AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in w...AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.展开更多
背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物...背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物相关的单核苷酸多态性以及骨密度相关数据。主要分析方法是逆方差加权法,同时也使用了加权中位数法、简单中位数法、加权中值方法和MR-Egger回归法。使用β值和95%CI来评估他汀类药物与骨密度之间的因果关系;另外,进行敏感性分析以验证结果的可靠性,使用Cochran’s Q检验来评估异质性,使用MR-Egger截距检验是否存在水平多效性。使用留一法分析确定是否有单个或多个单核苷酸多态性影响了结果。结果与结论:他汀类药物作用靶点——3-羟基-3-甲基戊二酰辅酶A还原酶介导的低密度脂蛋白胆固醇与足跟定量超声骨密度(β=-0.086,95%CI:-0.117至-0.055,P=5.42×10^(-8))和全身骨密度(β=-0.193,95%CI:-0.288至-0.098,P=7.35×10^(-5))呈显著相关。该研究结果支持了他汀类药物对骨密度的保护作用。这些发现不仅加深了对胆固醇相关基因和骨骼健康关系的理解,还揭示了改善骨密度的潜在治疗靶点。展开更多
AIM:To examine the association between statin use and the development of esophageal cancer METHODS:We performed a systematic review and meta-analysis.Multiple databases(Pubmed,EMBASE,Cochrane Library,Web of Science,Wi...AIM:To examine the association between statin use and the development of esophageal cancer METHODS:We performed a systematic review and meta-analysis.Multiple databases(Pubmed,EMBASE,Cochrane Library,Web of Science,Wiley Interscience and Google Scholar) were systematically searched for studies reporting the association of statin use and the development of esophageal cancer.Literature searching and data abstraction were performed independently by two separate researchers.The quality of studies reviewed was evaluated using the Newcastle-Ottawa Quality assessment scale.Meta-analysis on the relationship between statin use and cancer incidence was performed.The effect of the combination of statin plus a cyclo-oxygenase inhibitor was also examined.RESULTS:Eleven studies met eligibility criteria,9 high and 2 medium quality.All were observational studies.Studies examining adenocarcinoma development in Barrett's esophagus included 317 cancers and 1999 controls,population-based studies examining all esophageal cancers included 371203 cancers and 6083150 controls.In the Barrett's population the use of statins(OR = 0.57;95%CI:0.43-0.75) and cyclo-oxygenase inhibitors(OR = 0.59;95%CI:0.45-0.77) were independently associated with a reduced incidence of adenocarcinoma.Combined use of a statin plus cyclooxygenase inhibitor was associated with an even lower adenocarcinoma incidence(OR = 0.26;95%CI:0.1-0.68).There was more heterogeneity in the population-based studies but pooled adjusted data showed that statin use was associated with a lower incidence of all combined esophageal cancers(OR = 0.81;95%CI:0.75-0.88).CONCLUSION:Statin use in patients with Barrett's oesophagus is associated with a significantly lower incidence of adenocarcinoma.The chemopreventive actions of statins,especially combined with cyclooxygenase inhibitors deserve further exploration.展开更多
The incidence of esophageal adenocarcinoma,a poor prognosis neoplasia,has risen dramatically in recent decades.Barrett’s esophagus represents the best-known risk factor for esophageal adenocarcinoma development.Non-s...The incidence of esophageal adenocarcinoma,a poor prognosis neoplasia,has risen dramatically in recent decades.Barrett’s esophagus represents the best-known risk factor for esophageal adenocarcinoma development.Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation,increase cell apoptosis and regulate the expression of growth and angiogenic factors.Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades.At present,epidemiological studies are small and underpowered.Their data could not justify either medication as a chemo-preventive agent.Population based studies have shown a 43%reduction of the odds of developing an esophageal adenocarcinoma,leaving out or stating a 25%reduction in patients consuming non-aspirin nonsteroidal antiinflammatory drugs and a 50%reduction in those patients consuming aspirin.They have also stated a 19%reduction of esophageal cancer incidence when statins have been used.Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce theadenocarcinoma incidence in patients with Barrett’s esophagus by 41%,while statins could reduce the risk by 43%.The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins(a 74%decrease).Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses.Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity,while statins are rather safe drugs.In conclusion,both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies.In the meanwhile,their use is justified only in patients with cardiovascular disease.展开更多
A potential dual inhibitor（4） for exogenous absorption and endogenic synthesis of cholesterol was designed based on the conjugation of the β-lactam pharmacophore of ezetimibe and the δ-lactone pharmacophore of sta...A potential dual inhibitor（4） for exogenous absorption and endogenic synthesis of cholesterol was designed based on the conjugation of the β-lactam pharmacophore of ezetimibe and the δ-lactone pharmacophore of statins. The merger of ezetimibe and statin 4 was synthesized from p-hydroxybenzaldehyde through a ten-step route. 1H NMR analysis showed existence of four pairs of enantiomers（5.7：5.7：1：1, molar ratio）. And compound 4 was found to lower total glucose（TG） level in rat serum via a high-cholesterol and high-fat feeding experiment.展开更多
Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable an...Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable and clinically introduced non-antifungal drugs,which have potent antifungal activity.Statins were originally used as cholesterol lowering agents in human therapy,but recent studies demonstrated their in vitro antifungal activity against yeasts and filamentous fungi.This indicated their potential application,alone or in combination with other drugs,in the treatment of such diseases.Their effective concentrations are higher than their maximum achievable serum levels;therefore,the application of statins for the treatment of invasive fungal infections is only possible in combination with antifungal agents.These synergistic combinations establish a basis for a new safely applicable therapy.This review focuses on the antifungal activity of statins alone and in combination with antifungal and non-antifungal drugs,and their possible application in clinical therapy.展开更多
Dose is one of the parameters that any pharmacologist seriously considers when studying the effects of a drug.If the necessary dose to achieve a desired pharmacological effect is in a toxic or very toxic range for hum...Dose is one of the parameters that any pharmacologist seriously considers when studying the effects of a drug.If the necessary dose to achieve a desired pharmacological effect is in a toxic or very toxic range for human use,the drug will probably fall out from further research.The concentration that a drug can reach to its target organ or cell is a direct consequence of the administered dose and its pharmacodynamic properties.Basic researchers investigate at the cellular level or eventually with xenografts.They use different concentrations of the drug in order to determine its cellular effects.However,in many cases,these concentrations require doses that are in the toxic range or well beyond any clinically achievable level.Therefore,in these cases,research is in the realm of toxicology rather than therapeutics.This paper will show some examples about this exercise in futility which is time and resource consuming but that pullulates the pages of many prestigious journals.Many seasoned researchers seem to have forgotten the Paracelsus Paradox.展开更多
文摘AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.
文摘背景:观察性研究表明他汀类药物可能对骨密度具有保护作用,这使其成为潜在的骨质疏松症治疗药物之一。目的:通过孟德尔随机化方法来评估药物靶点介导的脂质表型与骨密度之间的因果关系。方法:从IEU Open GWAS数据库获取了与他汀类药物相关的单核苷酸多态性以及骨密度相关数据。主要分析方法是逆方差加权法,同时也使用了加权中位数法、简单中位数法、加权中值方法和MR-Egger回归法。使用β值和95%CI来评估他汀类药物与骨密度之间的因果关系;另外,进行敏感性分析以验证结果的可靠性,使用Cochran’s Q检验来评估异质性,使用MR-Egger截距检验是否存在水平多效性。使用留一法分析确定是否有单个或多个单核苷酸多态性影响了结果。结果与结论:他汀类药物作用靶点——3-羟基-3-甲基戊二酰辅酶A还原酶介导的低密度脂蛋白胆固醇与足跟定量超声骨密度(β=-0.086,95%CI:-0.117至-0.055,P=5.42×10^(-8))和全身骨密度(β=-0.193,95%CI:-0.288至-0.098,P=7.35×10^(-5))呈显著相关。该研究结果支持了他汀类药物对骨密度的保护作用。这些发现不仅加深了对胆固醇相关基因和骨骼健康关系的理解,还揭示了改善骨密度的潜在治疗靶点。
文摘AIM:To examine the association between statin use and the development of esophageal cancer METHODS:We performed a systematic review and meta-analysis.Multiple databases(Pubmed,EMBASE,Cochrane Library,Web of Science,Wiley Interscience and Google Scholar) were systematically searched for studies reporting the association of statin use and the development of esophageal cancer.Literature searching and data abstraction were performed independently by two separate researchers.The quality of studies reviewed was evaluated using the Newcastle-Ottawa Quality assessment scale.Meta-analysis on the relationship between statin use and cancer incidence was performed.The effect of the combination of statin plus a cyclo-oxygenase inhibitor was also examined.RESULTS:Eleven studies met eligibility criteria,9 high and 2 medium quality.All were observational studies.Studies examining adenocarcinoma development in Barrett's esophagus included 317 cancers and 1999 controls,population-based studies examining all esophageal cancers included 371203 cancers and 6083150 controls.In the Barrett's population the use of statins(OR = 0.57;95%CI:0.43-0.75) and cyclo-oxygenase inhibitors(OR = 0.59;95%CI:0.45-0.77) were independently associated with a reduced incidence of adenocarcinoma.Combined use of a statin plus cyclooxygenase inhibitor was associated with an even lower adenocarcinoma incidence(OR = 0.26;95%CI:0.1-0.68).There was more heterogeneity in the population-based studies but pooled adjusted data showed that statin use was associated with a lower incidence of all combined esophageal cancers(OR = 0.81;95%CI:0.75-0.88).CONCLUSION:Statin use in patients with Barrett's oesophagus is associated with a significantly lower incidence of adenocarcinoma.The chemopreventive actions of statins,especially combined with cyclooxygenase inhibitors deserve further exploration.
文摘The incidence of esophageal adenocarcinoma,a poor prognosis neoplasia,has risen dramatically in recent decades.Barrett’s esophagus represents the best-known risk factor for esophageal adenocarcinoma development.Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation,increase cell apoptosis and regulate the expression of growth and angiogenic factors.Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades.At present,epidemiological studies are small and underpowered.Their data could not justify either medication as a chemo-preventive agent.Population based studies have shown a 43%reduction of the odds of developing an esophageal adenocarcinoma,leaving out or stating a 25%reduction in patients consuming non-aspirin nonsteroidal antiinflammatory drugs and a 50%reduction in those patients consuming aspirin.They have also stated a 19%reduction of esophageal cancer incidence when statins have been used.Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce theadenocarcinoma incidence in patients with Barrett’s esophagus by 41%,while statins could reduce the risk by 43%.The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins(a 74%decrease).Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses.Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity,while statins are rather safe drugs.In conclusion,both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies.In the meanwhile,their use is justified only in patients with cardiovascular disease.
基金Supported by the Grant from the Bureau of Science and Technology of Changchun City China(No.2005132)
文摘A potential dual inhibitor（4） for exogenous absorption and endogenic synthesis of cholesterol was designed based on the conjugation of the β-lactam pharmacophore of ezetimibe and the δ-lactone pharmacophore of statins. The merger of ezetimibe and statin 4 was synthesized from p-hydroxybenzaldehyde through a ten-step route. 1H NMR analysis showed existence of four pairs of enantiomers（5.7：5.7：1：1, molar ratio）. And compound 4 was found to lower total glucose（TG） level in rat serum via a high-cholesterol and high-fat feeding experiment.
基金Supported by PannonPharma(Pécsvárad,Hungary)the Hungarian Scientific Research Fund(OTKA),No.PD 83355(to Galgóczy L).
文摘Fungal infections are increasing and their treatment is difficult,because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore,interest has focused on safely applicable and clinically introduced non-antifungal drugs,which have potent antifungal activity.Statins were originally used as cholesterol lowering agents in human therapy,but recent studies demonstrated their in vitro antifungal activity against yeasts and filamentous fungi.This indicated their potential application,alone or in combination with other drugs,in the treatment of such diseases.Their effective concentrations are higher than their maximum achievable serum levels;therefore,the application of statins for the treatment of invasive fungal infections is only possible in combination with antifungal agents.These synergistic combinations establish a basis for a new safely applicable therapy.This review focuses on the antifungal activity of statins alone and in combination with antifungal and non-antifungal drugs,and their possible application in clinical therapy.
文摘Dose is one of the parameters that any pharmacologist seriously considers when studying the effects of a drug.If the necessary dose to achieve a desired pharmacological effect is in a toxic or very toxic range for human use,the drug will probably fall out from further research.The concentration that a drug can reach to its target organ or cell is a direct consequence of the administered dose and its pharmacodynamic properties.Basic researchers investigate at the cellular level or eventually with xenografts.They use different concentrations of the drug in order to determine its cellular effects.However,in many cases,these concentrations require doses that are in the toxic range or well beyond any clinically achievable level.Therefore,in these cases,research is in the realm of toxicology rather than therapeutics.This paper will show some examples about this exercise in futility which is time and resource consuming but that pullulates the pages of many prestigious journals.Many seasoned researchers seem to have forgotten the Paracelsus Paradox.
