Genotoxic and oxidative stress-inducing effects of deltamethrin in the erythrocytes of a freshwater biomarker fish species, Channa punctata Bloch

Deltamethrin, an alpha-cyano class of pyrethroid insecticide is used in insect pest control and antimalaria programs in several countries including India. Although various toxic manifestations of deltamethrin are reported in mammals, its ecotoxicologic dimensions are not adequately researched in ecologically and commercially important fishes. In this study, we report genotoxic effect of deltamethrin in a biomarker fish Channa punctata (Bloch). Adult fish were exposed to three concentrations of technical grade deltamethrin (0.4, 0.8, and 1.2 microg/L) for 48 and 72 h. Ethyl methane sulfonate was used as a positive control. Fish were analyzed for induction of micronucleus (MN), nuclear abnormalities (NAs), and oxidative stress biomarkers in erythrocytes. Deltamethrin significantly induced MN and NAs accompanied by increased lipid peroxidation. Activity of antioxidant enzyme superoxide dismutase was significantly decreased but an increase was observed in reduced glutathione level after 72 h of exposure. The NAs in exposed fish included blebbed, lobed and notched nuclei, and binucleated erythrocytes. Our findings suggest that oxidative stress may, in part, be contributing to deltamethrin-induced genotoxic damage to erythrocytes. Although MN induction is a nonspecific biomarker, it may provide an indication of pollution load of deltamethrin in the affected fish population when used as part of suite of other biomarkers.     

Quality of life of very young spina bifida patients after initial surgical treatment

Objective

The objectives of this study were to assess the quality of life (QOL) of operated patients with spina bifida (SB) in their initial years and to elucidate the factors affecting the QOL and the timing of proposed interventions.

Patients and methods

We studied 18 patients operated on for SB, aging 3?years or more at the time of assessment. The quality of life score was calculated for all the patients by the parental-administered questionnaire method. The impact of all these factors on the social and school lives of these patients was studied.

Results

Eleven patients were having neurogenic bladder. Thirteen patients were having stool problems which ranged from mild to severe constipation and soiling. Five patients were having lower limb deformities interfering with normal ambulation. Ten patients were able to walk on their own without any help, four patients were using either crutches or help of the caregiver for ambulation while the remaining four patients were non-ambulatory. Twelve patients were attending school. The calculated QOL scores ranged from 2 to 15. The Barthel Index (BI) ranged from 15 to 100. The QOL questionnaire score and BI were showing significant positive correlation.

Conclusions

The patients operated on for SB commonly have the neurological sequelae. The QOL score identifies the important problems in the initial years after surgery which can help in initiating and maintaining rehabilitative services in these patients. The treatment of urinary and fecal incontinence very early in life will allow these children to have a normal social and school life.     

Oxidative stress causes renal dopamine D1 receptor dysfunction and hypertension via mechanisms that involve nuclear factor-kappaB and protein kinase C

Renal dopamine, via activation of D1 receptors, plays a role in maintaining sodium homeostasis and BP. There exists a defect in renal D1 receptor function in hypertension, diabetes, and aging, conditions that are associated with oxidative stress. However, the exact underlying mechanism of the oxidative stress-mediated impaired D1 receptor signaling and hypertension is not known. The effect of oxidative stress on renal D1 receptor function was investigated in healthy animals. Male Sprague-Dawley rats received tap water (vehicle) and 30 mM L-buthionine sulfoximine (BSO), an oxidant, with and without 1 mM tempol for 2 wk. Compared with vehicle, BSO treatment caused oxidative stress and increase in BP, which was accompanied by defective D1 receptor G-protein coupling and loss of natriuretic response to SKF38393. BSO treatment also increased NF-kappaB nuclear translocation, protein kinase C (PKC) activity and expression, G-protein-coupled receptor kinase-2 (GRK-2) membranous translocation, and D1 receptor serine phosphorylation. In BSO-treated rats' supplementation of tempol decreased oxidative stress, normalized BP, and restored D1 receptor G-protein coupling and natriuretic response to SKF38393. Tempol also normalized NF-kappaB translocation, PKC activity and expression, GRK-2 sequestration, and D1 receptor serine phosphorylation. In conclusion, these results show that oxidative stress activates NF-kappaB, causing an increase in PKC activity, which leads to GRK-2 translocation and subsequent D1 receptor hyper-serine phosphorylation and uncoupling. The functional consequence of this phenomenon was the inability of SKF38393 to inhibit Na/K-ATPase activity and promote sodium excretion, which may have contributed to increase in BP. Tempol reduced oxidative stress and thereby restored D1 receptor function and normalized BP.     

Investigating the Microstructural and Mechanical Properties of Novel Ternary Reinforced AA7075 Hybrid Metal Matrix Composite

This study investigates the comparison of the microstructural and mechanical properties of a novel ternary reinforced AA7075 hybrid metal matrix composite. Four samples, including AA7075 (base alloy), AA7075-5wt %SiC (MMC), AA7075-5wt %SiC-3wt %RHA (s-HMMC), and AA7075-5wt %SiC-3wt %RHA-1wt %CES (n-HMMC) were developed using the stir casting liquid metallurgy route, followed by the heat treatment. The experimental densities corresponded with the theoretical values, confirming the successful fabrication of the samples. A minimum density of 2714 kg/m³ was recorded for the n-HMMC. In addition, the highest porosity of 3.11% was found for n-HMMC. Furthermore, an increase of 24.4% in ultimate tensile strength and 32.8% in hardness of the n-HMMC was recorded compared to the base alloy. However, its ductility and impact strength was compromised with the lower values of 5.98% and 1.5 J, respectively. This was confirmed by microstructural analysis, which reveals that n-HMMC has mixing issues and forms agglomerates in the matrix, which served as the potential sites of stress concentration leading to low impact strength and ductility. Nevertheless, the hybrid composites showed superior mechanical properties over the MMC and its base alloy.     

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS

Objectives:To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).Methods:This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 μm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v).Results:The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r²>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27).Conclusion:This study showed that the gender factor might play a crucial role in nicotine metabolism.     

Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients comorbidly affected by Type 2 diabetes

The mortality of coronavirus disease 2019 (COVID-19) disease is very high among the elderly or individuals having comorbidities such as obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes the metagenomic features in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients with or without type 2 diabetes, to identify the microbial interactions associated with its fatal consequences.This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2-infected diabetic and nondiabetic patients with controls adjusted for age and gender. The metagenomics based on next-generation sequencing was performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. All three groups possessed significant bacterial diversity and dissimilarity indexes (p < 0.05). Spearman's correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r = 0.6–1.0, p < 0.05), and 109 positive correlations between normal flora and probiotic bacteria (r > 0.6, p < 0.05). The SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and secondary infection-causing bacteria (p < 0.05) with a simultaneous decrease of normal flora (p < 0.05). The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19-infected diabetic patients, although a few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those comorbid patients.