HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF GLIMEPIRIDE AND TIMOLOL IN PHARMACEUTICAL FORMULATIONS USING BRITTON -ROBINSON BUFFER IN MOBILE PHASES

Actually, Glimepiride (GLI) and Timolol (TIM) are analysed by several analytical techniques such as HPLC, Uv Vis and electrochemical methods, but in this study these compounds were determined by use Britton-Robinson (B-R) buffer pH3 in mobile phases as a new work. B-R pH3 : Acetonitrile : Water : Methanol (10 : 30 : 10 : 50 % v/v/v/v) and B-R pH3 : Acetonitrile : Methanol (30 : 15 : 55 % v/v/v), were used as mobile phases for chromatographic studies of GLI and TIM respectively. 1´10-3 mol L-1 of GLI and TIM were prepared  by dissolving the suitable weight of analyte in methanol and distilled water respectively, in 50 ml volumetric flask. GLI and TIM were HPLC separated from interferences and analytical determined using C-18 (5µm) with UV detector at 254 nm and 1.00 mL min-1 flow rate by 10 µL injection volume. The calibration curves for GLI and TIM  were studied over the range 1×10-4 to 1×10-3 mol L-1 (correlation coefficient = 0.994, n=6) for GLI and (correlation coefficient = 0.996, n=6) for TIM. The HPLC reproducibility and stability were evaluated for 5×10-4 mol L-1 of GLI and TIM , yielded good results for ten HPLC measurements with relative standard deviations RSD% were 0.43 and 1.1%, and good stability observed. The developed HPLC was applied to determine of GLI and TIM in pharmaceutical formulations with mean recoveries 103% ±0.71 and 99% ±1.0, respectively.  

Biosynthetic Manipulation of Tryptophan in Bacteria: Pathways and Mechanisms

Tryptophan, the most chemically complex and the least abundant of the 20 common proteinogenic amino acids, is a biosynthetic precursor to a large number of complex microbial natural products. Many of these molecules are promising scaffolds for drug discovery and development. The chemical features of tryptophan, including its ability to undergo enzymatic modifications at almost every atom in its structure and its propensity to undergo spontaneous, non-enzyme catalyzed chemistry, make it a unique biological precursor for the generation of chemical complexity. Here, we review the pathways that enable incorporation of tryptophan into complex metabolites in bacteria, with a focus on recently discovered, unusual metabolic transformations

Attenuation of the association between sugar-sweetened beverages and diabetes risk by adiposity adjustment: a secondary analysis of national health survey data

Purpose: While weight gain and obesity are the dominant factors, dietary sugar and specifically sugar-sweetened beverages (SSB) has been implicated in causing type 2 diabetes (T2DM). We assessed how much of the apparent effect of SSB is explained by adiposity, but not captured by adjustment for BMI, which is a poor index of body fat. Methods: We examined data from 5187 adults (mean age 50.8 years, SD = 16.4, 172 (3.3%) T2DM), from the Scottish Health Survey 2003 and 2008–2010 databases. Logistic regression was used to assess the association between SSB consumption and T2DM (non-insulin treated) and its attenuation (reduction in odds ratios, ORs), after entering published anthropometric indices of adiposity into the regression model, adjusted for age, sex, social class, education, smoking, alcohol consumption and physical activity. Results: Compared with low SSB categories (“less often/never”, once/week or 1–3 times/month), the OR without adiposity adjustment for having T2DM in high SSB consumers (2–3, 4–5, ≥ 6/day) was 2.56 (95% CI 1.12–5.83; p = 0.026). That OR was marginally changed by adjusting for BMI (+ 4.3%), WC (+ 5.5%) or total body fat (− 4.3%), but greatly attenuated by adjusting for estimated %body fat (− 23.4%). These indices had similar influences on the associations between SSB and T2DM combining known T2DM patients with unknown HbA1c > 6.5%, > 48 mmol/mol. Conclusions: Associations between SSB and T2DM are attenuated more markedly by adjustment with estimated %body fat than with BMI, indicating an adiposity effect not captured using BMI. Future research should employ best available estimates of adiposity

Alpha Lipoic Acid for Symptomatic Peripheral Neuropathy in Patients with Diabetes: A Meta-Analysis of Randomized Controlled Trials

Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. The databases MEDLINE and EMBASE were searched using the key words “lipoic acid”, “thioctic acid”, “diabet∗”, and the MeSH-terms “thioctic acid” and “diabetes mellitus”. Randomised controlled trials using the TSS score as the outcome measure were selected and assessed for their methodological quality. Study selection and quality assessment were performed independently by three observers. Results. Overall, the pooled standardized mean difference estimated from all trials revealed a reduction in TSS scores of −2.26 (CI: −3.12 to −1.41; P = 0.00001) in favour of alpha lipoic acid administration. Subgroup analyses of oral administration (−1.78 CI: −2.45 to −1.10; P = 0.00001) and intravenous administration (−2.81 CI: −4.16 to −1.46; P = 0.0001) confirmed the robustness of the overall result. Conclusions. When given intravenously at a dosage of 600 mg/day over a period of 3 weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). It is unclear if the significant improvements seen after 3–5 weeks of oral administration at a dosage of >600 mg/day are clinically relevant

Medical knowledge and clinical productivity:independently correlated metrics during radiology residency

OBJECTIVE: To determine the association between medical knowledge relevant to radiology practice (as measured by the Dutch radiology progress test [DRPT]) and clinical productivity during radiology residency. METHODS: This study analyzed the results of 6 DRPTs and time period–matched clinical production points of radiology residents affiliated to a tertiary care academic medical center between 2013 and 2016. The Spearman correlation analysis was performed to determine the association between DRPT percentile scores and average daily clinical production points. Linear regression analyses were performed to determine the association of DRPT percentile scores with average daily clinical production points, adjusted for age and gender of the radiology resident, and postgraduate year. RESULTS: Eighty-four DRPTs with time period–matched clinical production points were included. These 84 DRPTs were made by 29 radiology residents (18 males and 11 females) with a median age of 31 years (range: 26–38 years). The Spearman correlation coefficient between DRPT percentile scores and average daily clinical production points was 0.550 (95% confidence interval: 0.381–0.694) (p < 0.001), indicating a significant moderate positive association. On multivariate analysis, average daily clinical production points (β coefficient of 0.035, p = 0.003), female gender of the radiology resident (β coefficient of 12.690, p = 0.001), and postgraduate year (β coefficient of 10.179, p < 0.001) were significantly associated with DRPT percentile scores. These three independent variables achieved an adjusted R(2) of 0.527. CONCLUSION: Clinical productivity is independently associated with medical knowledge relevant to radiology practice during radiology residency. These findings indicate that clinical productivity of a resident could be a potentially relevant metric in a radiology training program. KEY POINTS: • There is a significant moderate correlation between medical knowledge relevant to radiology practice and clinical productivity during radiology residency. • Medical knowledge relevant to radiology practice remains independently associated with clinical productivity during radiology residency after adjustment for postgraduate year and gender. • Clinical productivity of a resident may be regarded as a potentially relevant metric in a radiology training program

An Algorithm: Optimal Homotopy Asymptotic Method for Solutions of Systems of Second-Order Boundary Value Problems

Optimal homotopy asymptotic method (OHAM) is proposed to solve linear and nonlinear systems of second-order boundary value problems. OHAM yields exact solutions in just single iteration depending upon the choice of selecting some part of or complete forcing function. Otherwise, it delivers numerical solutions in excellent agreement with exact solutions. Moreover, this procedure does not entail any discretization, linearization, or small perturbations and therefore reduces the computations a lot. Some examples are presented to establish the strength and applicability of this method. The results reveal that the method is very effective, straightforward, and simple to handle systems of boundary value problems

A comprehensive study of distributed Denial-of-Service attack with the detection techniques

With the dramatic evolution in networks nowadays, an equivalent growth of challenges has been depicted toward implementing and deployment of such networks. One of the serious challenges is the security where wide range of attacks would threat these networks. Denial-of-Service (DoS) is one of the common attacks that targets several types of networks in which a huge amount of information is being flooded into a specific server for the purpose of turning of such server. Many research studies have examined the simulation of networks in order to observe the behavior of DoS. However, the variety of its types hinders the process of configuring the DoS attacks. In particular, the Distributed DoS (DDoS) is considered to be the most challenging threat to various networks. Hence, this paper aims to accommodate a comprehensive simulation in order to figure out and detect DDoS attacks. Using the well-known simulator technique of NS-2, the experiments showed that different types of DDoS have been characterized, examined and detected. This implies the efficacy of the comprehensive simulation proposed by this study

Impact of loading capability on optimal location of renewable energy systems distribution networks

Copyright © 2023 The Authors. A distribution system's network reconfiguration is the process of altering the open/closed status of sectionalizing and tie switches to change the topological structure of distribution feeders. For the last two decades, numerous heuristic search evolutionary algorithms have been used to tackle the problem of network reconfiguration for time-varying loads, which is a very difficult and highly non-linear efficiency challenge. This research aims to offer an ideal solution for addressing network reconfiguration difficulties in terms of a system for power distribution, to decrease energy losses, and increase the voltage profile. A hybrid Genetic Archimedes optimization technique (GAAOA) has also been developed to size and allocate three types of DGs, wind turbine, fuel cell and PV considering load variation. This approach is quite useful and may be used in many situations. This technique is evaluated for loss reduction and voltage profile on a typical 33-bus radial distribution system and a 69-bus radial distribution system. The system has been simulated using MATLAB software. The findings suggest that this approach is effective and acceptable for real-time usage

A Double-Blind, Randomized, Placebo-Controlled Clinical Trial on Benfotiamine Treatment in Patients With Diabetic Nephropathy

OBJECTIVE - To investigate the effect of benfotiamine on urinary albumin excretion (UAE) and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24 h, despite ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), were randomly assigned to 12 weeks of benfotiamine (900 mg/day) (n = 39) or placebo (n = 43). RESULTS - Compared with placebo, benfotiamine treatment resulted in significant improvement of thiamine status (P <0.001). Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion. CONCLUSIONS - In patients with type 2 diabetes and nephropathy, high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion, despite improvement of thiamine status

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration &gt;= 5 years, cases of DN were defined as albuminuria &gt;300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In &lt;10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin