Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: a cross-sectional study

Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A- controls with an eGFR > 60 ml/min per 1.73 m2, Group B - controls with an eGFR < 60 ml/min per 1.73 m2, Group C- T2DM subjects with an eGFR > 60 ml/min per 1.73 m2, and Group D - T2DM subjects with an eGFR < 60 ml/ min per 1.73 m2. In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m2 than in subjects with an eGFR > 60 ml/min per 1.73 m2. However, the difference was only significant between the control groups (p < 0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p < 0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.     

HIV Prevalence,Risk Behavior,Hormone Use and Surgical History Among Transgender Persons in Thailand

While Male-to-female transgender persons (TG) are believed to often engage in sex work and have high HIV infection risk, little is known about demographics, surgical and hormone use history, risk behaviors and HIV prevalence. Between March and October 2005, 474 TG from Bangkok, Chiangmai, and Phuket were surveyed using venue-day-time sampling. Of 474 participants, overall HIV prevalence was 13.5%. Most participants had completed at least secondary or vocational education (79.2%), gender self-identified as female (89.0%), had received money, gifts or valuables for sex (60.8%), and reported hormone use (88.6%). Surgical history was taken from 325 participants. Of these, 68.6% reported some form of surgery and 11.1% had undergone penile-vaginal reconstructive surgery. In multivariate analysis, being recruited from a park/street; older age, anal sex role identification as “versatile” and anal sex debut before age 13 were independently associated with HIV prevalence. The development, implementation and evaluation of culturally appropriate sexual health interventions for Thai TG is urgently needed.     

Alkyl-substituted polyaminohydroxamic acids: a novel class of targeted histone deacetylase inhibitors

The reversible acetylation of histones is critical for regulation of eukaryotic gene expression. The histone deacetylase inhibitors trichostatin (TSA, 1), MS-275 (2) and suberoylanilide hydroxamic acid (SAHA, 3) arrest growth in transformed cells and in human tumor xenografts. However, 1-3 suffer from lack of specificity among the various HDAC isoforms, prompting us to design and synthesize polyaminohydroxamic acid (PAHA) derivatives 6-21. We felt that PAHAs would be selectively directed to chromatin and associated histones by the positively charged polyamine side chain. At 1 microM, compounds 12, 15 and 20 inhibited HDAC by 74.86, 59.99 and 73.85%, respectively. Although 20 was a less potent HDAC inhibitor than 1, it was more potent than 2, more effective as an initiator of histone hyperacetylation, and significantly more effective than 2 at re-expressing p21Waf1 in ML-1 leukemia cells. On the basis of these results, PAHAs 6-21 represent an important new chemical class of HDAC inhibitors.     

Peroral delivery of insulin using chitosan derivatives: a comparative study of polyelectrolyte nanocomplexes and nanoparticles

Polymeric delivery systems based on nanoparticles (NP) have emerged as a promising approach for peroral insulin delivery. Using a trimethyl chitosan (TMC) and a PEG-graft-TMC copolymer, polyelectrolyte complexes (PEC) and nanoparticles were prepared and their properties were compared. The amount of insulin was quantified by HPLC and the stability of PEC and NP upon exposure to simulated gastrointestinal (GI) fluid was monitored by dynamic laser light scattering. It was shown that polymer/insulin (+/-) charge ratio played an important role in PEC and NP formation. Stable, uniform, and spherical PEC/NP with high insulin association efficiency (AE) were formed at or close to optimized polymer/insulin (+/-) charge ratio, depending on polymer structure. All PEC were more stable in pH 6.8 simulated intestinal fluid (SIF) than NP. The PEC also appeared to play some role in protecting insulin from degradation at higher temperature and with proteolytic enzyme more efficiently than NP. On the basis of these results, polyelectrolyte complexation can be suggested as a potentially useful technique for generating insulin delivery systems for peroral administration.