Serological Response to COVID-19 and Its Association With Measles-Rubella (MR)-Containing Vaccines.

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.

Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia.

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.

Efficacy of Oral vs. Intravenous Calcium Supplementation for Continuation Therapy in Hypocalcemic Seizures: A Randomized, Controlled Trial.

OBJECTIVE: To evaluate efficacy of oral vs. intravenous calcium supplementation for continuation therapy in hypocalcemic seizures. METHODS: Sixty children between 1 mo and 5 y presenting with hypocalcemic seizures without any other underlying febrile, chronic systemic disease, or acute neurological illness were included. Participants were randomized to receive either intravenous (IV) 10% calcium gluconate (n = 30) or oral elemental calcium (n = 30) for 48 h following initial seizure control with intravenous calcium. RESULTS: Seizures recurred in 3 (10%) children in IV group as compared to 4 (13.3%) in oral calcium group (p = 0.278) within 48 h. Serum calcium levels achieved in the two treatment groups at 24 h [7.96 (1.32) vs. 8.23 (1.58) mg/dL; p = 0.476] and 48 h [8.5 (1.01) vs. 8.63 (1.39) mg/dL; p = 0.681] were comparable. CONCLUSION: Oral calcium may be as efficacious as intravenous calcium during continuation phase of treating hypocalcemic seizures; however, further studies are needed for definite recommendations. TRIAL REGISTRATION: Trial Registration number: CTRI/2017/12/011042.

Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia.

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.

Prevalence and predictors of hypocalcaemia in severe acute malnutrition.

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.

Cardiac autonomic tone, plasma BDNF levels and paroxetine response in newly diagnosed patients of generalised anxiety disorder.

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.Key messageGAD 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.

Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis.

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.

Association of organochlorine pesticides with the mRNA expression of tumour necrosis factor-alpha (TNF-α) & cyclooxygenase-2 (COX-2) genes in idiopathic preterm birth.

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 ß-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, p0 =0.001), p'p'-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, p0 =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. l0 inear positive correlations were observed between period of gestation (POG) and ΔCt 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.

Profile of oxidative stress in response to treatment for type 1 leprosy reaction.

OBJECTIVE: To measure oxidative stress in Type 1 leprosy reaction, and to document the effect of anti-leprosy multidrug therapy (MDT) and anti-reaction drugs on measures of oxidative stress. MATERIALS AND METHODS: A prospective study was carried out at a teaching hospital involving consecutive patients with Type 1 reaction. MDA (malondialdehyde), FRAP (ferric reducing ability of plasma) and GSH (reduced glutathione) were measured in venous blood samples as measures of oxidative stress and compared at inclusion, after 4 weeks of initial therapy (following standard guidelines including MDT, NSAIDS, and systemic steroids), and 4 weeks after clinical remission. RESULTS: The final study cohort included 40 patients with Type 1 reaction (different treatment arms) after excluding for confounding factors such as prior treatment, smoking, NSAID use or concurrent illness requiring therapy. Measures of lipid derived oxidative stress assessed by MDA showed a significant rise with 4 weeks of therapy and a trend towards decline after clinical resolution. In contrast, the other two measures of anti-oxidants namely GSH and FRAP, showed a significant decrease (P < 0.05) at 4 weeks of treatment followed by a significant increase after 4 weeks of clinical remission of reaction. CONCLUSION: MDT and anti-reactional treatment is associated with significant increases in FRAP and GSH levels, reflecting a reduction in the oxidative stress in patients treated for Type 1 reaction. However, lipid peroxidation as measured by MDA is only partially controlled with treatment.

Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: role of GSTM1/GSTT1 polymorphism.

Chronic kidney disease (CKD) of unknown etiology represents about 16% of CKD patients in Indian subcontinents and 10% worldwide. The aetiology of CKD of unknown etiology remains unclear though epidemiological studies indicate the involvement of the environmental toxins. Organochlorine pesticides (OCPs) have been detected in general population in India. It is possible that polymorphism of xenobiotic metabolizing enzymes (XMEs) may play an important role in this process. In this we intend to find out blood levels of OCPs in CKD patients of unknown etiology and to evaluate the consequence of glutathione S-transferase (GST) gene polymorphism on the same. We have assessed 270 CKD patients and 270 age-sex-matched healthy controls for this study. The blood OCP levels were analyzed by gas chromatograph. GSTM1, GSTT1 genotyping were carried out by multiplex PCR. Blood levels of HCH, endosulfan and total pesticides were significantly higher in CKD patients and negatively correlated with eGFR. The combined frequency of GSTM1(-)/GSTT1(-) genotype increased the risk of CKD by 1.8-fold as compared to healthy controls. To find out the dependence of blood OCPs level on genotype, we carried out logistic regression analysis and results revealed that GSTM1(-)/GSTT1(-) genotype associated significantly with a number of OCPs namely γ-HCH, p,p'-DDT and total pesticides. Polymorphism of XMEs not only increased accumulation of pesticides but also aggravates kidney dysfunction as evident from significant decrease in eGFR.

Evaluation of therapeutic efficacy of Majoon Suranjan, a Unani formulation, in the treatment of rheumatoid arthritis: an experimental study.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Allopathic treatments for RA have various side-effects and limitations. Majoon Suranjan (MS) is a polyherbal Unani formulation used to treat RA. Although it is widely used, evidence-based toxicity and efficacy data are not available. The present study was designed to assess the safety and therapeutic efficacy of MS in experimental animals. Acute (14 days) and long-term (90 days) toxicity studies were carried out at three doses of MS, i.e. 440, 880 and 1760 mg/kg body weight in male and female Wistar rats. Arthritis was induced in male rats by immunization with bovine collagen type II and they were treated with vehicle, methotrexate (0.25 mg/kg body weight, intraperitoneal once weekly) and MS (880 mg/kg body weight, orally, daily) for 20 days. Serum rheumatoid factor, anticyclic citrullinated peptide antibody, antinuclear antibody and C-reactive protein (CRP) were estimated. None of the rats exhibited overt toxicity or mortality and MS was found to be safe at the tested doses. No abnormal findings were observed in haematological and biochemical parameters, necropsy and histopathology at therapeutic effective dose. MS significantly inhibited the footpad swelling in arthritic rats while serum autoantibodies and CRP levels were significantly decreased. The present study demonstrates that at therapeutic doses, the Unani medicine, MS is relatively safe. Furthermore, MS was found to be effective in decreasing the biomarkers of RA, thus providing scientific evidence in support of its traditional use in the treatment of RA.

Genetic polymorphisms in Cytochrome P 4501B1 and susceptibility to idiopathic preterm labor in North Indian population.

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.

Association of CYP1A1 gene polymorphism with chronic kidney disease: a case control study.

CYP1A1 is an important xenobiotic metabolizing enzyme, present in liver and kidney. Expression of CYP1A1 enzyme increases manifold when kidney cells are exposed to nephrotoxins/chemicals leading to oxidative stress-induced cell damage. To study the association of CYP1A1 gene polymorphism in patients of chronic kidney disease with unknown etiology (CKDU), we recruited 334 CKDU patients and 334 age and sex matched healthy controls. CYP1A1*2A and *2C polymorphisms were studied by PCR-RFLP and allele specific-PCR respectively. Subjects carrying at least one mutant allele of CYP1A1*2A (TC, CC) and *2C (AG, GG) were shown to be associated with 1.4-2-fold increased risk of CKDU. Also, genotypic combinations of hetero-/homozygous mutants of CYP1A1*2A (TC, CC) with hetero-/homozygous mutant genotypes of CYP1A1*2C (AG, GG) i.e. TC/AG (p<0.01), TC/GG (p<0.05), CC/AG (p<0.05) and CC/GG (p<0.01) were associated with CKDU with an odd ratio ranging 1.8-3.3 times approximately. This study demonstrates association of CYP1A1 polymorphisms with CKDU.

Gene-environment interaction in preterm delivery with special reference to organochlorine pesticides.

We investigated the association between glutathione S-transferases mu1 (GSTM1), theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs) level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected at the time of delivery/after delivery. Women occupationally exposed to OCPs and other high-risk factors such as anemia, hypertension and dietary habit were excluded. The OCP levels were estimated by gas chromatography, and polymorphic analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and PCR-restriction fragment length polymorphism, respectively. The frequency of GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the controls. Significantly high levels of α-hexachlorocyclohexane (HCH), γ-HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane and p'p'-DDE were found in the cord blood of PTD cases compared with the controls. A significant association was seen between ß-HCH and GSTM1 genotype when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and period of gestation (POG) was ascertained. A significant reduction in POG was observed. Similarly, cord blood dieldrin levels were significantly associated with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that higher levels of OCPs in pregnant women may be associated with increased risk of 'idiopathic' PTD. Furthermore, this study shows that the interaction between high OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the risk of PTD, thus providing evidence for a gene-environment interaction in pregnant women.

Therapeutic effect of yoga in patients with hypertension with reference to GST gene polymorphism.

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.

A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India.

OBJECTIVE: To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post-herpetic neuralgia (PHN). METHODS: The study was a prospective, single-blind, non-responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non-responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non-responder group. The primary endpoints were measured using a numerical rating scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. RESULTS: Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non-responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL-BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non-responders. Significant improvement in pain intensity scores and QOL in non-responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. CONCLUSIONS: Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non-responders.

Gene environment interaction in preterm delivery with special reference to organochlorine pesticide: a case control study.

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, ß-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.

Quinalphos induced oxidative stress and histoarcheitectural alterations in adult male albino rats.

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, 2.6 mg/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.

A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides.

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,ß,γ-HCH and p,p'-DDT were found in maternal blood and significantly higher levels of ß 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 ß-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.

CYP2D6*4 polymorphism, tramadol treatment and its clinical impact in patients with postherpetic neuralgia.

AIM: The aim of this study was to investigate the associations between the CYP2D6*4 polymorphism, interindividual differences in CYP2D6 activity and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. PATIENTS & METHODS: The study comprised 158 patients (including 78 nonresponders and 80 responders) with PHN who were undergoing analgesic treatment at the Pain Clinic in the Out Patient Department of the University College of Medical Sciences, Guru Teg Bahadur Hospital (New Delhi, India). The numerical rating scale scores were measured at the resting and movement stages; Neuropathic Pain Symptom Inventory scores were evaluated by the treating physician. WHO-brief questionnaire scores for quality of life and adverse drug effects during the time of study were recorded. All samples were analyzed for the CYP2D6*4 polymorphism using the PCR-restriction fragmentation length polymorphism method. RESULTS: The genotype distribution did not vary significantly among different age groups in nonresponders and responders. The CYP2D6*4 polymorphism was significantly associated with lower Neuropathic Pain Symptom Inventory (burning, squeezing stabbing and pressure) scores. The quality-of-life (sociological, psychological and environmental domains) scores correlated with CYP2D6*4 and showed significant results (p < 0.05) using a generalized linear model. No association was found between the physiological domain compared with the CYP2D6*4 allele (p > 0.05). In addition, the homozygous mutated CYP2D6*4 allele was not related to adverse effects of analgesic therapy. CONCLUSION: The CYP2D6*4 polymorphism may not be a predictor for treatment outcome of patients with PHN receiving tramadol. However, further investigation is required to confirm these findings in a larger sample size.