,and in the apoptosis assay in both cultures.With real-time PCR,it was observed that,even though cells express the mRNA of Pgp,it is non-significant upon treatment with PTX and TTA-A2.Conclusion:TTA-A2 can be used as an adjuvant to reduce chemoresistance in cancer cells as well as to enhance the anticancer effect of the standard anticancer drug PTX.Being a potent TTCC inhibitor,TTA-A2 may also enhance the anticancer effects of other anticancer drugs.
文摘Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.
文摘Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradual increase of VER concentration in the media. MTT method was used to assay resistance to VER, cross resistance to dipyriamole (DPM), cyclosporin A (CsA) in the cells, and HPLC and spectrofluorometer to detect intracellular accumulation of VER or ADM respectively, as well as S-P immunocytochemical technique for detection of genes expression. Results: It were observed that 7.9—fold increase in VER resistance, significantly reduced intracellular accumulation of VER or ADM and also develop across resistance to DPM and CsA in K562/ADM/VER cells, compared with its parent cell, K562/ADM. High-level of p-glycoprotein(pgp), middle-level of p53, p16, was present in two cell lines without expression of GSTPI, C-myc, C-myc, C-fos and C-erbB-2. Bc1–2 protein expression was found only in K562/ADM cells. Conclusion: K562/ADM cells were capable of being induced to develop resistance to VER.
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 unsatisfactory results of clinical trials with class-Ⅰ antiarrhythmic drugs have prompted a renaissance of interest in compounds with class-Ⅲ antiarrhythmic action. In the present, we have reevaluated the class-Ⅲ antiarrhythmic ef-