Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes.

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.

Emerging Trends in Non-Interferon-Based Genotype-Specific Antiviral Agents: Pharmaceutical Perspectives.

Hepatitis C virus (HCV) presents a serious global health threat. Initially, the health-care community mainly focused on interferon (IFN)-based therapeutic options to eradicate HCV, but with the passage of time, these applications became unsuitable due to some serious side effects related to the use of IFN. In recent years, research conducted on different phases of HCV's life cycle has opened a new gateway for the use of a direct-acting new generation of anti-HCV agents. Their safer and ultrarapid response has made possible the introduction of triple therapy and use of IFN-free therapeutic treatment strategies. However, the high cost of these successful therapies has raised serious concerns, particularly in low-income countries, and this has forced pharmaceutical scientists to explore more cost-effective IFN-free alternatives for the treatment of HCV. In this article, we have briefly summarized the latest data regarding the research and development of non-IFN-based antiviral agents. The studies mentioned in this article highlight the significance of non-IFN-based direct-acting antiviral (DAA) agents. Economical alternative anti-HCV agents are expected to become available in the near future for better and more cost-effective treatments of HCV.

Assessment of release kinetics, stability and polymer interaction of poloxamer 407-based thermosensitive gel of interleukin-1 receptor antagonist.

Sustained delivery of proteins from polymer-based thermosensitive gel has achieved considerable attention since last decade. In our previous work, we developed a formulation for sustained delivery of IL-1Ra-loaded poloxamer 407 formulation and investigated its in vitro and in vivo characteristics. In the present work, we extended this approach to investigate stability of IL-1Ra from poloxamer 407 formulation stored at 4 °C, 25 °C and 40 °C for 3 months. Samples were taken and in vitro drug release kinetics was studied. Percent of drug content was measured using the BCA method. DSC and SDS-PAGE were used to assess the conformational stability of IL-1Ra. FTIR spectroscopy was performed to investigate the drug-polymer interaction. From the results, it was found that gelation temperature, viscosity and in vitro release pattern of IL-1Ra from poloxamer 407 formulation at 4 °C were almost same throughout the stability study period. DSC profiles of IL-1Ra loaded in poloxamer 407 formulation increased the thermostability of IL-1Ra significantly in poloxamer 407 formulation. There were no apparent changes in the entire FTIR spectrum of the IL-1Ra that would suggest that there was no effect of the polymer on the structure of IL-1Ra. Moreover, results of SDS-PAGE confirmed the stability of IL-1Ra in poloxamer 407 formulation. These results provided evidence that poloxamer 407 is a promising polymer not only for sustained delivery of IL-1Ra but also provides conformational stability for extended time.