Current drug targets. Immune, endocrine and metabolic disorders最新文献_第3页

Water transport into bile and role in bile formation. 水进入胆汁和在胆汁形成中的作用。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064850

Giuseppe Calamita, Domenico Ferri, Patrizia Gena, Giuseppa E Liquori, Raúl A Marinelli, Giuliano Meyer, Piero Portincasa, Maria Svelto

引用次数: 0

The genetic background of cholesterol gallstone formation: an inventory of human lithogenic genes. 胆固醇胆石形成的遗传背景:人类产石基因的清单。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064841

Frank Lammert, Siegfried Matern

引用次数: 35

Pharmacological manipulation of biliary water and lipids: potential consequences for prevention of acute biliary pancreatitis. 胆道水和脂质的药理学操作:预防急性胆道性胰腺炎的潜在后果。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064814

Niels G Venneman, Gerard P vanBerge-Henegouwen, Karel J van Erpecum

{"title":"Pharmacological manipulation of biliary water and lipids: potential consequences for prevention of acute biliary pancreatitis.","authors":"Niels G Venneman, Gerard P vanBerge-Henegouwen, Karel J van Erpecum","doi":"10.2174/1568008054064814","DOIUrl":"https://doi.org/10.2174/1568008054064814","url":null,"abstract":"Acute biliary pancreatitis, caused by macroscopic cholesterol gallstones or microlithiasis, is often a severe disease with considerable morbidity and mortality. Formation of cholesterol gallstones and microlithiasis is caused by cholesterol crystallization from cholesterol supersaturated gallbladder bile. Particularly patients with fast and extensive crystallization, due to highly concentrated bile, low biliary phospholipid contents and gallbladder mucin hypersecretion seem at risk for pancreatitis. Patients who suffered from acute biliary pancreatitis should undergo cholecystectomy as secondary prevention strategy. For patients at high surgical risk, endoscopic sphincterotomy may be an appropriate alternative. Pharmacological manipulation of biliary lipids by the hydrophilic bile salt ursodeoxycholic acid is reserved for patients with recurrent pancreatitis despite previous cholecystectomy or sphincterotomy, or with contraindications to surgical and endoscopic treatment. Maintenance therapy with ursodeoxycholic acid is however a very effective secondary prevention strategy. Potentially, secondary prevention of acute biliary pancreatitis could also be achieved through decreasing biliary mucin contents by UDCA, NSAIDs or N-acetylcystein, or through achieving bile dilution (currently not feasible).","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"193-8"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24947822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Therapeutic targets for the prevention of type 1 diabetes mellitus. 预防1型糖尿病的治疗靶点。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064823

N Singh, J P Palmer

{"title":"Therapeutic targets for the prevention of type 1 diabetes mellitus.","authors":"N Singh, J P Palmer","doi":"10.2174/1568008054064823","DOIUrl":"https://doi.org/10.2174/1568008054064823","url":null,"abstract":"The pathogenesis of type 1 diabetes is multifactorial, involving genetic susceptibility, autoimmune mechanisms, and environmental factors. This article will focus on two main strategies for altering the underlying disease process in type 1 diabetes. The first strategy is to identify individuals at risk for the development of diabetes and to halt the immune process before it leads to overt clinical disease, Promising in vitro and animal studies with nicotinamide, parenteral insulin, and oral insulin led to large clinical prevention studies, such as the European Nicotinamide Diabetes Intervention Trial and the Diabetes Prevention Trial (DPT-1). These studies failed to show that nicotinamide and insulin prevented the disease in at risk relatives of patients with type 1 diabetes and left many questions unanswered. The second strategy focuses on intervention shortly after diagnosis in order to arrest the destruction of beta cells and to preserve residual beta-cell function as long as possible. Cyclosporin was an effective immunosuppressive but was rejected as a potential treatment for type 1 diabetes because of its renal toxicity. Recently, more attention has been focused on an anti-CD3 antibody, on DiaPep277, and on glutamic acid decarboxylase (GAD). Animal studies and small short-term human trials with these compounds have suggested that they may be effective interventions in patients recently diagnosed with type 1 diabetes.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"227-36"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24947827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Ion transport across the gallbladder epithelium. 离子在胆囊上皮上的转运。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064805

G Meyer, F Guizzardi, S Rodighiero, R Manfredi, S Saino, C Sironi, M L Garavaglia, C Bazzini, G Bottà, P Portincasa, G Calamita, M Paulmichl

{"title":"Ion transport across the gallbladder epithelium.","authors":"G Meyer, F Guizzardi, S Rodighiero, R Manfredi, S Saino, C Sironi, M L Garavaglia, C Bazzini, G Bottà, P Portincasa, G Calamita, M Paulmichl","doi":"10.2174/1568008054064805","DOIUrl":"https://doi.org/10.2174/1568008054064805","url":null,"abstract":"The function of the gallbladder is not only to store bile, but also to concentrate it during the interdigestive phase by means of salt-dependent water reabsorption. On the contrary, secretions of water and salt take place during the digestive phase. Dysregulation of ion absorption or secretion are common in many gallbladder diseases, such as colelithiasis. Transepithelial absorptions are determined by the Na+/K+ pump on the basolateral membrane, and by several apical membrane Na(+)-coupled transporters. Among these, some isoforms of Na+/H+ and Cl-/HCO3(-) exchangers have been studied. The presence of a Na(+)-Cl(-) simport has been molecularly and functionally characterized in some animal species. The ion transepithelial secretion is mainly dependent on an apical chloride transport attributable to a CFTR-like cAMP-activated channel with high permeability to HCO3(-). The apical membrane electrical potential is one of the factors influencing anion secretion and is maintained by the activity of cAMP-dependent K+ channels. The regulation of the activity of these channels is complex, because of their sensitivity to voltage, and to intracellular calcium and pH. The coordinated interplay underlying the regulation of transporters and channels needs to be clarified yet, as well as the interactions between transporters, channels and aquaporins.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"143-51"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25238805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Myocardial insulin resistance and cardiac complications of diabetes. 心肌胰岛素抵抗与糖尿病心脏并发症。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064869

E Dale Abel

{"title":"Myocardial insulin resistance and cardiac complications of diabetes.","authors":"E Dale Abel","doi":"10.2174/1568008054064869","DOIUrl":"https://doi.org/10.2174/1568008054064869","url":null,"abstract":"Cardiovascular disease is a major cause of mortality and morbidity in individuals with obesity, type 2 diabetes and the metabolic syndrome. The mechanisms for this are partially understood, but include increased atherosclerosis, hypercoagulability and increased hypertension. Epidemiological data suggests however, that a component of the excess cardiovascular mortality occurs independently of underlying coronary artery disease. Indeed, diabetes is an independent risk factor for the development of heart failure and the mechanisms responsible remain to be clarified. Insulin resistance in skeletal muscle, adipose tissue and the liver are widely recognized features of obesity and type 2 diabetes, and contribute to the pathogenesis of impaired glucose homeostasis. Insulin resistance has also been described in the vasculature, and may contribute to endothelial dysfunction and atherosclerosis. The heart is an insulin responsive organ and less is known about whether or not the heart becomes insulin resistant in diabetes and what the pathogenic consequences of this might be. This review will discuss the currently available evidence from human and animal studies, that the heart may become insulin resistant in obesity and type 2 diabetes. The potential consequences of this on cardiac structure, function and metabolism will be discussed as well as recent data from transgenic mice with perturbed cardiac insulin sensitivity that have shed interesting new insight into potential mechanisms linking cardiac insulin resistance with myocardial dysfunction in diabetes.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"219-26"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24947826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 86

Contribution of canalicular glutathione efflux to bile formation. From cholestasis associated alterations to pharmacological intervention to modify bile flow. 小管谷胱甘肽外排对胆汁形成的贡献。从胆汁淤积相关的改变到改变胆汁流动的药物干预。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064931

Ignazio Grattagliano, Piero Portincasa, Vincenzo O Palmieri, Giuseppe Palasciano

{"title":"Contribution of canalicular glutathione efflux to bile formation. From cholestasis associated alterations to pharmacological intervention to modify bile flow.","authors":"Ignazio Grattagliano, Piero Portincasa, Vincenzo O Palmieri, Giuseppe Palasciano","doi":"10.2174/1568008054064931","DOIUrl":"https://doi.org/10.2174/1568008054064931","url":null,"abstract":"At least one third of the bile flow is driven osmotically by the amount of hepatic glutathione excreted into canalicular spaces. Beyond the importance of this secretory mechanism for bile formation, the excretion of glutathione is an important way to discharge toxic anionic compounds deriving from liver metabolism of exogenous and endogenous substances. Thus, biliary secretion of glutathione and its conjugates really works as a major detoxification system for the hepatocytes. Derangement of hepatic and/or biliary glutathione status can occur in several experimental animal models of liver injury and in human diseases. In the present review, we will focus on mechanisms of bile glutathione efflux and changes associated with cholestatic conditions. Novel findings on the role of water channels and of the multidrug resistant proteins in bile salt-independent bile formation, will also be discussed. New routes of intervention to modify bile flow for therapeutic purposes are considered.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"153-61"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25238806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Effects of fatty acid bile acid conjugates (FABACs) on biliary lithogenesis: potential consequences for non-surgical treatment of gallstones. 脂肪酸-胆汁酸缀合物(FABACs)对胆道结石形成的影响:胆结石非手术治疗的潜在后果。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064904

Fred M Konikoff, Tuvia Gilat

{"title":"Effects of fatty acid bile acid conjugates (FABACs) on biliary lithogenesis: potential consequences for non-surgical treatment of gallstones.","authors":"Fred M Konikoff, Tuvia Gilat","doi":"10.2174/1568008054064904","DOIUrl":"https://doi.org/10.2174/1568008054064904","url":null,"abstract":"Fatty acid bile acid conjugates (FABACs) are novel synthetic lipid molecules, which were designed for the treatment of cholesterol gallstones. The rationale was to combine a cholesterol solubilizing moiety (a saturated fatty acid) with a bile acid (cholic acid) as a vehicle to enable secretion into bile and entry into the enterohepatic circulation. An amide bond was used to provide stability against intestinal degradation. Initial in vitro studies showed that FABACs are indeed cholesterol solubilizers, able to prevent biliary cholesterol crystallization. Arachidyl-amido-cholanoic acid (Aramchol) was found to be the most potent FABAC in these studies. Animal studies revealed that Aramchol was absorbed after oral administration and could prevent cholesterol crystallization as well as dissolve preformed crystals in rodents fed a lithogenic diet. In gallstone susceptible mice, Aramchol prevented gallstone formation and dissolved gallstones. FABACs were found to be metabolically active substances, also able to decrease blood cholesterol, atherosclerotic plaques and fat accumulation in the liver in several animal species. The underlying mechanisms of action are under active investigation, and several effects, e.g. on cholesterol and bile salt metabolizing enzymes as well as cholesterol efflux from cells have been discovered. These findings are, however, only the beginning of our understanding of the metabolic actions as well as the potential of use of FABACs as therapeutic agents.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"171-5"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25238808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Drugs affecting biliary lipid secretion and gallbladder motility: their potential role in gallstone treatment and prevention. 影响胆脂分泌和胆囊运动的药物:在胆结石治疗和预防中的潜在作用。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064940

Gerard P vanBerge-Henegouwen, Niels G Venneman, Karel J van Erpecum, Piero Portincasa

{"title":"Drugs affecting biliary lipid secretion and gallbladder motility: their potential role in gallstone treatment and prevention.","authors":"Gerard P vanBerge-Henegouwen, Niels G Venneman, Karel J van Erpecum, Piero Portincasa","doi":"10.2174/1568008054064940","DOIUrl":"https://doi.org/10.2174/1568008054064940","url":null,"abstract":"Gallstone disease in the Western world has an estimated prevalence of 10-15% and more than 75% are cholesterol-enriched gallstones. Defective gallbladder motility has been identified as an important pathogenic factor for cholesterol gallstone disease. Various agents may enhance or impair postprandial gallbladder motility, and their effects on interdigestive gallbladder and intestinal motility should also be taken into account. Patients in high-risk situations for gallstone disease, and those chronically treated with drugs inhibiting gallbladder motility (e.g. somatostatin analogues) may benefit from improving gallbladder motility with prokinetic agents. Whether such a strategy can really prevent gallstone formation is still unknown, long-term studies are lacking so far. The efficacy of bile acid therapy with UDCA for gallstone dissolution or for prevention in high risk patients is limited and hampered by high recurrence rates. The efficacy of UDCA in prevention of colics or gallstone related complications in symptomatic patients with gallbladder stones with contraindications for operation or on the waiting list should be explored further, since several retrospective studies showed favourable outcomes with this strategy.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"5 2","pages":"185-91"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008054064940","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25238810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Lipid transport into bile and role in bile formation. 脂质转运到胆汁和在胆汁形成中的作用。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2005-06-01 DOI: 10.2174/1568008054064887

Albert K Groen, Ronald P J Oude Elferink

引用次数: 5