Anti-glycating and anti-cytotoxic effect of silibinin on albumin at early glycation: A physiochemical study.

During persistent hyperglycaemia, albumin, one of the major blood proteins, can undergo fast glycation. It can be expected that timely inhibition of protein glycation might be add quality years to diabetic patients' life. Therefore, this study was designed to analyse the role of silibinin to reduced or delay amadori adduct formation at early glycation and its beneficial effect to improve the glycated albumin structure and conformation. We also analysed cytotoxic effect of amadori-albumin in the presence of silibinin on murine macrophage cell line RAW cells by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. Formation of early glycated product (furosine) in all samples was confirmed by LCMS. Albumin incubated with glucose only showed presence of furosine like structure. Albumin treated with silibinin in the presence of glucose did not show such furosine like peak. This LCMS result showed the silibinin play a protective role in the formation of early glycated product. HMF contents were also reduced in the presence of silibinin, when albumin was incubated with increasing concentrations of silibinin (100 and 200 µM) in the presence of glucose. ANS binding fluorescence decrease by increasing silibinin concentrations with amadori-albumin. SDS-PAGE was also showed that no significant difference in the band mobility of albumin treated with silibinin as compared to native albumin. The secondary conformational alteration in amadori-albumin due to silibinin were confirmed by FTIR. This spectrum showed slight shift in amide I and Amide II band in albumin co-incubated with glucose and silibinin as compared to albumin incubated with glucose only. We further discussed about cytotoxic effect of amadori albumin and its prevention by silibinin. MTT assay results demonstrated that amadori-albumin showed cytotoxic effect on RAW cells but silibinin showed protective role and increased the cell viability. Moreover, the results showed that silibinin has anti-glycating potential and playing a role to prevent the formation of Amadori-albumin in-vitro. Silibinin possesses strong anti-glycating capacity and can improve albumin structure and function at early stage. It might be useful in delaying the progression of diabetes mellitus and its secondary complications at early stage.

Assessment of quality of work life (QWL) among healthcare staff of intensive care unit (ICU) and emergency unit during COVID-19 outbreak using WHOQoL-BREF.

OBJECTIVE: The study aimed to document the quality of work life (QWL) among healthcare staff of intensive care units (ICUs) and emergency units during COVID-19 outbreak using the WHOQoL-BREF. METHODS: A multicenter cross-sectional study was conducted for two months (May - June 2020) among healthcare staff working in intensive care units (ICUs) and emergency units of the hospitals under the National Guard Health Authority (NGHA) across five cities of Saudi Arabia. The study used the WHOQoL-BREF instrument to document the QWL through an electronic institutional survey. The data was analyzed through IBM SPSS version 23. The study was approved by an ethics committee. RESULTS: A total of 290 healthcare professionals responded to the survey. The mean overall quality of life score was 3.37 ± 0.97, general health = 3.66 ± 0.88, domains, i.e., physical = 11.67 ± 2.16, psychological = 13.08 ± 2.14, social = 13.22 ± 3.31 and environment = 12.38 ± 2.59. Respondents aged > 40 years, male gender, married status, being a physician and, having a work experience > 15 years and no extra working hours, had higher mean scores for several domains of Quality of life (QoL), overall QoL and general health (p < 0.05). CONCLUSION: The QWL among healthcare staff during COVID-19 pandemic was low. Demographic factors were mainly the determinants for a higher QWL while the variable of extra working hours was a determinant of lower QWL. Despite the pandemic, no COVID-19 related variables affected the work life of healthcare staff.

A study on correlation between oxidative stress parameters and inflammatory markers in type 2 diabetic patients with kidney dysfunction in north Indian population.

BACKGROUND: Research reports support the statement that oxidative stress and inflammation are well-known risk factors for chronic kidney disease (CKD) in patients with diabetes. This study was designed to ascertain the associated role of oxidative stress parameters and inflammatory markers in diabetes and related CKD among the north Indian population. METHODS: The study was divided into three groups as healthy subjects (group 1), patients with diabetes without complication (group 2), and with CKD (group 3). Serum levels of malondialdehyde (MDA) and nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) content were estimated in all individuals. Inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)-α were determined by enzyme-linked immuno-sorbent assay. RESULTS: MDA, protein carbonyl, and NO were significantly elevated in patients with type 2 diabetes as compared with healthy subjects (P ≤ 0.05). Total thiols content were found to be significantly decreased in patients with diabetes with CKD. The activity of antioxidant enzymes SOD, CAT, and GR showed a significant suppression in patients with type 2 diabetes with or without CKD as compared with healthy subjects. Nevertheless, the levels of proinflammatory cytokines IL-6 and TNF-α were significantly upregulated ( P ≤ 0.05) as compared with healthy subjects. CONCLUSION: Determination of antioxidant defense parameters and inflammatory markers contributes to understand the relationship between oxidative stress and inflammation on the development and prevention of chronic kidney disease in Indian patients with diabetes.

Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review.

The aim of the review is to examine the role of growth factors and cytokines in the management of Diabetic Foot Ulcers, such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and Insulin like growth factor (IGF). Taking this a step further, the role of Hypoxia-inducible factors (HIFs), Transforming growth factor beta 1 (TGF-ß-1) and other growth factors have also been examined, with regard to the treatment of diabetic foot ulcers. The roles of these above-mentioned growth cytokines have been analyzed by studying various scholastic articles. The complete process of wound healing is implemented and regulated by numerous cytokines and human growth factors. The findings of the study indicate that wound healing of diabetic foot ulcers is a complex and extremely challenging biological and molecular process that involves coordinated efforts of multiple cell types. The therapeutic effects of various growth factors in the clinical management of wounds are chronic venous ulcers, pressure ulcers, and diabetic foot ulcers. It has been concluded that altercations of various cytokines are found in patients enduring diabetic foot ulcers. In a similar way, changes in the level of cytokines are also found in patients suffering from other diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy. Subsequently, the diabetic wound healing process can be accelerated by regulating the levels of the cytokines.

MFSC: Multi-voting based feature selection for classification of Golgi proteins by adopting the general form of Chou's PseAAC components.

Automatic identification of protein subcellular localization has gained much popularity in the last few decades. Subcellular localizations are useful in diagnosis of different diseases as well as in the process of drug development. Golgi is a vital type of protein, which provides means of transportation to several other proteins destined for lysosome, plasma membrane and secretion etc. Cis-Golgi and trans-Golgi are two ends of Golgi protein meant for reception and transmission of various substances. Dysfunction in Golgi proteins may lead to different types of diseases especially the inheritable and neurodegenerative problems. Due to the significance of Golgi proteins, it is indispensable to correctly identify the Golgi proteins. In this paper, a novel and high throughput computational model is proposed which can identify the subGolgi proteins precisely. Discrete and evolutionary feature extraction schemes are applied so that all the salient, noiseless, and relevant information from protein sequences could be captured. Unfortunately, the benchmark dataset publicly available is quite imbalance, where trans-Golgi sequences constitute 72% of the whole dataset that reflects biasness, redundancy, and lack of hypothesis generalization. In order to cover the limitations of imbalance data, Synthetic Minority over Sampling Technique is utilized to balance the number of instances in different classes of the dataset. In addition, a condense feature space is formed by fusing the high rank features of eleven different feature selection techniques. The high rank features are selected through majority voting algorithm; consequently, the feature space is reduced 85%. The experiential results demonstrate that kNN classifier obtained promising results in combination with hybrid feature space. It has yielded an accuracy of 98% in jackknife cross-validation, 94% in independent data and 96% in 10-fold cross-validation test. It is ascertained that the proposed model is reliable, consistent and serves as a valuable tool for the research community.

Study of IL4-590C/T and IL6-174G/C Gene Polymorphisms in Type 2 Diabetic Patients With Chronic Kidney Disease in North Indian Population.

To explore the associations between potential functional promoter polymorphisms in pro-inflammatory and anti-inflammatory (IL-4(-590C/T) and IL-6(-174G/C) cytokine genes, and kidney dysfunction in North Indian type 2 diabetic subjects with chronic kidney disease. A total of 150 subjects aged 25-75 year were included in this study. The glomerular filtration rate (GFR) and serum creatinine were estimated. PCR was performed to analyse genotype distribution in IL-4 (-590T/C) and IL-6 (-174G/C) among healthy, type 2 diabetic patients with or without CKD. The genotype distributions were determined by Hardy-Weinberg equilibrium. CKD patients showed lower GFR (59.36 ± 1.33 ml/min/1.73 m2 ) and higher serum creatinine (1.93 ± 0.99% mg) level in comparison to diabetic patients without CKD and healthy subjects. Genotypic distribution of the different genotypes among the study groups in IL-4 gene was genotype CC = 30, TC = 12, and TT = 8 in CKD patients. In type 2 diabetic patients without CKD, genotype distribution was CC = 38, TC = 10, and TT = 2. In healthy subjects, distribution of genotype was CC = 35, TC = 14, and TT = 1. The distribution of different genotype among the study groups for IL-6 gene was GG = 27, GC = 20, and CC = 3 in healthy subjects; GG = 28, GC = 19, and CC = 3 in diabetic patients without CKD and GG = 38, GC = 11, and CC = 1 in diabetic patients with CKD. There was no significant difference in the distribution of genotype frequencies between healthy subjects and diabetic patients without CKD but a significant difference was found in diabetic patients with CKD. The functional promoter polymorphisms IL4-590C/T and IL6-174G/C, which affect the IL-4 and IL-6 levels in north Indian subjects, were associated with kidney dysfunction and CKD. J. Cell. Biochem. 118: 1803-1809, 2017. © 2016 Wiley Periodicals, Inc.

An overview of in vitro and in vivo glycation of albumin: a potential disease marker in diabetes mellitus.

Non-enzymatic glycation of macromolecules, especially proteins leading to their oxidation is increased in diabetes mellitus due to hyperglycaemia and play an important role in associated complications of the disease. Protein glycation mostly occurs in intra chain lysine residues resulting in the formation of early stage Amadori products which are finally converted to advance glycation end products (AGEs). This review deals with the structural studies of in vitro and in vivo glycated human serum albumin (HSA). The aim of this review is to explain the disturbance in secondary and tertiary structure of albumin upon glucosylation and the immunogenic potential of modified albumin. Amadori-albumin may have enough potential to provoke the immunoregulatry cells and generate autoantibodies in diabetic patients. Role of Amadori-albumin in the induction of autoantibodies in type2 diabetes especially in chronic kidney disease (CKD) patients has been discussed. This review also considers various studies that investigate the effects of glycation on the structural and immunological properties of HSA. The use of glycated albumin (GA) as a short to intermediate term marker for glycaemic control in diabetes is also focused.

A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration.

Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28 days at 37°C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC-MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients' sera with disease duration of 5-15 years exhibited significantly high binding with DNA-AGE as compared to patients with 1-5 years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients.

High yield expression of novel glutaminase free L-asparaginase II of Pectobacterium carotovorum MTCC 1428 in Bacillus subtilis WB800N.

Gene encoding glutaminase-free L-asparaginase II (ans B2) from Pectobacterium carotovorum MTCC 1428 was cloned into pHT43, transformed in Bacillus subtilis WB800N and optimised the expression levels of recombinant enzyme. A three-fold higher enzyme production was observed with an efficient transformant as compared to native strain. Enzyme localization studies revealed that >90% of recombinant enzyme is secreted extracellularly, a little fraction is attached to the membrane (>6%) and localised intracellularly (3%). The expression of recombinant L-asparaginase II was confirmed by SDS-PAGE, IMAC (Immobilised metal ion affinity chromatography) purification followed by Western blotting. Process parameter optimization with OFAT (one factor at a time) revealed that rpm (120), temperature (37 °C), Isopropyl ß-D-1-thiogalactopyranoside (IPTG) concentration (1 mM) and time of induction (0.8 OD600nm) plays a vital role where a maximum of 55 IU/ml was achieved. Further, consecutive induction by IPTG improved the enzyme production up to 105 IU/ml with a specific activity of 101 IU/mg of protein. Molecular modelling analysis depicted that amino acids, GLY60, GLY119 and ALA252 in the active site are responsible for the glutaminase free L-asparaginase II activity. This is the first report on enhanced expression of recombinant glutaminase-free L-asparaginase II by intermediate addition of IPTG.

The proximal fibula should be examined in all patients with ankle injury: a case series of missed maisonneuve fractures.

BACKGROUND: The Maisonneuve fracture is a spiral fracture of the proximal third of the fibula. It occurs from violent twisting of the ankle that characteristically causes ligament damage and severe instability. Most patients complain of significant ankle pain but very little pain over the fracture. The clinical and radiographic examination is usually directed to the ankle region; and the proximal fibula is often ignored. OBJECTIVE: The authors intend to show the ease of missing the proximal fibular fracture when the clinical examination is directed to the ankle region. They discuss the importance of palpating the proximal fibula and ordering appropriate radiographs. CASE STUDIES: The authors report on 5 patients who presented to the Emergency Department, where the Maisonneuve fracture was missed despite having ankle radiographs taken. All patients required open reduction and internal fixation. CONCLUSION: The Maisonneuve fracture injury pattern causes untoward consequences if not promptly recognized and treated. To avoid misdiagnosis, the proximal fibula should be examined in all patients with ankle injury.

Treatment of myotendinous Achilles ruptures.

BACKGROUND: There is scant literature regarding the treatment of myotendinous Achilles ruptures. The purpose of this study was to retrospectively examine clinical outcomes from uniform nonsurgical treatment of these injuries. METHODS: Between November 2005 and May 2011, 30 patients presented with an acute, complete myotendinous Achilles rupture. The location of the Achilles injury was confirmed on magnetic resonance imaging (MRI) for all patients. All patients were treated nonsurgically, which involved 3 weeks of non-weight-bearing and then 3 weeks of progressive to full weight-bearing in an Achilles boot. Physical therapy was provided for 4 to 6 weeks after this period of immobilization. 21 patients were male and 9 were female. The patients had a mean age of 40.8 years (range, 24-54). Patients were followed an average of 40.5 months (range, 23-81). RESULTS: Full healing of the Achilles myotendinous junction was achieved clinically in all 30 patients . All patients experienced improved function and less pain at their latest follow-up. Mean Foot and Ankle Ability Measure-Sports (FAAM-Sports) increased from 20.2% at the time of initial presentation to 95.2% at the latest follow-up (P < .05). Mean Visual Analog Scores (VAS) of pain decreased from 8.2 at the time of initial presentation to 1.3 at latest follow-up (P < .01). In all, 23 (76.7%), 6 (20%), and 1 (3.3%) patients rated their satisfaction as excellent, good, and fair, respectively. No patients have developed recurrent myotendinous Achilles ruptures to date. CONCLUSION: Nonsurgical treatment of myotendinous Achilles ruptures results in a high rate of myotendinous healing with improved patient function and pain relief. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Association of Sensory Nerve Action Potential Amplitude and Velocity With Type 2 Diabetic Peripheral Neuropathy.

BACKGROUND: There is ongoing controversy regarding the predominant type of nerve injury in diabetic peripheral neuropathy, whether it is demyelination or axonal degeneration. OBJECTIVE: This study aimed to investigate the association between nerve conduction study parameters, specifically nerve conduction velocity and the amplitude of the action potential, with diabetic peripheral neuropathy and determine their potential as early indicators of the condition. METHODS: A cross-sectional study was conducted involving diagnosed type 2 diabetes mellitus patients, who were divided into two groups: Group I (n = 111) with symptomatic diabetic peripheral neuropathy and Group II (n = 109) without clinically detectable peripheral neuropathy. Age and sex-matched healthy controls (n = 100) were also included. Nerve conduction velocity measurements were performed on both upper and lower limbs, with motor nerve conduction study focusing on the dominant side using the median and posterior tibial nerves and sensory nerve conduction study using the median and sural nerves. RESULTS: The nerve conduction studies revealed significantly lower sensory nerve action potential amplitudes and compound muscle action potential amplitudes in the median, posterior tibial, and sural nerves of the diabetic groups compared to the control subjects. Furthermore, these changes were more prominent in patients with peripheral neuropathy. Among the 220 diabetic patients analyzed, 135 (61.36%) exhibited nerve conduction abnormalities. The highest rate of abnormality was observed in the sural nerve, followed by the posterior tibial and median nerves. The most common abnormality detected in diabetic patients was a decrease in sensory nerve action potential, followed by a decrease in sensory nerve conduction velocity. CONCLUSION: The study findings suggest an association between reduced sensory nerve action potential amplitude and diabetic peripheral neuropathy. These results highlight the potential of sensory nerve action potential and velocity as a sensitive indicator of peripheral neuropathy in diabetic patients.

Impact of Type 2 Diabetes Mellitus with a Focus on Asian Indians Living in India and Abroad: A Systematic Review.

BACKGROUND: Diabetes is a highly prevalent disease in the world. Type 2 diabetes mellitus (T2DM) is growing at an alarming rate due to rapid urbanization, migration, aging population, and lifestyle changes. INTRODUCTION: We have summarized the global T2DM distribution in specific International Diabetes Federation (IDF)-defined regions and various countries and highlighted the high risk of T2DM prevalence in Asian Indians living in India and worldwide. METHODS: A systematic review was conducted using combinations of the following key concepts 'T2DM'; 'global distribution'; 'Asian Indians'; 'high risk' and 'prevalence' by searching PubMed and EMBASE databases for articles describing the global distribution of T2DM. From 430 searched articles, 54 full-text articles were reviewed to study the distribution, risk, and prevalence of diabetes in various countries. RESULTS: As per IDF Atlas, 463 million people in 2019 have diabetes worldwide, and it is expected to rise to 700 million by 2045. The global distribution of T2DM differs from various countries to various regions. Asia is the epicenter of diabetes, where 60% of people with diabetes live, mainly in China (139.9 million) and India (65 million). South Asians are more susceptible to developing T2DM as compared to ethnic Europeans. Asian Indians living worldwide are at a high risk of developing T2DM. Those who have migrated to various countries (USA, UK, Australia, Singapore, Mauritius, New Zealand, Fiji, etc.) have a higher prevalence of T2DM than the native population and even more significant than those Indians living in India due to being more insulin resistant. Indians develop T2DM at a younger age and at a lower BMI due to genetic makeup and behavioral and environmental determinants, including diet and sedentary lifestyle and westernization. CONCLUSION: In conclusion, insulin levels were found to be higher not only in adults but also in adolescents and young adults. In addition, rapid urbanization, migration, industrial modernization, and lifestyle changes are other factors responsible for the development of T2DM.

Thermomechanical Modeling of Material Flow and Weld Quality in the Friction Stir Welding of High-Density Polyethylene.

A thermomechanical model of the friction stir welding (FSW) of high-density polyethylene (HDPE) was developed by incorporating a Coupled Eulerian-Lagrangian (CEL) approach. A Johnson Cook (JC) material model of HDPE was developed through experimentally generated strain-rate- and temperature-dependent stress strain data. Two sets of FSW process parameters with minimum and maximum weld defects were numerically modeled. The numerically calculated temperature distribution, material flow and flash and potential defects were validated and discussed with the experimental results. Tracer particles allowed to visualize the material movement during and after the tool had traversed from the specified region of the workpiece. Both numerical models presented similar maximum temperatures on the upper surface of the workpiece, while the model with high traverse speed and slow rotational speed had narrower shoulder- and heat-affected zones than the slow traverse, high rotational speed model. This contributed to the lack of material flow, hence the development of voids and worm holes in the high traverse speed model. Flash and weld defects were observed in models for both sets of process parameters. However, slow traverse, high rotational speeds exhibited smaller and lesser weld defects than high traverse, slow rotational speeds. The numerical results based on the CEL approach and JC material model were found to be in good agreement with the experimental results.

Congenital erythropoietic porphyria presenting with recurrent epistaxis: a case report.

BACKGROUND: Congenital erythropoietic porphyria (CEP), also known as pink tooth or Gunther disease, is a rare hereditary disorder caused by an enzyme mutation in the heme biosynthesis pathway, which leads to the accumulation of immature and non-physiological protoporphyrin rings in various tissues. CEP is characterized by sun-exposed bullous skin lesions, hemolytic anemia, red/brown urine, and teeth staining. CASE PRESENTATION: We present a unique case of a 10-year-old Asian boy with CEP who presented with recurrent epistaxis, an unusual presentation for this condition. Based on clinical presentation and laboratory findings, including elevated urine uroporphyrin and coproporphyrin I and III levels, microcytic anemia, a higher red cell distribution width (RDW), and a lower platelet count, a thorough assessment and detailed workup resulted in a diagnosis of CEP. The patient underwent a successful splenectomy and recovered without any complications. CONCLUSION: This case report aims to raise awareness among healthcare professionals about the uncommon and atypical presentation of CEP and its management options.

A Study of the Friction Stir Lap Welding of AA5052 and Polypropylene.

Friction stir lap welding (FSLW) remains a pioneering technique for creating hybrid joints between AA5052 aluminium alloy and polypropylene (PP), particularly with the metal-on-top configuration. Building upon previous research, this study introduces a tapered fluted pin tool design and investigates its effectiveness in the welding process. Our results, supported by ANOVA, chemical, and microstructural analyses, reiterate that the optimal welding parameters stand at a rotational speed of 1400 RPM and a traverse speed of 20 mm/min. This combination produces a joint tensile strength of 3.8 MPa, signifying 16.54% of the weaker material's inherent strength. Microstructural evaluations revealed a unique composite of aluminium chips intermeshed with PP, strengthened further by aluminium hooks. Crucially, mechanical interlocking plays a predominant role over chemical bonding in achieving this joint strength. The study underscores the absence of significant C-O-Al bonds, hinting at the PP degradation without the thermo-oxidation process. Additionally, joint strength was found to inversely correlate with the interaction layer's thickness. The findings fortify the promise of FSLW with the novel fluted pin design for enhancing joints between AA5052 and PP, emphasising the potential of mechanical interlocking as a principal factor in achieving high-quality welds.

Threat of Antimicrobial Resistance among Pilgrims with Infectious Diseases during Hajj: Lessons Learnt from COVID-19 Pandemic.

Hajj pilgrimage is a large mass gathering global event that may facilitate the spread and emergence of various infectious diseases as well as antimicrobial resistance (AMR) in a local and global scenario. Planning and preparing for these public health issues is a challenging and complex process for the Kingdom of Saudi Arabia (KSA) health authorities. Despite multiple efforts for the prevention and treatment of infectious diseases through longtime funding in education and medical care, the prevalence of infectious disease is still high among Hajj pilgrims. The commonly observed infectious diseases during Hajj include respiratory tract infections (influenza and pneumonia), urinary tract infections and skin infections that may necessitate the use of antimicrobials. Beta-lactams are used as a first-line treatment for hospital acquired infections as well as community acquired infections due to their broad-spectrum activity. However, most of the bacterial isolates such as Staphylococcus spp., Pseudomonas spp. and E. coli are resistant to beta-lactams. Irrational use of antimicrobials, lack of infection prevention practices and suboptimal healthcare access further exacerbate the risk of spreading AMR among Hajj pilgrims. Enhanced collaboration between countries, sharing of best practices and international cooperation are crucial in addressing AMR threats among pilgrims. Consequently, robust surveillance systems for early detection and monitoring of AMR, collaboration with national as well as international healthcare agencies, effective infection prevention and control measures, public awareness and rational use of antimicrobials via antimicrobial stewardship programs are required to mitigate the risk of AMR and ensure the health and well-being of pilgrims during Hajj.

Dose optimization of vancomycin in obese patients: A systematic review.

Background: Dose optimization of vancomycin plays a substantial role in drug pharmacokinetics because of the increased incidence of obesity worldwide. This systematic review was aimed to highlight the current dosing strategy of vancomycin among obese patients. Methods: This systematic review was in concordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The literature search was carried out on various databases such as Scopus, PubMed/MEDLINE, ScienceDirect and EMBASE using Keywords and MeSH terms related to vancomycin dosing among obese patients. Google Scholar was also searched for additional articles. The English language articles published after January, 2000 were included in this study. The quality of the study was assessed using different assessment tools for cohort, and case reports. Results: A total of 1,029 records were identified. After screening, 18 studies were included for the final review. Of total, twelve studies are retrospective and remaining six are case-control studies. A total of eight studies were conducted in pediatrics while remaining studies were conducted in adult population. Most of the studies reported the dosing interval every 6-8 h. Differences in target trough concentration exist with respect to target ranges. The administration of loading dose (20-25 mg/kg) followed by maintenance dose (15-25 mg/kg) of vancomycin is recommended in adult patients to target therapeutic outcomes. Moreover, a dose of 40-60 mg/kg/day appears appropriate for pediatric patients. Conclusion: The initial dosing of vancomycin based on TBW could be better predictor of vancomycin trough concentration. However, the clinical significance is uncertain. Therefore, more studies are needed to evaluate the dosing strategy of vancomycin in overweight or obese patients.

Structural and immunological characterization of Amadori-rich human serum albumin: role in diabetes mellitus.

Proteins modifications in diabetes may lead to early glycation products (EGPs) as well as advanced glycation end products (AGEs). Whereas no extensive studies have been carried out to assess the role of EGPs in secondary complications of diabetes, numerous investigators have demonstrated the role of AGEs. Early glycation involves attachment of glucose on ε-NH2 of lysine residues of proteins leading to generation of the Amadori product (an early glycation species). This study reports the structural and immunological characterization of EGPs of HSA because we believe that during persistent hyperglycemia the HSA, one of the major blood proteins, can undergo fast glycation. Glucose mediated generation of EGPs of HSA was quantitated as Amadori products by NBT assay and authenticated by boronate affinity chromatography and LC/MS. Compared to native HSA changes in glycated-HSA were characterized by hyperchromicity, loss in fluorescence intensity and a new peak in the FTIR profile. Immunogenicity of native- and glycated-HSA was evaluated by inducing antibodies in rabbits. Results suggest generation of neo-epitopes on glycated-HSA rendering it highly immunogenic compared to native HSA. Quantization of EGPs of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes.

Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress.

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.