Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and es...Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and esophageal mucosal damage in gastro-esophageal reflux disease (GERD) are related to the degree of acid exposure, K+ is a logical target for approaches to inhibit acid production.The probable K+ binding site on the gastric H+,K+-ATPase has recently been described and studies are elucidating how K+ activates the enzyme. K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified. The channels represent theoretical sites for agents to control acid secretion but it will be difficult to develop selective blockers. An alternative strategy is to prevent K+ from activating gastric H+,K+-ATPase; the potassiumcompetitive acid blocker (P-CAB) class inhibits acidsecretion by binding at or near the K+ binding site.Ongoing research is further defining the role of K+ in the functioning of the gastric H+,K+-ATPase, as well as determining the clinical utility of agents directed toward this important cation.展开更多
Since the calcium channel blocker （CCB） has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydrop...Since the calcium channel blocker （CCB） has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine （DHP） CCB, addressing pharmacological mecha- nisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.展开更多
AIM： To evaluate the risk factors-other than nonsteroidal anti-inflammatory drugs-for colonic diverticular bleeding in a westernized population. METHODS： One hundred and forty patients, treated for symptomatic diver...AIM： To evaluate the risk factors-other than nonsteroidal anti-inflammatory drugs-for colonic diverticular bleeding in a westernized population. METHODS： One hundred and forty patients, treated for symptomatic diverticular disease in a community based hospital, were included. Thirty （21%） had signs of diverticular bleeding. Age, gender, and the results of colonoscopy were collected and compared to a group of patients with nonbleeding symptomatic diverticulosis. Records were reviewed for comorbidities, such as obesity, alcohol consumption, smoking habits and metabolic diseases. Special emphasis was put on arterial hypertension, cardiovascular events, diabetes mellitus, hyperuricemia and hypercholesterinemia. RESULTS： There was no difference between patients with diverticular hemorrhage and those with nonbleeding symptomatic diverticulosis regarding gender ratio （male/female 9/21 vs 47/63） and diverticular Iocalisation. Bleeding patients differed in respect to age （73.4± 9.9 vs 67. 8± 13.0, P 〈 0.013）. Significant differences were found between both groups regarding the presence of hyperuricemia and use of steroids and nonsteroidal anti-inflammatory drugs. Patients with three concomitant metabolic diseases were also identified as being at risk of bleeding. A forward stepwise logistic regression analysis revealed steroids, hyperuricemia and the use of calcium-channel blockers as independent risk factors of bleeding.CONCLUSION： Beside nonsteroidal anti-inflammatory steroid drug use, antihypertensive medication and concomitant arteriosclerotic diseases are risk factors for colonic diverticular hemorrhage. Our results support the hypothesis of an altered arteriosclerotic vessel as the source of bleeding.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:Cardiovascular diseases are associated with an increased risk of depression,but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk.The effects of drugs on indivi...Objective:Cardiovascular diseases are associated with an increased risk of depression,but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk.The effects of drugs on individual usage are also often unknown.This review aimed to examine the correlation between depression and common cardiovascular drugs,develop more potent interventions for depression in cardiovascular patients,and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.Data sources:The data in this review were obtained from articles included in PubMed,EMBASE,and Web of Science.Study selection:Clinical trials,observational studies,review literature,and guidelines about depression and cardiovascular drugs were selected for the article.Results:We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review.Statins have been proven to have antidepressant effects.Some studies believe angiotensin-converting enzyme inhibitors(ACEIs)/angiotensin receptor blocker(ARB)can exert an antidepressant influence by acting on the renin-angiotensin system,but further clinical trials are needed to confirm this.Beta-blockers have previously been associated with depression,but the current study found no significant association between beta blockers and the risk of depression.Aspirin may have antidepressant effects by suppressing the immune response,but its role as an antidepressant remains controversial.calcium channel blockers(CCBs)can regulate nerve signal transduction by adjusting calcium channels,but whether this effect is beneficial or harmful to depression remains unclear.Finally,some cases have reported that nitrates and diuretics are associated with depression,but the current clinical evidence is insufficient.Conclusions:Statins have been proven to have antidepressant effect,and the antidepressant effects of ACEIs/ARB and aspirin are still controversial.CCBs are associated with depre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
文摘Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and esophageal mucosal damage in gastro-esophageal reflux disease (GERD) are related to the degree of acid exposure, K+ is a logical target for approaches to inhibit acid production.The probable K+ binding site on the gastric H+,K+-ATPase has recently been described and studies are elucidating how K+ activates the enzyme. K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified. The channels represent theoretical sites for agents to control acid secretion but it will be difficult to develop selective blockers. An alternative strategy is to prevent K+ from activating gastric H+,K+-ATPase; the potassiumcompetitive acid blocker (P-CAB) class inhibits acidsecretion by binding at or near the K+ binding site.Ongoing research is further defining the role of K+ in the functioning of the gastric H+,K+-ATPase, as well as determining the clinical utility of agents directed toward this important cation.
文摘Since the calcium channel blocker （CCB） has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine （DHP） CCB, addressing pharmacological mecha- nisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.
文摘AIM： To evaluate the risk factors-other than nonsteroidal anti-inflammatory drugs-for colonic diverticular bleeding in a westernized population. METHODS： One hundred and forty patients, treated for symptomatic diverticular disease in a community based hospital, were included. Thirty （21%） had signs of diverticular bleeding. Age, gender, and the results of colonoscopy were collected and compared to a group of patients with nonbleeding symptomatic diverticulosis. Records were reviewed for comorbidities, such as obesity, alcohol consumption, smoking habits and metabolic diseases. Special emphasis was put on arterial hypertension, cardiovascular events, diabetes mellitus, hyperuricemia and hypercholesterinemia. RESULTS： There was no difference between patients with diverticular hemorrhage and those with nonbleeding symptomatic diverticulosis regarding gender ratio （male/female 9/21 vs 47/63） and diverticular Iocalisation. Bleeding patients differed in respect to age （73.4± 9.9 vs 67. 8± 13.0, P 〈 0.013）. Significant differences were found between both groups regarding the presence of hyperuricemia and use of steroids and nonsteroidal anti-inflammatory drugs. Patients with three concomitant metabolic diseases were also identified as being at risk of bleeding. A forward stepwise logistic regression analysis revealed steroids, hyperuricemia and the use of calcium-channel blockers as independent risk factors of bleeding.CONCLUSION： Beside nonsteroidal anti-inflammatory steroid drug use, antihypertensive medication and concomitant arteriosclerotic diseases are risk factors for colonic diverticular hemorrhage. Our results support the hypothesis of an altered arteriosclerotic vessel as the source of bleeding.
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.
基金the grants from the National Natural Science Foundation of China(No.81970447)China Women’s Development Foundation(No.2019300).
文摘Objective:Cardiovascular diseases are associated with an increased risk of depression,but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk.The effects of drugs on individual usage are also often unknown.This review aimed to examine the correlation between depression and common cardiovascular drugs,develop more potent interventions for depression in cardiovascular patients,and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.Data sources:The data in this review were obtained from articles included in PubMed,EMBASE,and Web of Science.Study selection:Clinical trials,observational studies,review literature,and guidelines about depression and cardiovascular drugs were selected for the article.Results:We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review.Statins have been proven to have antidepressant effects.Some studies believe angiotensin-converting enzyme inhibitors(ACEIs)/angiotensin receptor blocker(ARB)can exert an antidepressant influence by acting on the renin-angiotensin system,but further clinical trials are needed to confirm this.Beta-blockers have previously been associated with depression,but the current study found no significant association between beta blockers and the risk of depression.Aspirin may have antidepressant effects by suppressing the immune response,but its role as an antidepressant remains controversial.calcium channel blockers(CCBs)can regulate nerve signal transduction by adjusting calcium channels,but whether this effect is beneficial or harmful to depression remains unclear.Finally,some cases have reported that nitrates and diuretics are associated with depression,but the current clinical evidence is insufficient.Conclusions:Statins have been proven to have antidepressant effect,and the antidepressant effects of ACEIs/ARB and aspirin are still controversial.CCBs are associated with depre
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.
文摘目的 了解维持性血液透析（血透）患者高血压的患病和治疗情况,为血透患者的高血压诊断和治疗提供依据.方法 对上海市11家透析中心的1382例维持性血透患者进行横断面调查,其中男性809例,女性573例.结果 （1）本次受访的维持性血透患者高血压患病率为86.3%,治疗率96.8%,控制率[血透前血压＜140/90 mm Hg（1 mm Hg=0.133 kPa）]25.5%;（2）50.4%患者应用一种降压药,应用2、3和4种或以上者占34.4%、14.2%和1.0%.单药用药以钙通道阻滞剂为多（61.0%）,血管紧张素Ⅱ受体拮抗剂和血管紧张素转换酶抑制剂分别为56.4%和6.4%,中枢性降压药物为26.4%,β或α、β阻滞剂为14.0%.联合用药以钙通道阻滞剂联合血管紧张素Ⅱ受体拮抗剂最常用（63.2%）;（3）冠心病、透析充分性和用药数量影响血透患者的高血压控制率,冠心病以及联合用药者高血压控制更困难,而充分透析有助于提高高血压控制率.结论 维持性血透患者中高血压极为常见,患病率和治疗率均较高,但控制率很低,降压药物的联合应用不够.维持性血透患者的血压控制情况受透析充分性、心脏疾病、降压药物使用情况等多种因素影响.
