Temporal and Dosage Impact of Magnesium Oxide Nanoparticles on Grass Carp: Unveiling Oxidative Stress, DNA Damage and Antioxidant Suppression.

Magnesium oxide nanoparticles (MgO NPs) have gained significant importance in biomedicine and variety of nanotechnology-based materials used in the agriculture and biomedical industries. However, the release of different nanowastes in the water ecosystem becomes a serious concern. Therefore, this study was executed to evaluate the toxic impacts of MgO NPs on grass carp. A total of 60 grass carp were randomly divided in three groups (G0, G1, and G2). Fish reared in group G0 were kept as control while fish of groups G1 and G2 were exposed to 0.5mg/L and 0.7mg/L MgO NPs respectively, mixed in water for 21 days. The 96h median lethal concentration (LC50) of MgO NPs was found to be 4.5mg/L. Evaluation of oxidative stress biomarkers, antioxidant enzymes, DNA damage in different visceral organs and the presence of micronuclei in erythrocytes were determined on days-7, 14, and 21 of the trial. Results revealed a dose and time-dependent significantly increased values of reactive oxygen species, lipid peroxidation product, DNA damage in multiple visceral organs and formation of micronuclei in the erythrocytes of treated fish (0.7mg/L). The results on antioxidant profile exhibited significantly lower amounts of total proteins, catalase, superoxide dismutase and peroxidase in visceral organs of the fish exposed to MgO NPs (0.5 and 0.7mg/L) at day 21 of trial compared to control group. In conclusion, it has been recorded that MgO NPs severely influence the normal physiological functions of the grass carp even at low doses.

Association of eating disorders with glycaemic control and insulin resistance in patients of type 2 diabetes mellitus.

BACKGROUND: There is insufficient data on the prevalence and consequences of eating disorders in Type 2 diabetic patients. OBJECTIVE: To evaluate the presence of eating disorders (ED) and their association with glycaemic control and metabolic parameters in adult patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cross-sectional study on 145 patients was conducted in the medicine outpatient unit of HAHC Hospital, Jamia Hamdard tertiary care center. The Eating Attitudes Test (EAT-26) was used to screen for ED in adults with T2DM. The Score of less than 20 and more than 30 on EAT-26 questionnaire was defined as control for participants and relevant medical details like duration of treatment, glycaemic control, complications were recorded. RESULTS: A total of 145 diabetic individuals participated in this study. Out of these, 17.3% of individuals with T2DM screened positive for ED on EAT-26 scale and had a significant positive correlation in <20 groups and a significant negative correlation in >30 groups. CONCLUSION: Our study reveals that eating disorders are not very common in our clinical population of T2DM, the prevalence rates of eating disorders are lower in patients with T2DM than those reported from developed western countries.

COVID-19 and geriatric population: from pathophysiology to clinical perspectives.

The COVID-19 pandemic has not only led to a worldwide socio-economic depression, but has also had the highest health impact on the geriatric population. Elderly population, due to various reasons such as low immunity, pre-existing co-morbidities such as hypertension, cardiovascular diseases or diabetes, are obviously predisposed to develop severe infections and exhibit a high mortality rate. This is because of many reasons which include the atypical presentation in the geriatric population which might have led to diagnostic delay. As per the WHO guidelines to perform RT-PCR only on the symptomatic individuals, a very small portion of individuals were tested, leaving a fraction of population undiagnosed. Therefore, there remained a chance that many asymptomatic individuals such caregivers, healthcare professionals, family members were undiagnosed and might have carried this virus to the geriatric patients. Also, many countries were not prepared to handle the burden on their healthcare system which included sudden increased demand of ICU beds, mechanical ventilation etc. As a result, they had to make decision on who to be admitted. Atypical presentation in geriatric population may include afebrile or low-grade fever, absence of cough, malaise, muscle pains, dyspnoea etc. Geriatric population shows a more severe type of pneumonia, significantly higher number of neutrophils and C-reactive protein, less lymphocytes and a higher proportion of multiple lobe involvement. Extreme social suppression during COVID-19 pandemic has increased the risk of mental and physical adverse effects that has made older adults more vulnerable to depression and anxiety.

COVID-19 and cardiovascular disease: a review of current knowledge.

The uncontrolled spread of the COVID-19 pandemic which originated in China created a global turmoil. While the world is still busy figuring out a cure for the deadly disease, scientists worked out on many theories and conducted several studies to establish a relationship between the infection and other known diseases. Cardiovascular diseases (CVD) are one of the major complications of this infection after the respiratory manifestations. Individuals with cardiovascular complication are said to be more susceptible to acquiring the infection because the novel coronavirus uses the ACE2 receptor for its entry inside the cell and there is a high level of ACE2 expression in individuals with cardiovascular complications because of the enzyme's anti-hypertrophic, anti-fibrotic and anti-hypertensive effects on the heart. Individuals who belong to the older age group are also more susceptible. Knowing the above information, it might seem that using ACE2 inhibitors would help to slow or prevent the entry of the novel coronavirus but it would also at the same time prove to have deleterious effects on the cardiovascular system as the protective functions of ACE2 would be lost. While the search for a cure still continues it has been stated many a times that the conditions might worsen with time and the only way to keep ourselves and our family safe would be to follow the appropriate social distancing methods and get a COVID test if we experience any of the major symptoms.

Prevalence of elevated liver enzymes and its relationship with type 2 diabetes mellitus in North Indian adults.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) also referred as metabolic as metabolic (dysfunction) associated fatty liver disease. Type 2 diabetes mellitus (T2DM) is a major cause in progression of NAFLD and non-alcoholic steatohepatitis (NASH). The aim of the present study is to assess the activity of liver enzymes in T2DM in North Indian population. METHOD: This was a cross-sectional descriptive study clinic-based study in patients with T2DM. A total of 612 participants (226 healthy controls and 386 T2DM) were recruited. Body mass index (BMI), activity of liver enzymes including alanine and aspartate aminotransferase (ALT, AST) along with alkaline phosphatase (ALP) was measured. Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) along with total protein (TP) and albumin were also measured. Quantitative variables were expressed as mean ± SD, while qualitative variables as frequencies (%). Pearson/Spearman correlation test, unpaired t-test, Chi-squared test was used to assess the correlation, association and significant differences between study groups respectively. A P-value of < .05 was set as statistically significant. The Statistical Package for Social Sciences (SPSS) ® Statistics, version 23 (IBM SPSS Statistics, Armonk, NY) was used to for analysis of data. RESULTS: The study was conducted on 386 T2DM patients, and out of 386 patients, 139 (36.01%) were male (P < .000) and 247 (63.98%) were female. The mean age of the T2DM patients was 46.4 ± 13.6 years, while healthy individuals have mean age of 39.2 ± 12.0 years (P < .000). It was observed that the activity of AST in T2DM is comparable with the healthy persons (P = .060). While the level of ALT, total bilirubin and ALP in T2DM is significantly higher compared to healthy control (P < .000). On average, 62.53% of T2DM subjects and 32% of participants of healthy subjects had abnormal liver enzymes activity. CONCLUSION: The present study has revealed widely co-existent derangements in liver function tests (LFTs) in the diabetic population of North India. A detailed workup in such patients may be helpful in timely diagnosis and treatment. Moreover, early detection and management of abnormal liver parameters in T2DM would help minimize liver-related morbidity and mortality.

Methylglyoxal and soluble RAGE in type 2 diabetes mellitus: Association with oxidative stress.

PURPOSE: Methylglyoxal (MGO) and MGO related advance end product (AGE) are thought to contribute to the development of diabetes and its complications. The present study was intended to determine plasma MGO and sRAGE levels in T2DM patients and to assess the relationship between MGO and other parameters, such as sRAGE and oxidative markers. METHODS: The study was carried out in 100 control and T2DM subjects. Methylglyoxal, sRAGE, HbA1c, and other markers were measured by using a standard protocol and the relationship between variables was analyzed using Spearman's correlation analysis. RESULTS: Plasma MGO levels in patients with T2DM (221.1 ± 9.50 ng/mL) were significantly higher than in control subjects (121.1 ± 6.52 ng/mL, P < 0.001). The plasma level of MGO was positively correlated with glycosylated hemoglobin (HbA1c, r = 0.50, P < 0.001). Plasma soluble form of RAGE (sRAGE) was significantly decreased in T2DM subjects (5.3 ± 0.64 ng/mL) as compared to the control group (7.7 ± 0.86 ng/mL, p < 0.05). However, at increased level of glycation (HbA1c > 10%), the sRAGE level was 6.2 ± 0.42 ng/mL and was not statistically significant as compared to control healthy group (> 0.05). Moreover, we have not found any correlation between MGO and other markers (p > 0.05). CONCLUSIONS: The findings of the present study showed that increased plasma MGO level is significantly associated with the HbA1c levels in T2DM patients. Moreover, the study shows that plasma sRAGE level is significantly augmented at increased level of glycation (HbA1c > 10%) in T2DM patients.

Protein creatinine index: A possible predictor of nephropathy in hypertensives, in Northern India.

BACKGROUND: >33% of the hypertensive Indians develops nephropathy. Proteinuria is an early indicator of nephropathy. Gold standard for determining proteinuria is 24-hour urinary protein excretion which is a troublesome task with poor patient compliance. Protein creatinine index (PCI) in a random urine sample has been advocated by some researchers as an alternative approach. Aim of this study was to evaluate the association of PCI with the severity and duration of hypertension, in North Indian population. METHODS: 120 Stage-1 hypertensives, 120 stage-2 hypertensives, 40 pre-hypertensives and 40 normotensives were included in this study. 240 Hypertensive subjects were divided into 3 sub-groups based on duration: <5years (n=80), 5-10years (n=80) and >10years (n=80). Urinary protein was estimated by sulfosalicylic acid method and urinary creatinine was measured using modified Jaffe's method. PCI was measured as described by Shaw et al. Data was statistically analyzed by ANOVA and Pearson's correlation test using SPSS v20. RESULTS: PCI of stage-2 hypertensives (157.83±51.53) was significantly higher than normo-, pre- and stage-1 hypertensives. PCI of stage-1 hypertensives (134.15±46.04) was significantly higher than normotensives only. PCI of hypertensives for 5-10years (137.29±49.55) and >10years (181.85±47.42) was significant higher than controls and pre-hypertensives. PCI showed significantly stronger association with severity (r=0.595) and duration (r=0.745) of hypertension as compared to urinary protein and creatinine concentration. Data also suggest that the risk of renal injuries against the backdrop of raised blood pressure (BP) increases after 5years of hypertension. CONCLUSION: PCI can be used as a screening tool for early detection of hypertensive nephropathy. PCI monitoring should be incorporated in the routine checkup module of patients suffering from hypertension for >5years.

Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: glycated-histones as likely trigger for SLE?

Histones are the most abundant proteins associated with genomic DNA. Recent observations show that histones are quite susceptible to non-enzymatic glycation which results in the generation of free radicals causing structural perturbations. In this study, our aim is to define the role of deoxyribose-modified H2A histone in SLE initiation/progression. Glycation reaction was carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 °C. Structural changes in glycated-H2A were studied by various physico-chemical techniques. The antigen-antibody interaction was studied by direct binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A histone showed increased hyperchromicity and increased fluorescence intensity. CD results demonstrated almost 50% loss in alpha helix conformation as a consequence of glycation. This was supported by an increase in Tm value vis-à-vis thermal stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone compared to native H2A histone or native DNA. Inhibition ELISA supported the above findings. Band shift assay further reiterated the preferential recognition of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified-H2A histone exhibited damage as revealed by various physico-chemical studies. Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone, which are preferably bound by SLE anti-nDNA autoantibodies. It implies that deoxyribose-modified-H2A may trigger immune response resulting in the generation of anti-glycated H2A antibodies with DNA cross reacting properties.

Alpha-1 antitrypsin, a diagnostic and prognostic marker of vernal keratoconjunctivitis.

INTRODUCTION: A major chunk of ocular allergies in humans involve the conjunctiva, of which Vernal Keratoconjunctivitis (VKC) appears to be more common. VKC, a chronic allergic conjunctivitis, frequently affects young males and is characterized by intense inflammation of the limbal and/or tarsal conjunctiva. The etiology and immuno-pathogenesis of VKC still remain unclear. Alpha-1 antitrypsin (AAT), a member of serine proteinase inhibitor (SERPIN) superfamily, is an acute phase protein whose concentration in blood increases in response to inflammation. AAT deficiency is one of the many factors that may be involved in several abnormalities such as liver disease, emphysema, inflammatory joint diseases and inflammatory eye diseases. In the present study, the role played by this protein in VKC was analyzed in a selective case/control study to assess its diagnostic and prognostic value. MATERIALS AND METHODS: The case control study included 50 patients of VKC reporting to Ophthalmology out patient department (OPD). Age and sex matched 40 healthy subjects served as control. Serum AAT level of both the cases and controls were evaluated and compared. Moreover the serum AAT levels of the patients at presentation were compared with their serum AAT level after three weeks post treatment. RESULT: Levels of AAT in the serum of VKC patients at presentation (2.80 ± 0.42 mg/ml) were significantly higher as compared to controls (2.31 ± 0.21 mg/ml) whereas no significant difference was observed between the serum level of post treatment VKC patients (2.48 ± 0.26 mg/ml) and controls. CONCLUSION: AAT is a potent acute phase protein whose concentration rises significantly in VKC, irrespective of the age and sex of the patient. Moreover, the serum level of AAT declined significantly post treatment; therefore it might be used as a prognostic marker.

Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy.

To study the role of one of the most potent motoneuron (MN) survival factors, glial cell line-derived neurotrophic factor (GDNF) derived from the CNS, we generated transgenic animals overexpressing GDNF under the control of an astrocyte-specific GFAP promoter. In situ hybridization revealed that GDNF was expressed at high levels in astrocytes throughout the brain and spinal cord. We analyzed the effects of CNS-derived GDNF on MN survival during the period of programmed cell death (PCD) and after nerve axotomy. In GFAP-GDNF mice at E15, E18, and P1, the survival of brachial MNs was increased on average by 30%, lumbar MNs by 20%, and thoracic MNs at P1 by 33%. GDNF also prevented MN PCD in several cranial motor nuclei. We demonstrated for the first time that the number of MNs in the mouse abducens nucleus was also increased by 40%, thus extending known MN populations that are responsive to GDNF. Next, we tested if GDNF could support complete and relatively long-term survival of MNs following neonatal facial nerve axotomy. We found that virtually all MNs (91%) in GFAP-GDNF mice survived for up to 18 weeks post-axotomy. This is the longest GDNF-mediated survival of neonatal MNs reported following axotomy. Most of surviving MNs were not atrophic, and MN-specific ChAT and neurofilament immunoreactivity (IR) were preserved. Furthermore, GDNF attenuated axotomy-induced astroglial activation. These data demonstrate that overexpression of GDNF in the CNS has very profound effects on MN survival both during the PCD period and after neuronal injury. GFAP-GDNF mice will be valuable to study the effects of CNS-derived GDNF in mouse models of MN degenerative diseases and axonal regeneration in vivo.