Inhibition of protein glycation and advanced glycation end products by ascorbic acid

Advanced glycation end products (AGEs) formation is increased in diabetes mellitus, leading to microvascular and macrovascular complications. Recently, much attention has been focused on natural and synthetic inhibitors to delay the onset or progression of diabetes and its comorbidities. Ascorbic acid (AA) can react with proteins, including hemoglobin and possibly interfere with protein glycation process. An in vitro glycation model containing plasma from type 2 diabetic and non-diabetic healthy volunteers together with glucose as glycating agent was used to study antiglycation activity of AA. Samples with different concentrations of glucose and AA were incubated for five weeks at 37°C. Nonenzymatic glycation (NEG) was quantitated by thiobarbituric acid calorimetry and AGEs were measured by enzyme linked immuno-sorbent assay (ELISA). The NEG and AGEs levels were reduced by AA. Increasing the AA concentrations greatly diminished protein glycations, indicating dose-dependent effects of AA. Plasma NEG and AGEs were decreased with an average of 20 to 26% (p < 0.05) and 26 to 28% (p < 0.05). A significant correlation was found between the glycation inhibition and the inhibition of AGE formation (p < 0.05). The antiglycation role of AA is evident in the present study and it also indicates the possibility of inexpensive, relatively non-toxic vitamin therapy for the prevention and treatment of diabetic complications. It is plausible that AGEs inhibition by AA may also form the basis for future intervention strategies in both diabetic and non-diabetic individuals.Keywords: Diabetes mellitus, glycation, advanced glycation end products, hyperglycemia, ascorbic aci

Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe

Aqueous extracts of Zingiber officinale rhizomes were studied to evaluate their antidiabetic effects on protein glycation and on the diffusion of glucose in vitro in the present study. Zingiber officinale rhizome aqueous extract were examined at concentrations of 5, 10, 20 and 40 g/L. The antidiabetic effects were found to be dose-dependent. Antidiabetic potential of Zingiber officinale was mainly through inhibition of the glucose diffusion and to a limited extent by reducing the glycation. However, further studies are needed to determine in vitro effects of therapeutic potential by restraining postprandial glucose absorptions and plasma protein glycations in diabetic subjects.Extratos aquosos de rizomas Zingiber officinale foram estudados para avaliar os seus efeitos antidiabéticos em glicação de proteínas e sobre a difusão de glicose in vitro, no presente estudo. Extratos aquosos de Zingiber officinale foram examinados nas concentrações de 5, 10, 20 e 40 g extrato de planta/L. Os efeitos antidiabéticos observados eram dependentes da dose. O potencial antidiabético de Zingiber officinale se verificou, principalmente, através da inibição da difusão de glicose e, em menor extensão, através da redução da glicação. Estudos adicionais são necessários para elucidar se efeitos in vitro representam potencial terapêutico, restringindo a absorção de glicose pós-prandial e a glicação de proteínas plasmáticas em indivíduos diabéticos

Poboljšanje proizvodnje glukoza-oksidaze s pomoću Penicillium notatum

Glucose oxidase (GOD) is an important enzyme that finds a wide range of applications in food and pharmaceutical industry. In this investigation the feasibility of using rice polish as a substrate for the production of GOD by Penicillium notatum in submerged fermentation (SmF) has been evaluated. The intention was to enhance total GOD activity by the selection of economical substrate, microorganism and consecutive optimization of various cultural conditions. Maximum GOD activity of (112±5) U/mL was achieved under optimum growth conditions: rice polish 5 g, incubation period 72 h, buffering agent 3 % (by mass per volume), incubation temperature (30±1) °C and pH=6.0. Addition of carbon and nitrogen sources further enhanced the enzyme yield, indicating an economically attractive process for GOD production.Glukoza-oksidaza je važan enzim koji ima raznovrsnu primjenu u industriji hrane i proizvodnji lijekova. U ovome je radu ispitana primjena otpadaka dobivenih poliranjem riže kao supstrata u proizvodnji glukoza-oksidaze submerznom fermentacijom s pomoću Penicillium notatum. Svrha je rada bila poboljšati ukupnu aktivnost glukoza-oksidaze odabirom ekonomičnog supstrata i mikroorganizma te optimiranjem uvjeta uzgoja. Najveća aktivnost od (112±5) U/mL postignuta je pri optimalnim uvjetima rasta uporabom 5 g otpadaka i 3 % (m/V) puferskog sredstva tijekom 72 h pri (30±1) °C i pH=6. Dodatkom izvora ugljika i dušika još je više poboljšan prinos enzima, čime je potvrđena ekonomska opravdanost ovog procesa za proizvodnju glukoza-oksidaze

Poboljšanje proizvodnje glukoza-oksidaze s pomoću Penicillium notatum

Glucose oxidase (GOD) is an important enzyme that finds a wide range of applications in food and pharmaceutical industry. In this investigation the feasibility of using rice polish as a substrate for the production of GOD by Penicillium notatum in submerged fermentation (SmF) has been evaluated. The intention was to enhance total GOD activity by the selection of economical substrate, microorganism and consecutive optimization of various cultural conditions. Maximum GOD activity of (112±5) U/mL was achieved under optimum growth conditions: rice polish 5 g, incubation period 72 h, buffering agent 3 % (by mass per volume), incubation temperature (30±1) °C and pH=6.0. Addition of carbon and nitrogen sources further enhanced the enzyme yield, indicating an economically attractive process for GOD production.Glukoza-oksidaza je važan enzim koji ima raznovrsnu primjenu u industriji hrane i proizvodnji lijekova. U ovome je radu ispitana primjena otpadaka dobivenih poliranjem riže kao supstrata u proizvodnji glukoza-oksidaze submerznom fermentacijom s pomoću Penicillium notatum. Svrha je rada bila poboljšati ukupnu aktivnost glukoza-oksidaze odabirom ekonomičnog supstrata i mikroorganizma te optimiranjem uvjeta uzgoja. Najveća aktivnost od (112±5) U/mL postignuta je pri optimalnim uvjetima rasta uporabom 5 g otpadaka i 3 % (m/V) puferskog sredstva tijekom 72 h pri (30±1) °C i pH=6. Dodatkom izvora ugljika i dušika još je više poboljšan prinos enzima, čime je potvrđena ekonomska opravdanost ovog procesa za proizvodnju glukoza-oksidaze

Delineation of nutrient management zones in Chunian using soil attributes database developed by soil fertility research institute, Punjab, Pakistan

A significant increase in food production, approximately 70%, is needed to feed the estimated 9.1 billion world population by 2050. Site-specific nutrient management through adoption of Precision Agriculture (PA) technologies can potentially increase crop productivity while keeping the use of chemical fertilizers at its minimum required level. In this study, agricultural land of tehsil Chunian was delineated into management zones using georeferenced soil attributes database developed by Soil Fertility Research Institute (SFRI), Punjab. Appropriate number of zones was determined after conducting fuzzy c -means unsupervised clustering analysis by using Management Zone Analyst (MZA) software and finally Quantum Geographic Information System (QGIS) was used to differentiate study area into five zones. Analysis of variance was performed to verify whether these defined zones reflect soil attributes. We concluded that tehsil Chunian could be categorized into five statistically different management zones based on soil electrical conductivity (EC), pH, soil organic matter (SOM), available potassium and available phosphorus levels. The highest crop yield was predicted in southeastern parts of tehsil Chunian represented by management zone-2 (4.4 t ha-1) followed by zone-1 (4.3 t ha-1). Whereas, northern and northwest areas were predicted with decreasing trend of wheat yield (zone-5, 3.7 t ha-1; zone-4, 4.0 t ha-1), respectively. We found that MZA and QGIS software could be used as supportive tools for making informed-decisions and the database of soil attributes developed by SFRI would serve as primary source of information for adoption of PA technology in coming years

Detection, quantification and genotype distribution of HCV patients in Lahore, Pakistan by real-time PCR

Background: Hepatitis C virus (HCV) is considered as \u201cViral Time Bomb\u201d suggested by the World Health Organization and if it is not treated timely, it will lead towards cirrhosis and hepatocellular carcinoma (HCC). Objective: The purpose of the present research is to study possible risk factors, frequent genotypes of HCV and its association with different age groups. Methods: Suspected blood samples from HCV patients were collected from different hospitals of Lahore, Pakistan. Out of 1000 HCV suspected samples, 920 samples were found HCV positive detected by Anti-HCV ELISA, CobasR. kit. The quantification of HCV load was determined by HCV quantification kit and LINEAR ARRAY KIT (Roche) was used for genotype determination by Real-Time PCR (ABI). Statistical analysis was done by using Microsoft Excel. Results: Out of 920 subjects, 77 subjects (8.4%) were false positive and they were not detected by nested PCR. Three PCR positive samples were untypeable. Genotype 3 was predominant in Lahore which was 83.5%, whereas type 1 and 2 were 5.1% and 0.7% respectively. There were also mixed genotypes detected, 1 and 3 were 0.4%, 2 and 3 were 1.41% and 3 and 4 were 0.2% only. Male were more infected of HCV in the age <40 years and females >40years. Conclusion: The major risk factor for HCV transmission is by use of unsterilized razors/blades. It is necessary to spread awareness among the general population of Pakistan about HCV transmission risk factors. Regular physical examination at least once a year is recommended, so that early detection of HCV could be done

Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe

Aqueous extracts of Zingiber officinale rhizomes were studied to evaluate their antidiabetic effects on protein glycation and on the diffusion of glucose in vitro in the present study. Zingiber officinale rhizome aqueous extract were examined at concentrations of 5, 10, 20 and 40 g/L. The antidiabetic effects were found to be dose-dependent. Antidiabetic potential of Zingiber officinale was mainly through inhibition of the glucose diffusion and to a limited extent by reducing the glycation. However, further studies are needed to determine in vitro effects of therapeutic potential by restraining postprandial glucose absorptions and plasma protein glycations in diabetic subjects.Extratos aquosos de rizomas Zingiber officinale foram estudados para avaliar os seus efeitos antidiabéticos em glicação de proteínas e sobre a difusão de glicose in vitro, no presente estudo. Extratos aquosos de Zingiber officinale foram examinados nas concentrações de 5, 10, 20 e 40 g extrato de planta/L. Os efeitos antidiabéticos observados eram dependentes da dose. O potencial antidiabético de Zingiber officinale se verificou, principalmente, através da inibição da difusão de glicose e, em menor extensão, através da redução da glicação. Estudos adicionais são necessários para elucidar se efeitos in vitro representam potencial terapêutico, restringindo a absorção de glicose pós-prandial e a glicação de proteínas plasmáticas em indivíduos diabéticos

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations.Peer reviewe