Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

AIM: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. METHODS: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. RESULTS: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. CONCLUSION: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

Formation of ZnS quantum dots using green tea extract: applications to protein binding, bio-sensing, anti-bacterial and cell cytotoxicity studies.

Biocompatible quantum dots (QDs) have attracted a lot of attention due to their potential biological applications (drug delivery, sensing and diagnosis). Here, we have synthesized 2-4 nm sized biocompatible zinc sulphide (ZnS) QDs using a plant leaf extract as an immobilizing and stabilizing agent via a green route. We have investigated the biological effects of ZnS QDs in a variety of applications, including (1) anti-bacterial activity, (2) cell cytotoxicity, (3) bio-sensing and (4) protein binding. Studies on the anti-bacterial activity of the as-synthesized ZnS QDs against E. coli and E. faecalis inhibited bacterial growth effectively and showed a cytotoxic effect on the HeLa cell line. The biosynthesized ZnS QDs act as a fluorescence probe to detect bilirubin and rifampicin (RFP) with a wide linear range, high sensitivity, good selectivity, and a low limit of detection (LOD), with LOD values of 22.12 ± 0.25 ng mL-1 and 122.37 ± 0.42 ng mL-1, respectively. In a biological matrix, the QDs can form a complex with biomacromolecules; therefore, we studied the interaction between a carrier protein (HSA) and the as-synthesized ZnS QDs. The surface functionalized and nano-sized ZnS-GT QDs were observed to form complexes with the human serum albumin (HSA) protein and quenched the intrinsic fluorescence of HSA through static and dynamic quenching modes. The binding affinity was observed to be of the order of 105 M-1 for the HSA-ZnS-GT QD interactions, which can be considered as a reversible mode of binding. The effect of the ZnS QDs on other ligands and protein interactions was also studied. Enhanced binding affinities for HSA-quercetin ((5.994 ± 0.139) × 105 M-1) and HSA-luteolin ((3.068 ± 0.127) × 105 M-1) interactions were also observed in the presence of ZnS-GT QDs.

Complexation of turmeric and curcumin mediated silver nanoparticles with human serum albumin: Further investigation into the protein-corona formation, anti-bacterial effects and cell cytotoxicity studies.

Biosynthesized noble metal nanoparticles have been of recent interest due to their broad implications in the future biomedicinal field. We have synthesized silver nanoparticle using turmeric-extract and its major component curcumin as reducing and stabilizing agents. Further, we have investigated the protein-NPs interaction focusing the inspection of the role of biosynthesized AgNPs on any conformational changes of the protein, binding and thermodynamic parameters using spectroscopic techniques. Fluorescence quenching studies revealed that both CUR-AgNPs and TUR-AgNPs have moderate binding affinities (∼104 M-1) towards human serum albumin (HSA) and static quenching mechanism was involved in the binding. Estimated thermodynamic parameters indicate the involvement of hydrophobic forces in the binding processes. The surface charge potential of the biosynthesized AgNPs became more negative upon complexation with HSA as observed from Zeta potential measurements. Antibacterial efficacies of the biosynthesized AgNPs were evaluated against Escherichia coli (gram-negative) and Enterococcus faecalis (gram-positive) bacterial strains. The AgNPs were found to destroy the cancer (HeLa) cell lines in vitro. The overall findings of our study successfully outline the detailed insight of the protein corona formation by biocompatible AgNPs and their biological applications concerning the future scope in the biomedicinal field.

The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study.

PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.

A review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications.

Non-enzymatic reaction involving carbonyl of reducing sugars and amino groups in proteins produces advanced glycation end products (AGEs). AGE accumulation in vivo is a crucial factor in the progression of metabolic and pathophysiological mechanisms like obesity, diabetes, coronary artery disease, neurological disorders, and chronic renal failure. The body's own defense mechanism, synthetic inhibitors, and natural inhibitors can all help to prevent the glycation of proteins. Synthetic inhibitors have the potential to suppress the glycation of proteins through a variety of pathways. They could avoid Amadori product development by tampering with the addition of sugars to the proteins. Besides which, the free radical scavenging and blocking crosslink formation could be another mechanism behind their anti-glycation properties. In comparison with synthetic substances, naturally occurring plant products have been found to be comparatively non-toxic, cheap, and usable in an ingestible form. This review gives a brief introduction of the Maillard reaction; formation, characterization and pathology related to AGEs, potential therapeutic approaches against glycation, natural and synthetic inhibitors of glycation and their probable mechanism of action. The scientific community could get benefit from the combined knowledge about important molecules, which will further guide to the design and development of new pharmaceutical compounds.

An investigation into the altered binding mode of green tea polyphenols with human serum albumin on complexation with copper.

Green tea is rich in several polyphenols, such as (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). The biological importance of these polyphenols led us to study the major polyphenol EGCG with human serum albumin (HSA) in an earlier study. In this report, we have compared the binding of ECG, EGC, and EGCG and the Cu(II) complexes of EGCG and ECG with HSA. We observe that the gallate moiety of the polyphenols plays a crucial role in determining the mode of interaction with HSA. The binding constants obtained for the different systems are 5.86 ± 0.72 × 104 M⁻¹ (K ECG-HSA), 4.22 ± 0.15 × 104 M⁻¹ (K ECG-Cu(II)-HSA), and 9.51 ± 0.31 × 104 M⁻¹ (K EGCG-Cu(II)-HSA) at 293 K. Thermodynamic parameters thus obtained suggest that apart from an initial hydrophobic association, van der Waals interactions and hydrogen bonding are the major interactions which held together the polyphenols and HSA. However, thermodynamic parameters obtained from the interactions of the copper complexes with HSA are indicative of the involvement of the hydrophobic forces. Circular dichroism and the Fourier transform infrared spectroscopic measurements reveal changes in α-helical content of HSA after binding with the ligands. Data obtained by fluorescence spectroscopy, displacement experiments along with the docking studies suggested that the ligands bind to the residues located in site 1 (subdomains IIA), whereas EGC, that lacks the gallate moiety, binds to the other hydrophobic site 2 (subdomain IIIA) of the protein.