Association of single nucleotide polymorphism rs3213119 variant of IL-12B gene in diagnosed Rheumatoid Arthritis patients.

Objective: To identify the IL12B gene variant (rs3213119) and to find its association in Pakistani clinical population of Rheumatoid Arthritis. Methods: It was a population association (unrelated) case control study, performed from January - December 2022 at Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi. Blood samples were collected from all 150 study participants, followed by DNA extraction and Allele-specific polymerase chain reaction performed at Center for Research in Experimental and Applied Medicine (CREAM) Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' (version-22), followed by gene analysis on 'SNPstat'. Results: About 28.0% of RA patients were smokers, 38.7% had history of RA in a first degree relative and 70.7% had positive history of consanguinity. Considering rs3213119 variant of IL12B gene, frequency of major allele C was 100%, minor allele A was 21%, genotype C/C was 79% and C/A was 21%. Applying the log additive model, the odds ratio of the genotype C/C was 1.00 (adjusted by age and gender with 95 % CI) and the odds ratio of the genotype C/A was 0.00, 52.0% of RA patients originated from four predominant ethnic groups, namely Awaans (18.7%), Rajputs (14.7%), Pathans (12.0%) and Araeens (6.7%). Conclusion: The study findings suggest the role of minor allele 'A' as risk allele in our clinical population. CA genotype confers susceptibility towards the RA development.

Significance of serum ferritin and De Ritis ratio in non-alcoholic fatty liver disease as diagnostic markers.

Objectives: To ascertain the significance of serum ferritin and De Ritis ratio as diagnostic markers in patients of nonalcoholic fatty liver disease with and without type 2 diabetes mellitus. METHODS: The comparative cross-sectional study was conducted from February to October 2022 at the Radiology Department of Combined Military Hospital, Rawalpindi, Pakistan, and comprised individuals aged 30-65 who were divided into 3 groups. Healthy controls formed group I, non-alcoholic fatty liver disease patients without type 2 diabetes mellitus formed group II and non-alcoholic fatty liver disease patients with type 2 diabetes mellitus were in group III. Blood 5ml was withdrawn and assessed for alkaline phosphatase, aspartate transaminase, alanine transaminase and ferritin. De Ritis ratio was calculated and subjected to intergroup comparison. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 110(52.4%) were males and 100(47.6%) were females, with 70(33.3%) in each of the three groups. Group I had 38(54.3%) females and 32(45.7%) males with mean age 37.50±4.513. In group II, there were 27(38.6%) females and 43(61.4%) males with mean age 45.86±9.646, while in group III there were 35(50%) females and 35(50%) males with mean age 54.01±9.243 years. Serum ferritin levels were significantly increased in patient groups II and III compared to control group I (p<0.05). De Ritis ratio was markedly raised in groups II and III compared to group I (p<0.05). Ferritin was significantly correlated to age, weight, height, fasting blood glucose, haemoglobin, alkaline phosphatase, aspartate aminotransferase, alanine transaminase and bilirubin (p<0.05). De Ritis ratio had a significant correlation with body mass index and fasting blood glucose (p<0.05). CONCLUSIONS: Serum ferritin and De Ritis ratio were found to be useful diagnostic indicators for non-alcoholic fatty liver disease, highlighting their importance in improving disease screening.

Comparison of oxidative stress, lipid peroxidation and inflammatory markers between rheumatoid arthritis and ankylosing spondylitis patients.

Objectives: To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis and ankylosing spondylitis. METHODS: The comparative, cross-sectional study was conducted from February 2 to December 30, 2022, at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi. The sample comprised healthy controls in group 1, patients of rheumatoid arthritis in group 2 and patients of ankylosing spondylitis in group 3. Blood samples were assessed for levels of superoxide dismutase, malondialdehyde, erythrocyte sedimentation rate and C-reactive protein. Data was analysed using SPSS 25. RESULTS: Of the 180 subjects, 60(33.3%) were in group 1; 32(53.3%) females and 28(46.7%) males with mean age 34.9±6.4 years. There were 60(33.3%) patients in group 2; 35(58.3%) females and 25(41.7%) males with mean age 46.0±11.1 years. There were 60(33.3%) patients in group 3, and all 60(100%) were males with mean age 35.9±6.9 years. Superoxide dismutase level was significantly low and malondialdehyde level was significantly high in groups 2 and 3 compared to group 1 (p<0.05). Erythrocyte sedimentation rate was the highest in group 2, followed by group 3 (p<0.05). C-reactive protein levels were the highest in group 2 and the lowest in group 3 (p<0.05). A significantly negative correlation (p<0.001) was found between superoxide dismutase and malondialdehyde. CONCLUSIONS: Oxidative stress played a pivotal role in chronic inflammatory rheumatic diseases, like rheumatoid arthritis and ankylosing spondylitis.

Demographic analysis of hearing impairment based on various parameters in patients with cochlear implant.

Objectives: To analyse the demographic and clinical variables in children having undergone cochlear implant surgery because of deafness. METHODS: The cross-sectional study was conducted from January to November 2022 at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Ear, Nose and Throat Department of Combined Military Hospital, Rawalpindi, and comprised children of eith gender aged up to 10 years who had received cochlear implant. Data was collected through questionnaire-based detailed interviews. Syndromic Hearing Loss, Non-Syndromic Hearing Loss, and Acquired Hearing Loss were identified among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 250 cases, 147(58.8%) were boys, 146(58.4%) were aged 0-5 years, 219(87.6%) had prelingual onset of disease, and 202(80.8%) had a non-progressive disease course. In 203(81.2%) cases, normal developmental milestones were seen. Parental consanguinity was observed in 219(87.6%) cases. However, 63(25.2%) patients had a first-degree relative who had a history of deafness. In 170(68%) cases, hearing loss was hereditary, whereas in 80(32%) it was acquired. Meningitis was the most commonly identified risk factor 55(68.75%). Acquired risk factors and family history had significant association with hearing loss (p<0.05). Speech perception significantly improved in all 219(100%) patients with prelingual hearing loss who underwent cochlear implantation. CONCLUSIONS: Majority of the cases were found to be male, had a prelingual disease onset and a non-progressive disease course. Family history was a significant factor, while meningitis was the most common acquired cause of hearing loss.

Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy.

Objective: To determine the association of diabetic nephropathy with glyoxalase-1 enzyme levels and a genetic missense variation (SNP rs4746) in its gene (GLO-1). Methods: This cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi from November 2020 to December 2022. One hundred patients and one hundred and thirteen healthy controls were enrolled using the nonprobability convenience sampling method. Medical history and 10ml blood were obtained from each individual after written informed consent. Blood samples were subjected to biochemical tests and DNA extraction which was later used for single nucleotide polymorphism (SNP) analysis (C332C variant of rs4741 GLO-1 gene) using Tetra primer ARMS PCR and gel electrophoresis. Glyoxalase-1 enzyme activity in serum was measured using ELISA. Results: There was a significant difference in serum glyoxalase-1 levels in the two groups (p-value< 0.001). The patient group had lower levels (16.24 ± 22.51mg/dl) of glyoxalase-1 as compared to the control group (48.70 ± 42.54mg/dl). In genotypic analysis, 98 out of 100 control individuals had AA genotype-while only one had CC and another AC genotype. In the patient group, 94 out of 100 patients showed AA genotype, three AC, and three CC genotypes. As the statistical significance (p-value) was 0.37, there was no significant association found between AC or CC genotype and diabetic nephropathy. Conclusion: Glyoxalase-1 levels are linked to the development of diabetic nephropathy in our patients while a known missense variant rs4746 in the GLO-1 gene is not associated with increased risk.

Association of serum IL12 with clinical and biochemical parameters in a cohort of diagnosed rheumatoid arthritis patients on oral conventional synthetic disease modifying anti-rheumatic drugs.

Objective: To determine the association of serum interleukin-12 levels with disease progression in active rheumatoid arthritis patients on oral conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: The case-control study was conducted at the Army Medical College, Rawalpindi, in collaboration with the Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2022, and comprised rheumatoid arthritis patients or either gender aged 18-75 years who were placed in group I, while group II comprised healthy controls. Demographic and clinical data was noted, and 2ml blood samples were drawn from each subject. The serum was separated and analysed using sandwich enzyme-linked immunosorbent assay to quantify serum interleukin-12 levels. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, 75(50%) were in group I; 27(36%) males and 48(64%) females with overall mean age 45.70±11.70 years. There were 75(50%) subjects in group II; 37(49.3%) males and 38(50.7%) females with overall mean age 31.70±7.70 years. Serum interleukin-12, erythrocyte sedimentation rate and C-reactive proteinquantitative levels were significantly higher in group I compared to group II (p<0.05). Smoking, positive family history of rheumatoid arthritis in a first-degree relative and history of consanguinity were identified as risk factors though they were not statistically significant (p>0.05). In group I (n=75), out of total study subjects, only 55(73.3%) cases belonged to the predominant castes, namely Awan, Rajput, Pathan, Araeen, Bhatti, Malik, Mughal, Sudhan, Chaudary, and Jutt. These individuals showed significantly higher mean serum interleukin-12 levels compared to patients of other castes in the same group. Conclusion: Mean serum interleukin-12 levels were higher in rheumatoid arthritis patients despite being on oral conventional synthetic disease-modifying anti-rheumatic drugs.

Comparison of Platelets-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios in Rheumatoid Arthritis and Ankylosing Spondylitis.

OBJECTIVE: To calculate and compare the platelets-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), to be used as a complementary diagnostic tool in patients of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). STUDY DESIGN: Cross-sectional, comparative study. Place and Duration of the Study: Pak Emirates Military Hospital (PEMH), Rawalpindi, from February to November 2022. METHODOLOGY: A total of two hundred and ten patients, aged between 25 to 70 years, were included in the study. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) along with platelets, leukocyte, and neutrophil count were estimated. PLR and NLR were calculated and compared between the groups. RESULTS: The PLR was significantly high in the RA group (p-value <0.001) followed by AS and control groups. NLR also followed the same trend and was significantly raised in both the disease groups as compared to controls. Pearson correlation depicted significant positive correlation between PLR and ESR (r = 0.43, p <0.001), NLR and ESR (r = 0.34, p <0.001), PLR and CRP (r = 0.15, p = 0.034) and NLR and CRP (r = 0.18, p = 0.018). Logistic regression analysis displayed the diagnostic value of PLR and NLR. CONCLUSION: Both PLR and NLR are effective as complementary diagnostic indices in RA and AS patients. These may be used in addition to the inflammatory markers ESR and CRP as cost-effective and promptly available indices. KEY WORDS: Ankylosing spondylitis, Platelets-lymphocyte ratio, Neutrophils-lymphocyte ratio, Rheumatoid arthritis.

Oxidative Stress and Lipid Peroxidation in NAFLD with and without Type 2 Diabetes Mellitus.

OBJECTIVE: To compare superoxide dismutase 1 (SOD 1) and malondialdehyde (MDA) levels along with biochemical parameters in patients of non-alcoholic fatty liver disease (NAFLD) with and without Type 2 diabetes mellitus. STUDY DESIGN: Cross-sectional comparative study. Place and Duration of the Study: Centre for Research in Experimental and Applied Medicine, AMC, in collaboration with the Department of Radiology, Combined Military Hospital, Rawalpindi, from February to November 2022. METHODOLOGY: Two hundred and ten patients were selected by non-probability purposive sampling and divided into 3 groups. Healthy individuals were labelled as Group Ι, Group II included patients of NAFLD without diabetes mellitus, and Group III had patients of NAFLD with diabetes mellitus. Fasting blood glucose levels and lipid profile were measured. ELISA (enzyme-linked immunoassay) was done for the assessment of SOD 1 and MDA levels. The data was analysed by version 22.0 of SPSS and expressed in mean ± SD and percentage. One-way ANOVA was done for all groups and grade comparison was followed by the post-hoc Tukey test. RESULTS: When compared to control groups, the mean SOD 1 level in diseased groups was significantly lower (p<0.001). There was a statistically significant difference between each group (p<0.001). Mean levels of MDA were significantly increased in diseased groups as compared to controls with a statistically significant difference between all groups except between Group II and III. CONCLUSION: In patients having NAFLD with and without diabetes mellitus, SOD 1 levels were considerably lower compared to controls whereas MDA levels were significantly higher. This decrease in SOD 1 and raise in MDA levels was indicative of increased oxidative stress in patients and can be viewed as a biomarker for oxidative stress. KEY WORDS: NAFLD, ELISA, Oxidative stress, SOD 1, MDA, Lipid peroxidation.

Expression analysis of ABCA1 in type 2 diabetic Pakistani patients with and without dyslipidemia and correlation with glycemic index and lipid profile.

Diabetes Mellitus type II, earlier considered as an endocrinological disorder is now more regarded as an inflammatory disorder along with lipid aberrations. It demands for regular monitoring, healthy dietary habits and lifestyle modification. This study was focused on gene expression of ATP binding cassette protein 1 (ABCA1) in diabetic dyslipidemia patients in comparison with control groups of only diabetics and healthy individuals. Blood samples and data were collected from recruited 390 patients who were further divided into three groups (130 each). Glycemic index and lipid profile was assessed. Delta Delta Ct method was used that revealed downregulation of the studied gene more in diabetic dyslipidemia patients as compared to only diabetics and healthy controls. The Ct values of ABCA1 were associated with glycemic index and lipid profile using Pearson's correlation. A negative correlation with fasting blood sugar and a positive correlation with HbA1cwas observed in only diabetics group. While in diabetic dyslipidemia and normal healthy controls, a negative correlation was found with both. As far as the lipid profile is concerned a positive correlation was observed among only diabetics with whole lipid profile. In diabetics with dyslipidemia, a negative correlation with all parameters except the TAGs was observed. A positive correlation with all except HDL was observed in healthy controls. The Ct values and fold change were compared among diseased and healthy individuals by applying independent t test. The cycle threshold in only diabetics was p = 0.000018 and in diabetic dyslipdemia individuals was p = 0.00251 while fold change in only diabetics (p = 0.000230) and in diabetics with dyslipidemia (p = 0.001137) was observed to be as statistically significant.

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects.

Objective: To find possible association of R1939W and P1987R variants of OTOF gene with severe to profound NSSHL in cochlear implant subjects. Methods: It was a case control study, conducted from June 2021 to February 2022, comprising 50 cases of severe to profound NSSHL who had received cochlear implant from ENT Department, CMH Rawalpindi and 50 age-matched healthy controls from PEMH Rawalpindi. Blood samples were collected from all the subjects, followed by DNA extraction and allele-specific polymerase chain reaction, performed at Multi-disciplinary Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' and 'XLSTAT', followed by genetic analysis using 'SNPstat'. Results: Mean age of the cases was 5.96 ± 4.62 years (N=50), comprising 58% males and 42% females. All had bilateral and prelingual HL. Parental consanguinity was 72%, whereas 62% cases had a positive family history of deafness. Alleles of R1939W and P1987R were not associated with NSSHL, as shown by their p values of 0.56 and 0.89 respectively. For R1939W ORs were 0.71 (dominant model) and 0.80 (overdominant model), indicating negative association with NSSHL. Regarding P1987R OR was 0.96 (log-additive model). Genotypes of both variants were not in HW Equilibrium (p <0.0001), whereas their alleles showed high LD (D'=0.92). Conclusion: High percentage of parental consanguinity was observed among cochlear implant candidates. The OTOF variants R1939W and P1987R were found to have protective roles against NSSHL in study population.

Identification and Association of Polymorphism rs2073618 of the Osteoprotegerin Gene in Type 2 Diabetics with and without Retinopathy.

OBJECTIVE: To identify and determine the association of SNP (rs2073618) of OPG gene in diabetics with and without retinopathy and in healthy controls. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi in collaboration with Chemical Pathology Laboratory, Pak Emirates Military Hospital, Rawalpindi and Armed Forces Institute of Ophthalmology, Rawalpindi, from June 2021 to May 2022. METHODOLOGY: Participants aged 25-70 years were inducted and divided into three equal groups. Group I consisted of diabetics with retinopathy (n = 50), group II was diabetics without retinopathy (n = 50), and group III was healthy individuals (n = 50). DNA was extracted and allele specific PCR technique was adopted using specifically designed primers. Results were analysed using the software Statistical Package for Social Sciences (SPSS) version 22.0 and online bio-informatics tool SNPstats. RESULTS: CC, CG, and GG genotypes were found to be present in 94%, 4%, and 2% in diabetics without retinopathy, 92%, 4%, and 4% in diabetics with retinopathy, respectively, and 100% presence of CC genotype only in healthy controls. C and G alleles were present in 96% and 4%, respectively, in diabetics without retinopathy, with 100% presence of only C allele in healthy subjects. The genotypic assessment using the models showed no significant association. CONCLUSION: SNP rs2073618 of OPG gene was identified in all study groups without any significant distribution or association with the development of diabetic retinopathy. The major genotype C/C was found in the majority of subjects in all groups. KEY WORDS: Allele specific PCR, Diabetic retinopathy, Single nucleotide polymorphism, Type 2 Diabetes mellitus.

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Acute Kidney Injury Complicating Wasp Stings: A Report of Two Cases and Literature Review.

Acute kidney injury could occasionally complicate wasp stings. We describe two such cases. The first one developed acute kidney injury as a result of rhabdomyolysis and hemolysis, whereas the other patient developed acute kidney injury as part of multiorgan dysfunction syndrome resulting from shock and rhabdomyolysis. Both remained dependent on intermittent hemodialysis for a short period of time before recovering spontaneously. These cases highlight different pathophysiological processes leading to acute kidney injury, and the importance of timely diagnosis to achieve favourable clinical outcomes.

Aldose reductase gene polymorphism rs752010122 and retinopathy in type 2 diabetics.

Objectives: To investigate the association of polymorphism in rs752010122 in aldose reductase gene with the pathogenesis of diabetic retinopathy, and to determine the association and allelic frequency between the variant and the disease. METHODS: The cross-sectional study was conducted from June 2021 to March 2022 at Centre for Research in Experimental and Applied Medicine (CREAM) Laboratory, Department of Biochemistry and Molecular Biology, Army Medical College, in collaboration with the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, and comprised blood samples from subjects of either gender aged 40-70 years. The samples were divided into group I having diabetic retinopathy patients, group II having diabetics without retinopathy, and group III having healthy controls matched for age and gender. The samples were subjected to molecular analysis. Gene sequence was downloaded from the Human Genome Database and Ensemble. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, there were 50(33.3%) in each of the 3 groups. Variants of aldose reductase rs752010122 polymorphism were significantly associated with a lower risk of diabetic retinopathy (p<0.05). An odds ratio of 1 was noted for both heterozygous and homozygous genotypes (95% confidence interval: 1). CONCLUSIONS: Aldose reductase was associated with lower risk of the disease.

Effect of Scanning Strategy on Thermal Stresses and Strains during Electron Beam Melting of Inconel 625: Experiment and Simulation.

This paper develops a hybrid experimental/simulation method for the first time to assess the thermal stresses generated during electron beam melting (EBM) at high temperatures. The bending and rupture of trusses supporting Inconel 625 alloy panels at ~1050 °C are experimentally measured for various scanning strategies. The generated thermal stresses and strains are thereafter simulated using the Finite-Element Method (FEM). It is shown that the thermal stresses on the trusses may reach the material UTS without causing failure. Failure is only reached after the part experiences a certain magnitude of plastic strain (~0.33 ± 0.01 here). As the most influential factor, the plastic strain increases with the scanning length. In addition, it is shown that continuous scanning is necessary since the interrupted chessboard strategy induces cracking at the overlapping regions. Therefore, the associated thermal deformation is to be minimized using a proper layer rotation according to the part length. Although this is similar to the literature reported for selective laser melting (SLM), the effect of scanning pattern is found to differ, as no significant difference in thermal stresses/strains is observed between bidirectional and unidirectional patterns from EBM.

Risk Analysis and Assessment of Lipid Abnormalities as the Earliest Complication in Newly Diagnosed Diabetic and Non-Diabetic Individuals of a Local Population.

Lipid variations have been frequently observed in global populations that can affect health status. Mainly studies have been conducted on the type 2 diabetic population, but limited data is available on newly diagnosed ones to unravel complications and risk predictors independent of disease progression. This study comprising 244 individuals was carried out to assess the lipid abnormalities in newly diagnosed diabetics and non-diabetics. The clinical and socio-demographic data were collected and analyzed using independent samples t-test and linear regression. Serum lipid variations were observed individually and in combination. The individuals in group I (diabetics with dyslipidemia) revealed elevated levels of low-density lipoprotein and serum triglycerides higher than in group II (non-diabetics with dyslipidemia). The frequency of deranged total cholesterol in group I was observed to be higher than in group II. Independent samples t-test showed a significant mean difference in variables between the two groups. Linear regression analysis showed a significant variable outcome for predictors between high-density lipoprotein (HDL) and physical activity (B= -0.043, 95% CI: -0.80, -0.006) and total cholesterol (TC) with family history (B= -0.062, 95% CI: -0.123, -0.001). The findings conclude that lipid levels deranged independently regardless of type 2 diabetes mellitus and present as an early onset in type 2 diabetes instead of later stage complication. These derangements of lipid levels are an independent risk factor for future cardiovascular pathology.

Comparative effects of tocopherol and ubiquinol on arsenic induced nephrotoxicity in sprague dawley rats.

Millions of the people worldwide are drinking arsenic polluted water. The need of time is to find out the mitigation strategies to cope with this issue. To evaluate the effects of tocopherol and ubiquinol individually and collectively on arsenic induced nephrotoxicity in Sprague Dawley rats. 150 Sprague Dawley rats were divided into 5 groups randomly. Animals of group I were provided with distilled water and sterile diet pellets. All other groups were given arsenic contaminated water (5mg/L) ad libitum. Moreover, ubiquinol and tocopherol (250mg/kg each) were given to group III and IV rats respectively. Whereas, both tocopherol and ubiquinol (125mg/kg each) was given to rats of group V. After 2 weeks of intervention period, serum RFTs were evaluated on micro lab. After exposure to arsenic, animals of group II showed a significant (p<0.01) elevation of serum RFTs. Treatment with ubiquinol in group III animals and tocopherol in group IV animals reduced the levels (p<0.01) of serum RFTs in these groups. Whereas, the combined effects of both these antioxidants reversed these changes to normal values (p>0.05). Both tocopherol and ubiquinol (synergistically) are more efficient in minimizing the nephrotoxicity induced by arsenic.

Determination of Pleiotropic Effect of Warfarin in VKORC1 and CYP2C9 Genotypes in Patients With Heart Valve Replacement.

Warfarin has been widely used as an oral anticoagulant agent. In past, efforts have been done to study the contribution of genetic variation on warfarin dose requirements. The possible therapeutic dose determination of warfarin is very challenging, i.e., extremely low dose leading to unusable antithrombotic therapy or high dose causes particularly bleeding complications. Our study aimed to investigate these observations in more detail, we determined the correlation of interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) among VKORC1 and CYP2C9 genetic variants in patients with heart valve replacement who were treated with a range of warfarin doses and compared with levels in healthy controls. A total of 107 human subjects were recruited with low < 5 mg, medium 5-10 mg/day, and high > 10 mg/day warfarin doses. The genetic study of VKORC1-1639G/A, C1173T, 3730G > A, CYP2C9*2, and CYP2C9*3 was performed using TaqMan genotyping and DNA sequencing. The gene expression of IL-6, TNF-α, and COX-2 mRNA was analyzed. IL-6, TNF-α, and COX-2 protein expressions were determined by ELISA and Western blot analysis to evaluate the pro- and anti-inflammatory effects of warfarin. A statistically significant difference was found among the haplotypes of VKORC1 rs9934438 (C1173T), rs9923231 (-1639G > A), rs7294 (3730G > A) and CYP2C9 *2 p. Arg144 Cys (rs28371674), CYP2C9 *3 p. Ile359Leu (rs1057910) genotypes with warfarin dose requirements (p = 0.001). The increased levels of COX-2, IL-6, and TNF-α proteins were observed when a high dose of warfarin (>10 mg/ml) was administered. However, a lower concentration (1.0 mg/ml) was observed with decreased warfarin dose (<5 mg/day). The present study reported that in addition to its anticoagulant action, the genetic variants of warfarin may have a pleiotropic effect by influencing IL-6 depending on the dosing regimen and inducing the expression of COX-2.

Effects of badminton insole design on stress distribution, displacement and bone rotation of ankle joint during single-leg landing: a finite element analysis.

Previous research has reported that up to 92% of injuries amongst badminton players consist of lower limb, whereby 35% of foot fractures occurred at the metatarsal bone. In sports, insoles are widely used to increase athletes' performance and prevent many injuries. However, there is still a lack of badminton insole analysis and improvements. Therefore, this study aimed to biomechanically analyse three different insole designs. A validated and converged three-dimensional (3D) finite element model of ankle-foot complex was developed, which consisted of the skin, talus, calcaneus, navicular, three cuneiform, cuboid, five metatarsals and five phalanges. Three existing insoles from the market, (1) Yonex Active Pro Truactive, (2) Victor VT-XD 8 and (3) Li-Ning L6200LA, were scanned using a 3D scanner. For the analysis, single-leg landing was simulated. On the superior surface of the skin, 2.57 times of the bodyweight was axially applied, and the inferior surface of the outsole was fixed. The results showed that Insole 3 was the most optimum design to reduce peak stress on the metatarsals (3.807 MPa). In conclusion, the optimum design of Insole 3, based on the finite element analysis, could be a justification of athletes' choices to prevent injury and other complications.