NMR analyses on the interactions of the yeast Tim50 C-terminal region with the presequence and Tim50 core domain

AbstractThe mitochondrial targeting signal in the presequence of mitochondrial precursor proteins is recognized by Tom20 and subsequently by Tim50 in mitochondria. Yeast Tim50 contains two presequence binding sites in the conserved core domain and in the fungi-specific C-terminal presequence binding domain (PBD). We report the NMR analyses on interactions of a shorter variant of PBD (sPBD), a shorter variant of PBD, with presequences. The presequence is recognized by sPBD in a similar manner to Tom20. sPBD can also bind to the core domain of Tim50 through the presequence binding region, which could promote transfer of the presequence from sPBD to the core domain in Tim50

A new antibacterial pyridinoside from a Streptomyces species

A new compound, 8-propionate-2-β-(D+)-glucosyl-9,10-pyranopyridine, was isolated from the chloroform extract of a Streptomyces species. The structure of the compound was confirmed by spectroscopic techniques including UV, IR, HR-ESI-MS, 1H-NMR, 13C-NMR, 1H-1H COSY and HMBC (long range coupling) spectra. The compound showed significant antibacterial activity against Gram-positive bacteria. The minimum inhibitory concentrations (MIC) of the isolated compound against Bacillus megaterium, Streptococcus β-haemolyticus, Bacillus subtilis, Escherichia coli, Salmonella typhi and Shigella dysenteriae were found to be 0.16, 0.08, 0.08, 0.04, 0.08 and 0.08 μM, respectively.Colegio de Farmacéuticos de la Provincia de Buenos Aire

PATTERNS OF PRESCRIPTION AND ANTIBIOTIC USE AMONG OUTPATIENTS IN A TERTIARY CARE TEACHING HOSPITAL OF BANGLADESH

Objective: Irrational drug use increased the risk of adverse drug reactions (ADRs), the emergence of drug resistance and a leading cause of morbidity and mortality worldwide. The study was designed to analyse prescription patterns and antibiotic use among outpatients in a tertiary care teaching hospital in Bangladesh.Methods: This prospective survey was conducted among the out-patients in a district hospital. The prescribed drugs were classified according to Anatomical and Therapeutic Chemical (ATC) classification system. Patient characteristics and drug data were recorded. The prescription pattern was analysed using general drug use indicators according to world health organisation (WHO).Results: A total of 405 prescriptions were analyzed of which 54% of child and 46% of adult prescriptions. The age and body weight of the patients were not mentioned in 30% of child and 62% of adult prescriptions and none of the prescriptions included sex of the patients. Physician's handwriting was not clear and legible in 31% prescriptions. A total 1362 drugs were used in this study with an average 3.36 drugs per prescription. However, none of the drugs was prescribed in generic name. Children were highly exposed to antibiotics (66%) than to adults (44%) of which cephalosporin's (30%) and macrolides (14%) were commonly used. Interestingly, non-steroidal anti-inflammatory drugs (NSAIDs) were also highly accounted in children (53%) than to adults (36%).Conclusion: Our results suggested that the prescription information was incomplete and physicians did not follow the standard guideline for drug treatment resulting in polypharmacy and indiscriminate use of antimicrobials irrespective to the age of patients

Physicochemical reports of gliclazide-carplex solid dispersions and tablets prepared with directly compressible co-processed excipients

Objectives: The main goal of this research was to develop better tablet formulations by utilizing solid dispersions (SDs) and coprocessing excipients composite to achieve a better release rate of poor water-soluble gliclazide. Methods: The solvent evaporation method made SDs of gliclazide with different carriers carplex 67, carplex 80, and carplex FPS 500 (weight ratio, 1:1). The drug release patterns of the SDs were all evaluated and optimized. The SDs were illustrated by using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Tablet batches FGC-1 to 8 were made using gliclazide-carplex 67 solid dispersions (GC67-SDs) and the co-processed composite of excipients, namely starch-MCC-povidone (SMP) and lactose-MCC-povidone-sodium starch glycolate (LMPS), prepared with coprocessing technology. We evaluated these batches by conducting physicochemical tests and comparing them to the existing commercial brand. Results: In a water medium, the release of gliclazide from SDs peaked within the first 30 min, showing a roughly 5∼6-fold increase compared to plain gliclazide. This quick dissolution rate may be due to the amorphization of the drug, which improved the specific surface area, and increased wettability caused by the hydrophilic properties of carplex particles. This has been confirmed through SEM, DSC, FTIR, and PXRD analysis. All FGC formulations had satisfactory pre-compression factor results, while the post-compression parameters indicated good mechanical strength and homogeneity across the blend. All produced tablets met the weight variation, friability, and disintegration time limit set by the compendia. Through in vitro drug release testing, it was discovered that all FGC tablet batches had consistent and nearly identical release results compared to SDs of gliclazide. However, the FGC-5 to 8 batches containing LMPS composites were determined to be the most effective formulations. In the first 30 min in a water medium, the percentage of drug generated from the FGC-8 tablets involving GC67-SDs and co-processed composite LMPS-4 is approximately 3.5 times higher than the average release of currently marketed products (MPs). After storing the selected FGC tablet batches for three months at 40 °C and 75 % RH, there were no noticeable alterations in the amount of drug and drug release profiles across the batches. Conclusion: Based on these findings, it appears that using the carplex silica-based SDs approach, along with gliclazide and co-processing excipients composite, could result in significant benefits compared to the current commercial brands. This approach could be effectively utilized to create solid dosage forms for drugs that have low solubility in water