Current opinion in investigational drugs最新文献_第6页

Antimicrobial peptides for leishmaniasis. 利什曼病抗菌肽。

Current opinion in investigational drugs Pub Date : 2010-08-01

Steven L Cobb, Paul W Denny

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Cyclophilin inhibitors for the treatment of HCV infection. 治疗HCV感染的亲环蛋白抑制剂。

Current opinion in investigational drugs Pub Date : 2010-08-01

Gunter Fischer, Philippe Gallay, Sam Hopkins

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Cholera toxin B subunit modulation of mucosal vaccines for infectious and autoimmune diseases. 霍乱毒素B亚基对传染性和自身免疫性疾病粘膜疫苗的调节作用。

Current opinion in investigational drugs Pub Date : 2010-08-01

William Langridge, Béla Dénes, István Fodor

{"title":"Cholera toxin B subunit modulation of mucosal vaccines for infectious and autoimmune diseases.","authors":"William Langridge, Béla Dénes, István Fodor","doi":"","DOIUrl":"","url":null,"abstract":"Parenteral vaccination is generally considered to be the most effective form of therapy for protection against infectious diseases. In recent years, vaccination at mucosal surfaces and combinatorial vaccination strategies that link immunostimulatory molecules to antigens have been developed to enhance vaccine efficacy. Prominent among immunological enhancement strategies are the bacterial A and B toxins, which include the cholera toxin (CT)A and CTB subunits. In contrast to the toxic CTA subunit, the non-toxic CTB subunit displays both carrier and immunostimulatory properties. When linked to pathogen antigens, CTB can impart immunostimulatory properties that are characteristic of the linked antigen. Vaccination strategies have also been broadened to include 'self' proteins applied for the immunological suppression of autoimmunity. When CTB is linked to an autoantigen, the outcome might be considered paradoxical. In type 1 diabetes, self proteins become strongly immunosuppressive, while cancer CTB-autoantigen fusion proteins may exert a strong inflammatory response. This review discusses the immunostimulatory and immunosuppressive roles played by the CTB subunit in vaccine protection and therapy against infectious and autoimmune diseases.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"919-28"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29197919","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}

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Brain dysfunction in the era of combination antiretroviral therapy: implications for the treatment of the aging population of HIV-infected individuals. 联合抗逆转录病毒治疗时代的脑功能障碍:对艾滋病毒感染者老年人群治疗的影响

Current opinion in investigational drugs Pub Date : 2010-08-01

Uraina S Clark, Ronald A Cohen

{"title":"Brain dysfunction in the era of combination antiretroviral therapy: implications for the treatment of the aging population of HIV-infected individuals.","authors":"Uraina S Clark, Ronald A Cohen","doi":"","DOIUrl":"","url":null,"abstract":"Improvements in the treatment of HIV infection and in the advancement of combination antiretroviral therapy (cART) have led to an increase in the number of individuals with HIV who are surviving to an older age. Preventing the development of neurocognitive abnormalities has become an increasingly important issue in this aging patient population, which is already at risk for cognitive impairment as a result of the neuropathological effects of HIV. cART has been critical in reducing the overall severity of HIV-associated neurocognitive disorders (HAND), but numerous challenges remain, as the prevalence of HAND continues to be high. There are several key areas in which treatment could be improved to reduce the incidence and severity of HAND. The use of well-tolerated cART medications that are able to penetrate the blood-brain barrier hold particular promise, as these agents may enable increased viral suppression in the parenchyma and may reduce neurocognitive dysfunction. In addition, the improved treatment of comorbid medical conditions that are common in patient populations with HIV (eg, HCV, liver failure and metabolic syndrome) is critical, as several of these conditions are known to have a significant effect on neural functions. Various research approaches indicate that the development of agents that control free radicals, neurotoxicity, proinflammatory processes and apoptosis may also have substantial potential in this field.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"884-900"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021717/pdf/nihms-578007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diamidines for human African trypanosomiasis. 非洲人类锥虫病的二胺类药物。

Current opinion in investigational drugs Pub Date : 2010-08-01

Mary F Paine, Michael Zhuo Wang, Claudia N Generaux, David W Boykin, W David Wilson, Harry P De Koning, Carol A Olson, Gabriele Pohlig, Christian Burri, Reto Brun, Grace A Murilla, John K Thuita, Michael P Barrett, Richard R Tidwell

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Outpatient parenteral antimicrobial therapy: Recent developments and future prospects. 门诊非肠外抗菌治疗:最新进展和未来展望。

Current opinion in investigational drugs Pub Date : 2010-08-01

M Estee Török, Ann L N Chapman, M P Albert Lessing, Frances Sanderson, R Andrew Seaton

{"title":"Outpatient parenteral antimicrobial therapy: Recent developments and future prospects.","authors":"M Estee Török, Ann L N Chapman, M P Albert Lessing, Frances Sanderson, R Andrew Seaton","doi":"","DOIUrl":"","url":null,"abstract":"Patients with serious infections requiring parenteral antimicrobial therapy are usually hospitalized for treatment. For certain conditions, however, administration of parenteral antibiotics outside the hospital setting may be safe, efficacious, convenient for patients and cost-beneficial. Outpatient parenteral antimicrobial therapy (OPAT) was developed in the US initially and its use has expanded globally during the past three decades. A wide variety of infections are amenable to treatment by OPAT. Once-daily agents such as ceftriaxone or teicoplanin and, more recently, antimicrobials such as ertapenem or daptomycin have been used for OPAT. The use of higher doses and less-frequent dosing of existing agents is being explored, and exciting new developments include the emergence of agents with broader-spectrum activity against drug-resistant organisms and the use of antifungal agents in the OPAT setting. Future prospects in OPAT include the use of more recently launched drugs such as telavancin, as well as drugs in development, including dalbavancin (Durata Therapeutics Inc) and omadacycline (PTK-0796; Novartis AG/PARATEK Pharmaceuticals Inc). This review outlines recent developments in, and future prospects for, the antimicrobial agents used in OPAT.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"929-39"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200697","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: 0

Optimal antiretroviral therapy: HIV-1 treatment strategies to avoid and overcome drug resistance. 最佳抗逆转录病毒疗法:HIV-1治疗策略，以避免和克服耐药性。

Current opinion in investigational drugs Pub Date : 2010-08-01

Philip M Grant, Andrew R Zolopa

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Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection. Cenicriviroc，一种口服活性CCR5拮抗剂，可能治疗HIV感染。

Current opinion in investigational drugs Pub Date : 2010-08-01

Olga M Klibanov, Shannon H Williams, Cameron A Iler

{"title":"Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection.","authors":"Olga M Klibanov, Shannon H Williams, Cameron A Iler","doi":"","DOIUrl":"","url":null,"abstract":"Treatment of HIV-1-infected individuals is often complicated by the development of antiretroviral resistance, and novel antiretroviral agents with unique mechanisms of action and resistance profiles are needed to address this issue. CCR5 inhibitors represent a new class of antiretroviral agents that block the CCR5 receptor and prevent HIV-1 recognition and entry into CD4+ macrophages and T-cells. Tobira Therapeutics Inc is developing cenicriviroc (TBR-652, formerly TAK-652), a potent inhibitor of CCR5-tropic HIV-1 replication. Cenicriviroc has good oral bioavailability, a long t1/2 that allows once-daily dosing, and has demonstrated excellent antiviral potency with minimal toxicity in in vitro studies and phase I clinical trials. Encouraging efficacy results have been reported from phase II clinical trials in patients with CCR5-tropic HIV-1. The drug is also an inhibitor of the CCR2 receptor, which is known to be associated with inflammatory-related disease states, leading to Tobira initiating a phase I clinical trial in patients with rheumatoid arthritis. Cenicriviroc is a promising CCR5 inhibitor with potentially important anti-inflammatory effects, and warrants further investigation.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"940-50"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200698","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: 0

Danoprevir, a small-molecule NS3/4A protease inhibitor for the potential oral treatment of HCV infection. Danoprevir是一种小分子NS3/4A蛋白酶抑制剂，可用于口服治疗HCV感染。

Current opinion in investigational drugs Pub Date : 2010-08-01

Melanie Deutsch, George V Papatheodoridis

{"title":"Danoprevir, a small-molecule NS3/4A protease inhibitor for the potential oral treatment of HCV infection.","authors":"Melanie Deutsch, George V Papatheodoridis","doi":"","DOIUrl":"","url":null,"abstract":"Danoprevir (ITMN-191; RG-7227), under development by InterMune Inc and Roche Holding AG, is a promising, potent NS3/4A protease inhibitor for the oral treatment of HCV infection. Preclinical data demonstrated that danoprevir binds with high affinity and dissociates slowly from the HCV NS3 protease, allowing high liver drug exposure with only modest plasma drug exposure. A phase Ib, 'IFN-free' clinical trial demonstrated that danoprevir, combined with the HCV polymerase inhibitor RG-7128 (Pharmasset Inc/Roche Holding AG), was effective in reducing HCV-RNA levels in a large proportion of treatment-naïve patients with HCV infection and in approximately half of previously non-responsive patients with HCV-1 infection, without resistance or safety concerns. In a phase IIb trial in treatment-naïve patients with HCV-1 infection, danoprevir plus pegylated IFNalpha2a and ribavirin resulted in undetectable levels of HCV-RNA in the majority of patients, without any evidence of viral resistance; however, the high-dose danoprevir arm was prematurely terminated because of grade 4 ALT elevations. Phase I trials have also demonstrated that ritonavir boosting improved the pharmacokinetic profile of danoprevir; therefore, at the time of publication, a phase IIb trial to evaluate ritonavir-boosted, low-dose danoprevir in combination with RG-7128 was planned.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"951-63"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200699","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}

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Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection. vec -4x是一种治疗性疫苗，由四种工程肽组成，具有治疗HIV感染的潜力。

Current opinion in investigational drugs Pub Date : 2010-08-01

Taff Jones

{"title":"Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection.","authors":"Taff Jones","doi":"","DOIUrl":"","url":null,"abstract":"Vacc-4x is being developed by Bionor Immuno AS as a therapeutic vaccine to be used in conjunction with antiretroviral therapies by individuals infected with HIV. The vaccine is comprised of four synthetic peptides describing sequences from within the highly conserved HIV core protein p24, which are thought to induce T-cell-mediated responses. Vacc-4x was assessed in 51 patients infected with HIV in one phase I and one phase II clinical trial and was demonstrated to be safe and generally well tolerated with no significant adverse events. Promisingly, the vaccine was reported to induce cell-mediated immunity, with a third of vaccinees eligible for follow-up remaining off antiretroviral therapy and being essentially symptom-free 4 years after treatment. Nonetheless, without the inclusion of a placebo group, the data will be looked upon with a degree of skepticism in the scientific community. A phase IIb, placebo-controlled clinical trial to address this issue is currently ongoing, with data expected to become available by the end of 2010. If Vacc-4x vaccinees demonstrate significantly better responses than the placebo group in this trial, the prospects for Vacc-4x could be highly promising.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"964-70"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200700","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: 0