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Abstract: Cocaine is a popular drug of abuse and despite impressive advances in the understanding of its physiological, pharmacological, and toxic effects, its mechanism of immunosuppression at the cellular level [...]

Objective: To determine the prevalence and predictors of hypocalcaemia in under-five children (1-59 months) hospitalised with severe acute malnutrition (SAM).Design: A cross-sectional study was designed to determine the prevalence of hypocalcaemia among children hospitalised with SAM. Serum Ca and 25-hydroxycholecalciferol (25-(OH)D) were estimated. Hypocalcaemia was defined as serum Ca (albumin-adjusted) <2·12 mmol/l. To identify the clinical predictors of hypocalcaemia, a logistic regression model was constructed taking hypocalcaemia as a dependent variable, and sociodemographic and clinical variables as independent variables.Setting: A tertiary care hospital in Delhi, between November 2017 and April 2019.Participants: One-hundred and fifty children (1-59 months) hospitalised with SAM were enrolled.Results: Hypocalcaemia was documented in thirty-nine (26 %) children hospitalised with SAM, the prevalence being comparable between children aged <6 months (11/41, 26·8 %) and those between 6 and 59 months (28/109, 25·7 %) (P = 0·887). Vitamin D deficiency (serum 25-(OH)D <30 nmol/l) and clinical rickets were observed in ninety-eight (65·3 %) and sixty-three (42 %) children, respectively. Hypocalcaemia occurred more frequently in severely malnourished children with clinical rickets (OR 6·6, 95 % CI 2·54, 17·15, P < 0·001), abdominal distension (OR 4·5, 95 % CI 1·39, 14·54, P = 0·012) and sepsis (OR 2·6, 95 % CI 1·00, 6·57, P = 0·050).Conclusion: Rickets and hypocalcaemia are common in children with SAM. Routine supplementation of vitamin D should be considered for severely malnourished children. Ca may be empirically prescribed to severely malnourished children with clinical rickets, abdominal distension and/or sepsis. [ABSTRACT FROM AUTHOR]

Objective: The study examined the effect on cardiac autonomic tone via heart rate variability (HRV), brain derived neurotrophic factor (BDNF) in newly diagnosed generalised anxiety disorder (GAD) cases with paroxetine-controlled release (PX) CR intervention. Methods: Fifty GAD cases using DSM-5 criteria, matched with healthy controls (HC) were assessed with clinical measures (Hamilton Anxiety Scale (HAM-A), Clinical Global Impression- Severity Scale (CGI-Severity), General Health Questionnaire -12 (GHQ-12), HRV, plasma BDNF levels initially and 6 weeks postintervention with paroxetine CR. Results: HRV parameters were significantly lower in GAD vs HC at baseline for standard deviation of normal to normal intervals (SDNN) and proportion of differences in consecutive NN intervals that are longer than 50 ms (pNN50). Significantly higher plasma BDNF levels were noted between HC versus GAD at baseline. Postintervention HAM-A, CGI scores, GHQ-12 item scores showed significant reduction. Significant differences also noted in square root of mean squared difference of successive NN intervals (RMSSD), (SDNN), pNN50 and in plasma BDNF levels after intervention within GAD group. Significant negative correlation observed between HAM-A scores and SDNN parameter after taking PX CR in GAD. Conclusion: GAD showed cardiac autonomic dysfunction, lowered plasma BDNF levels and their improvement with paroxetine CR. GAD is associated with significantly lower HRV, suggestive of cardiac autonomic dysfunction and lowered plasma BDNF levels, an indicator of stress. Therapeutic intervention with Paroxetine in GAD patients showed clinically significant improvement reflecting restoration of the cardiac autonomic tone and BDNF levels, thus implying their role as potential biomarkers. [ABSTRACT FROM AUTHOR]

Background: Hypertension, a chronic medical condition of increased blood pressure, is a serious public health problem. Environmental and genetic risk factors are known to predispose to hypertension. The present study was designed to investigate the association of glutathione S-transferase ( GST) gene polymorphism with oxidative stress in hypertensive patients and the possible beneficial effect of yoga on them. Materials and methods: Sixty (60) hypertensive individuals, between 30 and 60 years of age, were divided into two groups of 30 each. The yoga group was subjected to 50-60 minutes of yogic practices daily for 42 days, while the control group included the remaining 30 age- and sex-matched hypertensive individuals. GST gene polymorphism was analyzed using multiple allele specific polymerase chain reaction, and oxidative stress parameters were assessed biochemically. Results: Assessment of blood pressure showed a statistically significant though modest reduction ( p<0.05) in the yoga group as compared to the control group. Malondialdehyde was observed to be significantly low ( p<0.05), while antioxidant capacity in the form of GST showed an increasing trend and ferric-reducing ability of plasma was significantly increased ( p<0.05) in the subjects who practiced yoga. Conclusions: In conclusion, yoga has been found to decrease blood pressure as well as the levels of oxidative stress in patients with hypertension. [ABSTRACT FROM AUTHOR]

Abstract: Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphorus pesticide which is extensively used in agriculture for controlling insect pests. Except a FAO/WHO report no study has investigated its short-term toxicity with respect to its potential to cause biochemical and histopathological alterations. The present study was designed to identify the effect of TZ at different doses (1.64, 3.2 and 8.2mg/kg) on the oxidative stress parameters in blood as well as organs involved in xenobiotic metabolism (liver and brain) following chronic exposure for 90days. Moreover, the study also delineates the effect of TZ on the histo-architecture of these organs. The results indicated a dose dependent induction (p <0.001) of oxidative stress, as evident by increased malondialdehyde (MDA) level and compromised antioxidant defense including glutathione S transferase (GST) activity, glutathione (GSH) content and ferric reducing ability of plasma (FRAP) in blood, and increased MDA level with concomitantly decreased GSH content in tissues, following chronic exposure to TZ. The ratio of MDA: FRAP in blood was found to be increased following chronic exposure to TZ and may serve as a suitable indicator of severity of oxidative damage. Onset of such biochemical alterations is one of the early adaptive responses to TZ exposure which leads to histopathological alterations in terms of diffuse fatty changes expanding from mid-zonal area to whole lobule in liver. However, increased oxidative stress did not bring any morphological alteration in brain. The present study concludes that induction of oxidative stress, leading to subsequent histopathological alterations in liver, is an important mechanism underlying the TZ induced chronic toxicity. [Copyright &y& Elsevier]

Association of glutathione S-transferase (GST) M1 and T1 deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role of GST deletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into: GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed in GSTM1-/GSTT1- as compared to GSTM1+/GSTT1+ in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion. [ABSTRACT FROM AUTHOR]

Background and Objective: Glutathione S-transferases (GSTs) belong to a family of ubiquitous and multifunctional enzymes that work as one of the endogenous antioxidants in our body. This study was designed to look into the association of GST polymorphism with oxidative stress in both diabetic and nondiabetic chronic kidney disease (CKD). Design and Methods: Three groups of patients (50 in each): diabetics without CKD (DM), diabetic CKD (DM-CKD), and nondiabetic CKD (NDM-CKD) and 50 age- and sex-matched healthy controls were recruited. Genotyping was done for GSTM1 and GSTT1 genes using a multiplex polymerase chain reaction. Serum GST and malondialdehyde (MDA) as a marker of oxidative stress were measured spectrophotometrically. Results: Based on genotyping, subjects were categorized as GSTM1+/GSTT1+, GSTM1−/GSTT1+, GSTM1+/GSTT1−, and GSTM1−/GSTT1−. Serum GST levels were lower among subjects with deletion in one/both GST genes, whereas MDA levels were found to be correspondingly raised. A negative correlation for MDA versus GST levels was observed among genotypes with one/both gene deletions. Presence of GSTM1+/GSTT1− and GSTM1−/GSTT1− was significantly higher among patients with CKD in both diabetics and nondiabetics. Interpretations and Conclusions: GSTM1 and GSTT1 deletions singly or together were associated with lower GST levels and higher oxidative stress in both diabetic and nondiabetic CKD. Interestingly, GSTT1 deletion appears to be associated with both diabetic and nondiabetic CKD irrespective of the GSTM1 status. [ABSTRACT FROM AUTHOR]

The molecular mechanism for noncholinergic toxicity of phosphamidon, an extensively used organophosphate pesticide, is still not clear. The aim of the present study is to find the possible molecular mechanism of this pesticide to induce apoptosis and the role of different drugs for attenuation of such effects. Human peripheral blood mononuclear cells (PBMC) were incubated with increasing concentrations of phosphamidon (0-20 μM) for 6-24 h. The MTT assay reveals that phosphamidon induces cytotoxicity in a dose-dependent manner. Cellular glutathione (GSH) is depleted in a dose-dependent manner from 55% to 70% at concentrations between 10 and 20 μM. The percentage of cells that bind to Annexin-V, which is a representative of cells either undergoing apoptosis or necrosis during 24 h incubation, increases in a dose-dependent manner. Above 5 μM, significant necrosis of cells was observed. DNA fragmentation assay revealed that at low concentration of phosphamidon (1 μM), no appreciable change in DNA fragmentation was seen; however, distinct fragmentation was observed beyond 2.5 μM. Phosphamidon was found to cause significant depletion of GSH, which correlates well with the percentage of cells undergoing apoptosis. An increasing trend in levels of cytochrome c was observed with increasing concentration of phosphamidon, indicating that the apoptotic effect of phosphamidon is mediated through cytochrome c release. Coadministration of the antioxidants N-acetylcysteine and curcumin attenuated phosphamidon-induced apoptosis. This further supports our hypothesis that oxidative stress, as indicated by GSH depletion, results in the induction of apoptosis by release of cytochrome c. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:286-292, 2010; View this article online at . DOI 10.1002/jbt.20337 [ABSTRACT FROM AUTHOR]

A number of studies have focused attention on various biochemical abnormalities evoked due to exposure to organochlorine pesticides (OCPs). The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and assess the levels of different non-enzymatic oxidative stress markers as well as to establish correlation with OCP levels, if any. Thirty women in each group of full-term delivery (FTD; ≥37 weeks of gestation) and preterm delivery (PTD; <37 weeks of gestation) were enrolled in this study. Levels of OCPs like Hexachlorocyclohexane (HCH), endosulfan, p,p′ Dichlorodiphenyldichloroethylene (DDE) and p,p' Dichlorodiphenyltrichloroethane (DDT) were analyzed by gas chromatography. Non-enzymatic oxidative stress was measured by the quantification of malondialhyde (MDA), protein carbonyl, reduced glutathione (GSH) and ferric-reducing ability of plasma (FRAP). MDA and protein carbonyl levels were increased significantly, while the levels of GSH and FRAP were decreased in PTD in comparison to FTD cases. We have observed higher levels of β-HCH and α-endosulfan and increased oxidative stress in PTD than FTD cases. In PTD cases, a significant positive correlation was observed between maternal blood levels of β-HCH and MDA (r = .78), β-HCH and GSH (r = -.65), γ-HCH and MDA (r = .89), γ-HCH and GSH (r = -.74) and α-endosulfan and MDA (r = .54) in PTD cases. We also found significant correlations between cord blood levels of β-HCH and MDA (r = .59), β-HCH and GSH (r = -.69), γ-HCH and MDA (r = .62) and α-endosulfan and MDA (r = .54) in PTD cases. In conclusion, our results suggest that higher levels of some of the OCP residues may be associated with PTD and increased oxidative stress. [ABSTRACT FROM AUTHOR]

Present study investigated whether endosulfan, an organochlorine pesticide is able to deplete glutathione (GSH) and induce apoptosis in human peripheral blood mononuclear cells (PBMC) in vitro. The role of oxidative stress in the induction of apoptosis was also evaluated by the measurement of the GSH level in cell lysate. The protective role of N-acetylcysteine (NAC) on endosulfan-induced apoptosis was also studied. Isolated human PBMC were exposed to increasing concentrations (0-100 µM) of endosulfan (α/β at 70:30 mixture) alone and in combination with NAC (20 µM) up to 24 h. Apoptotic cell death was determined by Annexin-V Cy3.18 binding and DNA fragmentation assays. Cellular GSH level was measured using dithionitrobenzene. Endosulfan at low concentrations, i.e., 5 and 10 µM, did not cause significant death during 6 h/12 h incubation, whereas a concentration-dependent cell death was observed at 24 h. DNA fragmentation analysis revealed no appreciable difference between control cells and 5 µM/10 µM endosulfan treated cells, where only high molecular weight DNA band was observed. Significant ladder formation was observed at higher concentration, which is indicative of apoptotic cell death. Intracellular GSH levels decreased significantly in endosulfan-treated cells in a dose-dependent manner, showing a close correlation between oxidative stress and degree of apoptosis of PBMC. Cotreatment with NAC attenuated GSH depletion as well as apoptosis. Our results provide experimental evidence of involvement of oxidative stress in endosulfan-mediated apoptosis in human PBMC in vitro. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:299-304, 2008; Published online in Wiley InterScience (). DOI 10.1002/jbt.20240 [ABSTRACT FROM AUTHOR]

The study was designed to evaluate the oxidative stress and modulation of anti-oxidant enzymes in 10 accidental argimone oil poisoning cases admitted in a hospital in Delhi, India during a recent outbreak of epidemic dropsy in 1998. Serum malondialdehyde (MDA) level, oxygen free-radical scavenging enzymes such as superoxide dismutase (SOD) and catalase (CAT), and glutathione (GSH) and related enzymes, e.g. glutahione reductase (GR), glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione-S-transferase (GST) in erythrocytes were assayed. The sanguinarine level in serum was measured by high-performance liquid chromatography. The serum MDA level was higher and the GSH level in erythrocytes was lower in argimone oil poisioning cases than those in controls. There was a significant decrease in SOD and GPx activities in erythrocytes of epidemic dropsy cases but no changes were observed in CAT, GR and GST assay. The depletion of GSH in erythrocytes, serum MDA level and clinical severity were dependent on serum sanguinarine level. The results indicate that sanguinarine (argimone oil) poisoning creates an oxidative stress in humans. The oxidative stress and differential modulation of anti-oxidant enzymes by sanguinarine might play a pathogenic role in epidemic dropsy, which suggests the incorporation of anti-oxidant drugs in the treatment protocol of the disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] First report on significant association of CYP1A1 polymorphism with idiopathic CKD. [•] Association of CYP1A1*2A and *2C hetero-/homozygous genotype combination with CKD. [•] First report of its kind on Indian population. [Copyright &y& Elsevier]

Abstract: Objectives: Recurrent miscarriage (RM) is a challenging medical problem because of its unknown pathogenesis and etiology in most of the cases. Recent studies suggest the role of persistent environmental pollutants such as organochlorine pesticides (OCPs) in the etiology of RM. The present study was conducted to investigate possible associations of OCPs in the pathogenesis of RM. Design and methods: Blood OCP levels were analyzed in women with RM (cases) and women with normal full term delivery with live birth (controls) by using a gas chromatograph equipped with an electron capture detector. Results: A statistically significant association (p =0.01) was observed between blood γ-HCH levels and women with recurrent miscarriages. Conclusions: This study suggests that high blood levels of γ-HCH may be associated with risk of RM. [Copyright &y& Elsevier]

Background & objectives: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX- 2) in preterm delivery (PTD) cases. Methods: Maternal blood samples of PTD (n=30) cases and equal number of term delivery (n=30) were collected at the time of labour. Women occupationally exposed to OCPs and other high risk factors such as anaemia, hypertension, bacterial vaginosis, renal and heart disease, diabetes, etc. were excluded. The OCP levels were estimated by gas chromatography, and mRNA expressions of TNF-α and COX-2 genes were analysed using real-time PCR (qPCR). Results: Significantly higher levels of β-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, P=0.001), p'p'-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, P=0.003), and o'p'-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. Linear positive correlations were observed between period of gestation (POG) and ▵ Ct of COX-2 and TNF-α genes. Interpretation & conclusions: Environmental factors such as OCPs may be associated with inflammatory events showing gene-environment interaction in PTB cases. Evaluating the molecular control of inflammation along with gene environment interaction may be used as a model to explore the aetiology of idiopathic PTB cases and may be considered for the prognosis of adverse reproductive outcomes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Presence of OCPs in CKD patients of unknown etiology. [•] Polymorphism of GSTs gene significantly associated with OCPs in CKD. [•] Polymorphism of GSTs and accumulation of pesticides aggravates kidney dysfunction. [•] First report of its kind on Indian population. [Copyright &y& Elsevier]

Abstract: Objective: The etiology of preterm labor (PTL) is still unknown, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We investigated the relation between PTL and polymorphisms in Cytochrome P4501B1 (CYP1B1) gene, which is involved in the metabolism of a wide range of environmental toxins and hormones. Design and methods: Three hundred (n=300) cases of PTL and equal number of subjects of full term labor (FTL), after excluding all the known risk factors for PTL were included in the study. A two step allele specific PCR was performed for polymorphic analysis of CYP1B1 gene. Results: The homozygous variant genotype of CYP1B1*2 (OR=2.97, 95%CI=1.08–8.08, p=0.033) and heterozygous variant of CYP1B1*3 (OR=2.57, 95%CI=1.88–3.63, p=0.001), and CYP1B1*7 (OR=2.59, 95%CI=1.85–3.62, p=0.001) were found to be significantly higher in PTL cases as compared to FTL. Conclusions: The present study demonstrates the possible association of homozygous variant of CYP1B1*2 and heterozygous variant of CYP1B1*3 and CYP1B1*7 genes with the increased risk of PTL. [Copyright &y& Elsevier]

Context • Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Habb-e-Asgand (HEA) is a polyherbal, Unani formulation widely used in the treatment of RA. Traditional systems of medicine or plant-based drugs are an attractive alternative treatment because of their professed efficacy in curing the disease. Medicinal herbs and herbal formulations are generally considered to be safer than the conventional drugs for RA. Unani drugs are known not to produce toxic effects and are presumed to be nontoxic. However, no objective, verifiable data exists to support the claims of nontoxicity and efficacy. Objectives • The present study was designed to evaluate the safety and therapeutic efficacy of HEA in Wistar rats. Setting • The study took place at the University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi, India. Design • Oral toxicity studies--one acute (14 d) and one long-term (90 d)--were carried out using three doses of HEA--57.5, 115, and 230 mg/kg body weight (BWT-)-in both male and female rats. The research team also carried out a study on antirheumatic activity. The team induced arthritis in three groups of male rats using collagen type II (CII), and for 20 d, one group was treated once weekly with saline; a second group was treated once weekly with methotrexate (MTX) at 0.25 mg/kg BWT IP; and a third group was treated daily with HEA at 115 mg/kg BWT orally. A control group received saline but was not induced with RA. Outcome Measures • Rheumatoid factor (RF); anticyclic citrullinated peptide (a-CCP) antibody; antinuclear antibody (ANA); and C-reactive protein (CRP) were measured. Results • The acute and long-term, oral toxicity studies showed that HEA administration did not produce any overt toxicity or mortality and that it was safe at all dose levels tested. No major alterations were observed in hematology, serum biochemistry, necropsy, and histopathology at the therapeutic equivalent dose (ie, 115 mg/kg BWT). HEA administration for 20 d in arthritis-induced rats significantly reduced the levels of autoantibodies and CRP, and the results were comparable with those of MTX, the standard, disease-modifying antirheumatic drug (DMARD). Conclusion • The study's results provided evidence that HEA is not toxic at the therapeutic dose. The antiarthritic activity of HEA may be due to its disease-modifying activities, thus supporting the traditional use of this formulation for treatment of RA. {Altern Ther Health Med. 2013;19(5):52-59.) [ABSTRACT FROM AUTHOR]

Abstract: Quinalphos is a synthetic organophosphate used as a broad spectrum insecticide and acaricide. The present study investigates the effect of three sub-lethal doses (0.52, 1.04, 2.6mg/kg b.wt) of quinalphos for variable durations (15, 30 and 90 days) on oxidative stress and histopathological changes in adult male rats. Quinalphos treatment for 15 and 30 days resulted in a dose dependent significant increase in malondialdehyde (MDA) levels and glutathione-S-transferase (GST) activity together with a concurrent decrease in ferric reducing ability of plasma (FRAP) and glutathione (GSH) content. Quinalphos treatment for 90 days also induced a significant increase in MDA levels and GST activity but the effect was not dose-dependent. Histopathological examination of liver revealed architectural disarray and dilatation of sinusoids, focal fatty changes, accumulation of eosinophils and single cell necrosis with increasing doses. However, spleen and kidney did not show any histological changes. Administration of quinalphos resulted in oxidative stress and free radical induced injury as evidenced by increased lipid peroxidation, decreased FRAP and histopathological changes in liver. [Copyright &y& Elsevier]

Abstract: Objectives: Organochlorine pesticides (OCPs) and oxidative stress are reported to be associated with adverse reproductive outcomes. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous toxins including OCPs. OCPs are endocrine disrupter and prenatal exposure to them may be associated with fetal growth restriction (FGR). The objectives of the present study were (i) to determine the frequencies of polymorphic alleles of GSTM1 and GSTT1 genes in women with idiopathic FGR, (ii) to analyze the maternal and cord blood levels of the OCPs, and (iii) to identify the gene environment interaction that increases the risk of FGR. Study design: Maternal and cord blood samples of 50 FGR cases (birth weight <10 percentile for gestational age as per Lubchenco''s growth chart) and equal number of normal pregnancies who were occupationally non exposed to OCPs and excluding all the known high risk factors such as anemia, hypertension, antiphospholipid antibody syndrome, medical disease, dietary habit, living style, parity, and BMI. The collected samples at the time of delivery/after delivery were analyzed for OCPs levels by gas chromatography and polymorphic analysis for GSTM1/GSTT1 gene using multiplex PCR. Results: Significantly higher levels of α,β,γ-HCH and p,p′-DDT were found in maternal blood and significantly higher levels of β and γ-HCH and p,p′-DDT were found in cord blood of FGR cases as compared to controls. The genotypic distribution of GSTM1/GSTT1 was almost similar in both the groups, but the frequency of GSTM1−/GSTT1− (null) genotype was significantly higher in FGR cases as compared to controls (p <0.05, OR=6.42). When interaction between GSTM1/GSTT1 genes polymorphism-OCPs levels and birth weight (gene–environment interaction) was ascertained, a significant association was seen between β-HCH and GSTM1− genotype with reduction in birth weight of 213g. Conclusion: Higher levels of OCPs in pregnant women may be considered as an important aetiological factor in ‘idiopathic’ FGR. GST polymorphism can influence the relationship between prenatal exposure to pesticides and FGR. The present study provides evidence that polymorphism in xenobiotic metabolising genes may modify the effect of environmental health hazards and increase the risk of FGR. [Copyright &y& Elsevier]

Abstract: The scabicide, lindane induces oxidative stress and immunological alterations. The present study was undertaken to assess the ameliorative effects of antioxidant supplementation in lindane treated scabies patients. Scabies patients were treated with either 1% lindane or 1% lindane along with antioxidant (Lycored or Vitamin-E). Oxidative stress and immunological parameters were evaluated in blood samples and compared with healthy controls. Lindane caused a significant increase in malonedialdehyde (MDA) levels and decrease in reduced glutathione (GSH) and ferric reducing ability of plasma (FRAP), which was attenuated by anti-oxidant therapy. The IL-1α levels were significantly enhanced in scabies patients per se and remained unaffected after lindane/anti-oxidant treatment. The TNF-α and nitroblue tetrazolium (NBT) reduction levels were not significantly different in all the groups. Topical application of lindane induces significant free radical generation and may cause immunological alterations which can be reversed by antioxidant therapy. [Copyright &y& Elsevier]

Abstract: Objective : Oxidative stress and related gene polymorphism may be associated with the etiology of preterm labor (PTL). The present study was designed to investigate association of GSTM1 and GSTT1 gene polymorphisms with PTL and their relationship with oxidative stress markers. Design and methods : Sixty cases of PTL and sixty three subjects of full term labor (FTL) were included in the study. Multiplex PCR was performed for GSTM1 and GSTT1 genes polymorphism and oxidative stress markers were analyzed. Result : MDA and 8-OHdG levels were increased, while GSH was decreased in PTL than FTL subjects. Frequency of GSTM1−/GSTT1−(null) was significantly higher in PTL in comparison to FTL (p =0.028, OR=3.4). Subjects with GSTM1−/GSTT1+, GSTM1+/GSTT1−, GSTM1−/GSTT1− have significant differences of oxidative stress markers as compared to GSTM1+/GSTT1+ genotype. Conclusion : GSTM1−/GSTT1− (null) genotype may be one of the associated genetic factor for the increased risk of PTL. [ABSTRACT FROM AUTHOR]

Abstract: Neurosteroids (NS) are recognized as important modulators of functioning of the nervous system. Lindane, an organochlorine pesticide has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of effects of lindane over cognitive function by progesterone (PROG), pregnenolone sulfate (PREG-S) and 4′-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on a plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL was found for the lindane treated group at weeks 6 and 7 as compared to control (p <0.001). One-week treatment by PREG-S or 4CD antagonized the effect of lindane on SDL. PROG failed to modulate the effect of lindane on SDL. Lindane caused a significant prolongation of TL as compared to control (p <0.001) from second week onwards. One-week administration of PROG, PREG-S or 4CD was unable to reverse this prolongation of TL. Lindane produced a statistically significant increase in the brain MDA levels (p <0.001) and significant decrease in the brain NP-SH levels (p <0.001). Treatment with PREG-S and 4CD attenuated the effect of lindane on MDA (p <0.001) and NP-SH levels. PROG failed to influence oxidative stress induced by lindane. Results of the present study thus show that some NS have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like lindane in the brain. [Copyright &y& Elsevier]

Background and Objectives:  Epidemiological studies suggest that coronavirus disease 2019 (COVID-19) has a less severe disease course and a more favorable prognosis among children. Childhood vaccines and heterologous immunity have been suggested as reasons for this. Additionally, the structural similarity between the measles, rubella, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus particles may affect immune responses. The objective of this study was to compare COVID-19 antibody titers and disease severity between measles-rubella (MR) vaccinated and unvaccinated children. Additionally, we aimed to evaluate and compare the antibody response in recipients of a single dose and two doses of the MR vaccine., Methods:  The study was prospective and comparative and included 90 COVID-19-positive children aged nine months to 12 years. The study was registered under the clinical trials registry of India (CTRI/2021/01/030363). COVID-19 antibody titers were measured at two weeks, six weeks, and 12 weeks, along with the assessment of MR antibody titers. COVID-19 antibody titers and disease severity were compared between MR-vaccinated and MR-unvaccinated children. The comparison of COVID-19 antibody titers between recipients of a single dose and two doses of MR vaccine was also conducted., Results: The results showed significantly higher median COVID-19 antibody titers at all time points during follow-up in the MR-vaccinated group (P<0.05). However, the two groups had no significant difference in the disease severity. Moreover, there was no difference in the antibody titers of MR one dose and two dose recipients., Conclusion: Exposure to even a single dose of MR-containing vaccine enhances the antibody response against COVID-19. However, randomized trials are necessary to further explore this subject., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shrivastava et al.)

Introduction Plasma antioxidant capacity in children receiving chemotherapy decreases due to the effect of the disease and chemotherapy. Increased oxidative stress (OS) predisposes to an increased risk for chemotherapy-related toxicity and febrile neutropenic episodes. Materials and methods We conducted this case-control study in the hematology-oncology unit of the department of pediatrics of a tertiary hospital in Delhi, India, from November 2017 to March 2019 to compare OS between children with acute lymphoblastic leukemia (ALL) and healthy controls. We estimated the trends in OS as measured by the plasma total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) levels at baseline and at the completion of induction I (four weeks), induction II (eight weeks), and induction IIA-consolidation (16 weeks) phases of chemotherapy in children with ALL. We also assessed the change in OS during different phases of initial treatment and studied the association between OS and the hematological toxicity of chemotherapy (determined by the need for blood component therapy and the number of febrile neutropenic episodes) and serum cobalamin and folate levels. Results OS was significantly higher in children with ALL at diagnosis (n=23) compared to controls (n=19). The median (interquartile range (IQR)) TAC levels (mM) were significantly lower (1.21 (1.05-1.26) versus 1.28 (1.26-1.32), P=0.006), and TBARS levels (nmol/mL) were significantly higher (312.0 (216.6-398.0) versus 58.5 (46.2-67.2), P<0.001) in children with ALL at diagnosis compared to controls. OS was highest at the end of the induction I phase (four weeks) despite the patients being in clinical and hematological remission. OS at the completion of intensive chemotherapy (16 weeks) was higher than at diagnosis. A significant correlation was found between serum folate levels and TAC levels at baseline (P=0.03). Serum cobalamin levels, the need for blood component therapy, and the number of febrile neutropenic episodes did not have any association with OS. Conclusion Children with ALL had significantly higher OS compared to controls, indicating that underlying disease affects the oxidative balance unfavorably. Chemotherapy itself increases oxidative stress., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chaudhary et al.)

Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P<0.001]. CSF 8-OH-dG levels at the end of four weeks, eight weeks, and 16 weeks of chemotherapy were [3.96 (2.85-5.44) ng/mL], 1.00 (0.89-1.09), and 3.73 (2.80-4.39) ng/mL, respectively. Out of 23 children with ALL, 12 developed neurotoxicity; the CSF levels of 8-OH-dG in them were only marginally higher compared to those who did not develop neurotoxicity. The CSF 8-OH-dG levels did not show a significant correlation with the number of doses of methotrexate or vincristine received. Conclusion Chemotherapy increases the CNS oxidative stress as measured by CSF 8-OH-dG levels, with the levels being proportional to the intensity of chemotherapy. Children with neurotoxicity had only marginally higher CSF 8-OH-dG levels as compared to children without neurotoxicity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Dewan et al.)

Background: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA., Methods: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment., Results: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis., Conclusion: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To assess the Gene-Environmental interaction between maternal organochlorine pesticides (OCPs) level and CYP17 gene polymorphism with the risk of preterm delivery (PTD)., Materials and Methods: Maternal blood samples of hundred cases (n = 100) of PTD and of equal number of healthy controls were collected at the time of delivery. OCPs levels were estimated by Gas chromatography system equipped with electron capture detector and PCR-RFLP was used for polymorphic analysis of CYP17 gene., Results: Significantly (p < 0.05) higher levels of α-HCH, β-HCH, and γ-HCH were found in maternal blood samples of PTD cases as compared to controls. We did not found any significant difference in the frequency genotype distribution CYP17 gene in PTD cases as compared to controls. When gene environmental interaction between the CYP17 gene polymorphism and OCPs level was considered, a significant interaction was observed between ≥ 50th percentile of γ-HCH and CYP17 A1A1 (wild type) genotype., Conclusions: Higher levels of OCPs along with wild type state of CYP17 gene (A1A1) in women may be considered as an important etiological factor in 'idiopathic' PTD. The present study provides evidence that genetic variation and its interaction with the environmental exposure may increase the risk of PTD.

The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with aconcomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histoarchitectural alterations at sub-chronic doses of triazophos in rats.

Association of diabetic nephropathy (DN) with the deletion of GSTT1 and GSTM1 genes is well reported. Oxidative stress (OS) has also been associated with the development of DN. The present study was conducted to find out, whether these deletions had any contributory role in the development of OS in patients with DN. Pre-dialysis venous blood samples were obtained from 60 patients with diabetic end-stage renal disease (stages 4 and 5). Reduced-glutathione (GSH), glutathione S-transferase (GST) activity and malondialdehyde (MDA) levels were measured for the assessment of OS. Genetic polymorphism analysis of DN patients revealed the following distribution pattern: GSTM1 null 46.7%; GSTT1 null 55%; both null 30% and both positive 28.3%. Patients with both null genotypes were found to have significantly increased levels of MDA and low GST activity as compared to other genotypic groups. Lower GSH levels were observed in all the genotypic groups as compared to both positives. Double deletions involving GSTT1 and GSTM1 may result in decreased GST levels, leading to increased OS as reflected by increased MDA levels. As GST is a multi-functional enzyme involved in xenobiotic metabolism, this double null genotype population has a greater risk of development of DN. Further studies using increased sample size to find out the allelic distribution and their role in the development of DN are in progress.

The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

The protective effect of dietary feeding of Zingiber officinales Rosc. (ginger) against lindane-induced oxidative stress was investigated in male albino rats. Oxidative stress was monitored by estimating the extent of lipid peroxidation, activities of the oxygen free radical (OFR) scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) and the status of the glutathione redox cycle antioxidants. Lindane administration (30 mg/kg bw orally for 4 weeks) was associated with enhanced lipid peroxidation and compromised antioxidant defenses in rats fed a normal diet. Concomitant dietary feeding of ginger (1%w/w) significantly attenuated lindane-induced lipid peroxidation, accompanied by modulation of OFR scavenging enzymes as well as reduced glutathione (GSH) and the GSH dependent enzymes glutathione peroxidase (Gpx), glutathione reductase (GR) and glutathione-S-transferase (GST) in these rats. These findings suggest that a diet containing naturally occurring compounds is effective in exerting protective effects by modulating oxidative stress.

Background & Objectives: Polymorphous light eruption (PMLE) is a photo-induced disease which clinically manifests in the form of pruritic eruptions on sun/light exposed parts. Little is known about lipid peroxidation and free radical scavengers in patients during PMLE. The present study was therefore undertaken to evaluate oxidative stress and levels of antioxidant enzymes in patients of PMLE., Methods: The PMLE was diagnosed clinically by a consultant dermatologist and validated independently by another and through histopathologic findings. Blood samples were collected on day 1 and patients were given oral vitamin E supplementation (400 mg OD) along with topical sunscreen and advice for photo-protection. Samples were collected again after one week. The blood samples were evaluated for lipid peroxidation, oxygen free radical (OFR) scavenging enzymes, glutathione (GSH) and related enzymes such as glutathione reductase (GR), glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione- S-transferase (GST) in erythrocytes and compared with healthy controls., Results: The serum malondialdehyde (MDA) level was higher and GSH level was lower in PMLE cases as compared to controls. There was a significant decrease in superoxide dismutase (SOD) activity while activities of catalase (CAT) and glutathione related enzymes were increased in PMLE cases. Administration of oral vitamin E for one week, along with photoprotection resulted in a significant decrease in MDA levels and activities of all others enzymes except SOD. The GSH was replenished and returned to normal., Interpretation & Conclusion: Oxidative stress and differential modulation of antioxidant enzymes in PMLE might play a pathogenic role in humans, which supports the incorporation of antioxidant drugs in the treatment protocol of the disease.

Effect of subchronic doses of phosphamidon exposure on humoral and cell mediated immune (CMI) responses were studied in male albino rats using SRBC, ovalbumin and KLH as antigens. Humoral immune responses were assessed by estimating antibody titre against antigen and splenic plaque forming cells (PFC) assay. CMI responses were studied by using leucocyte migration inhibition (LMI), macrophage migration inhibition (MMI) and delayed type hypersensitivity (DTH) response. Results obtained in the present study revealed marked suppression of humoral and CMI responses in a dose dependent pattern. Hence, suppression of immune responses by phosphamidon even at subchronic doses is clearly an important aspect for its safety evaluation.

Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation.