Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients without co-infection

OBJECTIVE: An increased prevalence of type 2 diabetes mellitus (DM) has been associated with HCV in the non-HIV infected populations. To describe a similar association among HIV subjects, and explore the biological mechanisms. METHODS: In a cross-sectional analysis, we compared the prevalence of DM (using American Diabetes Association criteria) and insulin resistance (HOMA IR) and dyslipidemia among ARV naive patients with HIV and HIV/HCV infected patients enrolled in CPCRA FIRST (058) and the Metabolic Substudy (061). RESULTS: Among 1389 enrolled in the FIRST study and had HCV serology, the prevalence of diabetes was higher (5.9%) among HCV/HIV as compared to 3.3% among those with HIV alone (p=0.04). Among 417 enrolled in the metabolic substudy, 88 (21%) had HIV/HCV co-infection. As in the main study, the prevalence of DM was higher in HIV/HCV group (9 vs. 3%, p=0.03). The HIV/HCV infected were significantly older (43 vs. 37 years), non-white (83 vs. 70%), with a history of IDU (55 vs. 3%), had higher AST (61 vs. 39 U/l), ALT (55 vs. 43 U/l,) and lower cholesterol levels (3.97 vs. 4.25 mmol/l). By multivariate analysis among subjects <50 years, association between HCV and diabetes remained significant after adjusting for BMI, family history of diabetes (OR=3.7, 95% CI: 1.3-11.1, p=0.02). The insulin resistance (HOMA IR) was not different between the two groups, however, the prevalence of dyslipidemia was lower among HCV co-infected subjects. CONCLUSIONS: Subjects with HIV/HCV co-infection have a higher prevalence of diabetes and thus may need to be screened for it prior to initiation of anti-retroviral therapy, particularly if it is a PI based regimen.     

Formulation and Evaluation of Tramadol hydrochloride Rectal Suppositories

Rectal suppositories of tramadol hydrochloride were prepared using different bases and polymers like PEG, cocoa butter, agar and the effect of different additives on in vitro release of tramadol hydrochloride was studied. The agar-based suppositories were non-disintegrating/non-dissolving, whereas PEGs were disintegrating/dissolving and cocoa butter were melting suppositories. All the prepared suppositories were evaluated for various physical parameters like weight variation, drug content and hardness. The PEG and cocoa butter suppositories were evaluated for macromelting range, disintegration and liquefaction time. In vitro release study was performed by USP type I apparatus. The prepared suppositories were within the permissible range of all physical parameters. In vitro drug release was in the order of PEG>Agar>cocoa butter. Addition of PVP, HPMC in agar suppositories retards the release. The mechanism of drug release was diffusion controlled and follows first order kinetics. The results suggested that blends of PEG of low molecular weight (1000) with high molecular weight (4000 and 6000) in different percentage and agar in 10% w/w as base used to formulate rapid release suppositories. The sustained release suppositories can be prepared by addition of PVP, HPMC in agar-based suppositories and by use of cocoa butter as base.     

Migration responses of outer and inner meniscus cells to applied direct current electric fields

Injuries to the inner regions of the knee meniscus do not heal and can result in degenerative changes to the articular surface, ultimately leading to osteoarthritis. A possible stimulus to enhance meniscus healing is to use electric fields that induce galvanotaxis. In this study, a novel characterization of the effects of direct current electric fields on migration characteristics of meniscus cells was performed. Primary and passaged inner and outer meniscus cells were exposed to varying electric field strengths from 0 to 6 V/cm. Cell migration was tracked using time lapse digital photography, and cell displacement and cathodal direct velocity were quantified. Cytoskeletal staining was performed to examine actin distribution and nuclear content. Cell adhesion strength was quantified as a function of wall shear stress. Meniscus cells exhibited cathodal migration and cell elongation perpendicular to the applied electric field accompanied by actin reorganization. Outer meniscus cells migrated quicker and exhibited lower adhesion strengths when compared to inner meniscus cells. Passaged cells exhibited higher migration characteristics when compared to primary cells. Overall, this study demonstrated that electric fields can significantly enhance and direct meniscus cell migration and suggests the potential for their incorporation in strategies of meniscus repair and tissue engineering. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:103–111, 2012     

Cytologic detection of Trichomonas esophagitis in a patient with acquired immunodeficiency syndrome

Trichomonads are pathogens of the female genital tract and colonizers of the oropharynx. Gastrointestinal and pulmonary diseases have been reported in association with Trichomonas species, but a direct pathogenic effect of this organism in these organ systems remains controversial. Esophageal disease due to trichomonads has not been previously reported. A 43-yr-old man with acquired immunodeficiency syndrome (AIDS) with odynophagia and esophageal erosions was evaluated by endoscopy. Cytologic brushings from three of four sites in the esophagus were positive for trichomonads. Treatment with metronidazole resulted in clearance of the organism from the esophagus and improvement in clinical symptoms. We report esophageal trichomoniasis diagnosed on esophageal brush cytology in a man with AIDS. Clinical response was confirmed by cytologic studies and odynophagia improved with metronidazole treatment. Study of cytologic preparations was superior to biopsy for identification of this organism and was particularly useful in following the post-treatment course of disease. Diagn. Cytopathol. 1998;19:313–316. © 1998 Wiley-Liss, Inc.     

Krüppel-like factor 4 regulates macrophage polarization

Current paradigms suggest that two macrophage subsets, termed M1 and M2, are involved in inflammation and host defense. While the distinct functions of M1 and M2 macrophages have been intensively studied - the former are considered proinflammatory and the latter antiinflammatory - the determinants of their speciation are incompletely understood. Here we report our studies that identify Krüppel-like factor 4 (KLF4) as a critical regulator of macrophage polarization. Macrophage KLF4 expression was robustly induced in M2 macrophages and strongly reduced in M1 macrophages, observations that were recapitulated in human inflammatory paradigms in vivo. Mechanistically, KLF4 was found to cooperate with Stat6 to induce an M2 genetic program and inhibit M1 targets via sequestration of coactivators required for NF-κB activation. KLF4-deficient macrophages demonstrated increased proinflammatory gene expression, enhanced bactericidal activity, and altered metabolism. Furthermore, mice bearing myeloid-specific deletion of KLF4 exhibited delayed wound healing and were predisposed to developing diet-induced obesity, glucose intolerance, and insulin resistance. Collectively, these data identify KLF4 as what we believe to be a novel regulator of macrophage polarization.     

Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice

OBJECTIVES: Dyslipidemia associated with antiretroviral therapy is a common clinical problem among HIV-infected patients. Considering that the challenge of adherence to drugs (both antiretroviral and lipid lowering) may be substantial in routine HIV care, our objective was to evaluate the lipid-lowering effects of statins and fibrates in the management of HIV dyslipidemias in clinical practice setting. METHODS: Retrospective review of 103 ethnically diverse dyslipidemic HIV patients on antiretroviral therapy treated with lipid-lowering drugs (using National Cholesterol Education and Prevention II [NCEP II] guidelines) who were followed for a median of 70 weeks. RESULTS: An overall mean reduction of 16% in total cholesterol, 20% non-HDL cholesterol, and 18% in triglycerides was noted. There were no significant changes in HDL levels. On evaluation of the different drug classes, the mean (median) change in total cholesterol, were -9 (-7)% with fibrates, -11 (-14)% with statins and -23 (-22)% for dual therapy with fibrates and statins. The triglycerides decreased by -11 (-40)% in those treated with fibrates; -1 (-21)% in those with statins alone, and -32 (-42)% in those with dual therapy. Overall less than a fifth of patients reached the defined NCEP target goal reduction. On logistic regression analysis, only stopping protease inhibitors/ritonavir was independently associated with significant cholesterol reduction (OR: 10.14; 95% CI: 2.1-48.9; p < 0.005). CONCLUSION: In a primary care setting, the use of statins and/or fibrates may add to the complexity of HIV care, with only modest lipid lowering effects.