PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis.Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed.Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy.Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

Risk Factors of Incident Kidney Stones in Indian Adults: A Hospital-Based Cross-Sectional Study.

Background The diverse manifestations of urolithiasis provide very interesting epidemiological data. This has prompted various studies to look into the etiopathogenesis of renal stones, which is believed to be multifactorial, both exogenous and endogenous. VDR Fok1 is a risk factor for renal stone formation and could cause the formation of renal stones through the mechanism of crystal induction and crystallization in the urine. While a few recent studies have shown the role of heavy metals like cadmium and lead in the formation of renal stones, the current knowledge is still insufficient. Methods This case-control prospective study was conducted in Guru Teg Bahadur (GTB) Hospital, a tertiary care facility in Delhi with 30 cases and 30 controls. Patients visiting the department of surgery between November 2011 and April 2013 were enrolled in the study. Cases were defined as patients with renal stones diagnosed on the basis of history and radiological investigations. Controls were selected from the patients admitted to the department of surgery for reasons other than renal stones. The study protocol was approved by the Institutional Ethical Committee of the University College of Medical Sciences, GTB Hospital, Delhi. Written informed consent was obtained from all patients. A structured questionnaire was used to collect data. Metal levels were analyzed by an atomic absorption spectrophotometer (Shimadzu Flame AA-680, Shimadzu Corp., Kyoto, Japan) at Delhi University. The vitamin D receptor gene was measured using genomic DNA. Horizontal agarose gel electrophoresis was used for the quantification of the genomic DNA. Results There were 30 cases and 30 controls in the study. Stress was more prevalent among cases (63%) compared to controls (36%). Nearly 83% of cases had the ff allele of the Vitamin D receptor gene compared to 46% of controls. The median arsenic and lead levels were higher among cases compared to controls. In the unadjusted model of logistic regression, we found stressed patients had three times higher odds of developing renal stones compared to non-stressed patients (OR (95% CI): 2.98 (1.04-8.52); p=0.04). Similarly, patients with higher blood concentrations of arsenic and lead had higher odds of developing renal stones compared to those with lower concentrations.  Conclusions There was a definitive role of heavy metals, including lead, cadmium, and arsenic, seen with renal stones. A significant association was seen between the ff allele of VDR polymorphism (Fok1 enzymes) and patients with renal stones. Other parameters, including male and stress factors, seem to have an important role in renal stone formation.

Genetic Expression of CYP2B6 Gene in Phenobarbitone Responder and Non- responder Neonates.

Quantitative real-time polymerase chain reaction for identifying CYP2B6 gene expression was done on blood samples of 30 phenobarbitone responder and 30 non-responder neonates with seizures. CYP2B6 was observed to be significantly down regulated among phenobarbitone non-responders as compared to phenobarbitone responders (Mean (SD) DCt 17.97 (1.19) vs 15.40 (1.83); P<0.001).

Gut microbiota: a non-target victim of pesticide-induced toxicity.

The human gut microbiota can be potentially disrupted due to exposure of various environmental contaminants, including pesticides. These contaminants enter into non-target species in multiple ways and cause potential health risks. The gut microbiota-derived metabolites have a significant role in maintaining the host's health by regulating metabolic homeostasis. An imbalance in this homeostasis can result in the development of various diseases and their pathogenesis. Pesticides have hazardous effects on the host's gut microbiota, which is evident in a few recent studies. Therefore, there is an urgent need to explore the effect of pesticide on gut microbiota-mediated metabolic changes in the host, which may provide a better understanding of pesticide-induced toxicity. The present review summarizes the pesticide-induced effects on gut microbiota, which in turn, induces changes in the release of their secondary metabolites that could lead to various host health effects.

Silibinin suppresses TGFß2-induced lens epithelial cell migration and epithelial-mesenchymal transition.

Growth factor-induced migration of lens epithelial cell (LEC) toward the posterior of lens capsule bag and their epithelial-mesenchymal transition (EMT) is the key process involved in the pathogenesis of posterior capsular opacification (PCO). Silibinin, a natural flavonolignan, confers therapeutic effects to different cells by regulation of signalling pathways; however, its role in the prevention of migration and EMT of LECs is yet to be analysed. In this study, the inhibitory capabilities of silibinin on migration and EMT were analysed in response to TGFß2 stimulation in HLE B-3 cells. The anti-migratory effect of silibinin was analysed using wound healing assay. Transcriptional and translational expression of genes related to LEC migration, EMT, and transcription factors related to EMT were studied by quantitative real-time PCR and Western blotting. Immunofluorescence analysis was utilized to study the localization of fibronectin. Silibinin reduced the viability of LECs in a concentration-dependent manner and inhibited the wound healing capacity of LECs induced by TGFß2. Silibinin also suppressed alteration in the EMT-related markers such as cytoskeletal proteins, cell adhesion markers, extracellular matrix molecules, and transcription factors. Analysis of downstream signalling revealed that treatment with silibinin decreased phosphorylated Akt (Ser473, Thr308), PDK1 (Ser241), PTEN (Ser380), c-Raf (Ser259), and GSK3ß (Ser9) in TGFß-stimulated cells. The effect of silibinin treatment on phosphorylated Akt resembled that of the PI3K inhibitor LY294002. Our results suggest that silibinin can suppress LEC migration and EMT, which involves the inactivation of the PI3K-Akt signalling pathway. Silibinin might be a good candidate for PCO prevention; however, functional evaluation of silibinin using in vivo models is a pre-requisite.

Role of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases.

BACKGROUND: AMP-activated protein kinase (AMPK) plays a precise role as a master regulator of cellular energy homeostasis. AMPK is activated in response to the signalling cues that exhaust cellular ATP levels such as hypoxia, ischaemia, glucose depletion and heat shock. As a central regulator of both lipid and glucose metabolism, AMPK is considered to be a potential therapeutic target for the treatment of various diseases, including eye disorders. OBJECTIVE: To review all the shreds of evidence concerning the role of the AMPK signalling pathway in the pathogenesis of ocular diseases. METHOD: Scientific data search and review of available information evaluating the influence of AMPK signalling on ocular diseases. RESULTS: Review highlights the significance of AMPK signalling in the aetiopathogenesis of ocular diseases, including cataract, glaucoma, diabetic retinopathy, retinoblastoma, age-related macular degeneration, corneal diseases, etc. The review also provides the information on the AMPK-associated pathways with reference to ocular disease, which includes mitochondrial biogenesis, autophagy and regulation of inflammatory response. CONCLUSION: The study concludes the role of AMPK in ocular diseases. There is growing interest in the therapeutic utilization of the AMPK pathway for ocular disease treatment. Furthermore, inhibition of AMPK signalling might represent more pertinent strategy than AMPK activation for ocular disease treatment. Such information will guide the development of more effective AMPK modulators for ocular diseases.[Formula: see text].

Modulation of signal transduction gene expression following pulsed radiofrequency in dorsal root ganglia and pregabalin therapy.

Introduction: A randomized controlled study was conducted to assess modulation of signal transduction genes (PKA, PKC and ERK) following integrated multimodal approach encompassing pulsed radiofrequency treatment (PRF) of dorsal root ganglion and pregabalin in thoracic postherpetic neuralgia (PHN). Clinical variables such as pain intensity and quality of life were also explored. Material & methods: A total of 40 Patients of PHN were recruited. 20 patients randomly assigned to each of the two groups, group PP administered PRF with pregabalin and group SP administered pregabalin alone. Results: Significant downregulation of PKA and ERK observed in group PP at end of 10th week (p < 0.05). A significantly positive correlation demonstrated between Visual analog scale scores and signal transduction genes expression in PHN patients. Conclusion: Downregulation of all three signal transduction genes was observed following the integrated multimodal approach; however, significant downregulation was observed with PKA and ERK only. A positive correlation observed between signal transduction gene expression and visual analog scale scores signify their role in the pathogenesis of PHN.

People who had nerve pain after recovering from a herpes attack (postherpetic neuralgia) were treated with pulsed radiofrequency (PRF) treatment of the dorsal root ganglion, which involves stimulating a nerve cluster at the base of the spine with radio waves, along with oral pregabalin therapy, or with pregabalin alone. Certain pain genes such PKA, PKC and ERK were found to be suppressed after the combined treatment with PRF and pregabalin. The suppression of these genes was also associated with the self-reported pain scores of the participants in the study.

Adipose Tissue Levels of DDT as Risk Factor for Obesity and Type 2 Diabetes Mellitus.

BACKGROUND: Exposure to dichlorodiphenyltrichloroethane (DDT), a potent lipophilic organochlorine pesticide, has long been linked as a risk factor for type 2 diabetes mellitus (T2DM). However, its presence in the adipose tissues of the T2DM subjects has not been explored in the Indian population, where this long-banned pesticide is still in use. The present study was conducted to evaluate the possible association of DDT and its metabolites in obese and non-obese T2DM subjects. METHODS: Subjects with normal glucose tolerance (n = 50) and T2DM (n = 50) were divided into equal numbers in obese and non-obese groups. Their plasma glucose levels, HbA1c, and lipid profile were measured. The adipose tissues were collected intraoperatively, and DDT and its metabolites were measured using a gas chromatograph equipped with an electron capture detector. RESULTS: Obese subjects, irrespective of their glycemic status, and T2DM subjects had higher concentrations of DDT. p, p' DDT was found to increase the odds for diabetes, and o, p' DDT for central obesity. p, p' DDD was also strongly correlated with central obesity, glycemic parameters, and triglycerides. CONCLUSION: The excess deposition of p, p' DDD, o, p' DDT, and p, p' DDT in obese subjects may proceed to T2DM by disrupting triglycerides and glycemic parameters.

Modulation of the Extracellular Signal-Regulated Protein Kinase and Tissue Inhibitors of Matrix Metalloproteases-1 Gene in Chronic Neuropathic Pain.

OBJECTIVES: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). MATERIALS AND METHODS: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. RESULTS: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. CONCLUSION: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.

Level of Organochlorine Pesticide in Prediabetic and Newly Diagnosed Diabetes Mellitus Patients with Varying Degree of Glucose Intolerance and Insulin Resistance among North Indian Population.

BACKGROUND: Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of ß-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population. METHODS: Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector. RESULTS: Significantly higher levels of ß-hexachlorocyclohexane (HCH), dieldrin, and p,p'-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with ß-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of ß-HCH, dieldrin, and p,p'-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that ß-HCH, dieldrin, and p,p'-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m2); ß-HCH and p,p'-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2. CONCLUSION: The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.

Organochlorine pesticides induce inflammation, ROS production, and DNA damage in human epithelial ovary cells: An in vitro study.

Although the etiology of ovarian cancer is not clear, certain factors are implicated in this disease, such as ovulation, gonadotropic and steroid hormones, growth factors, cytokines, environmental agents, etc. Epidemiological studies have proven environmental exposure to pesticides with an increased risk of Epithelial Ovarian Cancer (EOC); however, the molecular mechanism underlying the carcinogenic effects of pesticides in human ovary remains poorly understood. The present study aimed to study the pro-inflammatory response of organochlorine pesticides (OCPs) namely ß-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene (DDE) and Dieldrin following exposure to human ovary surface epithelial cells (HOSE) for risk prediction of epithelial ovarian cancer. We found high level of Reactive oxygen species (ROS) production and DNA damage along with up-regulation of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, nuclear factor kappa B (NF-kB) and cyclooxygenase (COX)-2 expression in OCPs treated HOSE cells compared to control (DMSO). The result of the present study suggests that ß-HCH, DDE, and Dieldrin exposure induce ROS and pro-inflammatory response as well as DNA damage in HOSE cells. These various results show that OCPs may account for the neoplastic transformation of HOSE cells in the ovary.

Organochlorine pesticide exposure as a risk factor for breast cancer in young Indian women: A case-control study.

BACKGROUND: Incidence rates of breast cancer are showing an increasing trend in young women (≤40 years) in India. Risk for breast cancer in this age group can be attributed only partially to various known risk factors. Environmental exposure to organochlorine (OC) compounds has been identified as a potential risk factor. However, the possible role of OC compounds in increasing breast cancer risk in young women has not been explored. This case-control study was planned with the objectives to assess the serum levels of OC compound in a North Indian population of young women. MATERIALS AND METHODS: Forty-two patients of breast cancer ≤ 40 years age and 42 age-matched controls were evaluated for exposure to OC compounds by performing assays in blood samples for pesticides such as dichlorodiphenyltrichloroethane (DDT) and its metabolites DDD and DDE; dieldrin; aldrin; methoxychlor, heptachlor; α-endosulfan; ß-endosulfan; and hexachlorocyclohexane and its isomers (α, ß, and γ). RESULTS: Young women with breast cancer were found to have significantly higher serum levels of all the OC compounds except aldrin, p, p' DDT, and methoxychlor. CONCLUSIONS: Exposure to OC pesticides could be an important modifiable risk factor for breast cancer, especially in younger women.

High Resolution Based Quantitative Determination of Methylation Status of CDH1 and VIM Gene in Epithelial Ovarian Cancer.

BACKGROUND: DNA promoter methylation is widely explored epigenetic phenomena, known to effect gene expression and further perturbation in cellular homeostasis. Myriad of studies have leveraged promoter methylation and its potential as biomarker for various types of cancer. Aim of present study is to investigate promoter methylation of CDH1 and VIM gene and etiology of epithelial ovarian cancer (EOC). METHODS: Most of previous studies were qualitative; we have quantitatively assessed methylation levels in 50 EOC cases and control each through high recognition melt (HRM) technique. RESULTS: At 10 % cutoff for CDH1 94% of EOC cases were found to be methylated with mean methylation of 45±13.8, whereas for control mean methylation was found to be 7.3±3.7 amongst 16 % methylation positive control samples. For VIM methylation was detected in 96% of cases with mean of 50.44±11.7 in EOC and in 12% methylation positive samples for control mean methylation was 6.24±4.3. CONCLUSION: In short HRM based DNA methylation can serve as a robust and sensitive diagnostic method for promoter methylation detection and as a biomarker for early epithelial ovarian cancer detection.

Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism.

BACKGROUND: Pesticides are major xenobiotic compounds and environmental pollutants, which are able to alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome project, genetic variations (polymorphism) become an integral part of drug development due to their influence on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions collectively. OBJECTIVE: To review all the evidence concerning the effect of environmental exposure on drug metabolism with reference to pharmacogenomics. METHODS: Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics studies were undertaken to evaluate the influence of environmental contaminants on drug metabolism. RESULTS: Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters disease susceptibility as well as the progression of disease under the influence of various environmental contaminants at various levels. CONCLUSION: Individual specific drug response may be attributed to a large variety of factors alone or in combination ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).

Delineating Potential Transcriptomic Association with Organochlorine Pesticides in the Etiology of Epithelial Ovarian Cancer.

BACKGROUND: Recent studies have shown that there is an increased risk of Epithelial Ovarian Cancer (EOC) with Organochlorine Pesticides (OCPs). However, the alteration in the gene expression profile has not been explored so far. The goal of the present study is to understand the probable molecular mechanism of OCPs toxicity towards discovery of dysregulation of signaling pathway associated with differential gene expression and candidate transcriptomic set of markers in the pathophysiology of EOC in OCPs exposed population. METHODS: The OCP levels were estimated by gas chromatography and whole genome differential expression study was carried out using expression microarray and candidate genes were validated using Real time RT-PCR. RESULTS: Significant level of OCP residues such as ß-hexachlorocyclohexane (ß-HCH), Heptachlor, Heptachlor epoxide B (HTEB), dichlorodiphenyldichloroethylene (p'p'-DDE) and endosulfan-I was found between healthy and EOC patients. The transcriptome profile of several genes revealed regulation of various important cellular processes such as metabolism, inflammation, cytoskeleton dysregulation of TGF and WNT pathway in EOC cases with high OCPs. CONCLUSION: This study provides the first evidence showing that differentially expressed genes and dysregulation of signaling pathways might be associated with significant level of OCPs exposure in ovary tissue of epithelial ovarian cancer patients. Moreover, significant correlation of these genes with OCPs revealed that OCPs exposure played vital role in dysregulation of related pathways in the etiology of EOC.

Assessment of urinary cotinine levels in women with gynecological complaints at a tertiary care hospital: A pilot study.

Gynecological effects due to smokeless tobacco exposure are not well studied. This cross-sectional study was undertaken with the objective to evaluate the urinary cotinine levels in women of reproductive age with gynecological complaints. The study was conducted in 2015 at the outpatient clinic of the Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi. A total of 192 consecutive women presenting with gynecological complaints (pelvic inflammatory disease (PID), infertility, and menstrual abnormality) were recruited. Their demographic details and tobacco exposure were recorded. All of them denied exposure to any form of tobacco. Urinary cotinine level of each participant was measured. The mean urinary cotinine level was 23.60 ± 12.00 ng/ml. PID was the most common gynecological complaint. Women with PID had significantly higher urinary cotinine levels compared to those with menstrual complaints and infertility: 24.9548 (±12.259) ng/ml versus 20.2042 (±10.9248) ng/ml. This study highlights the importance of addressing the issue of secondhand smoke exposure and reproductive morbidities in women.

Association of Lead Levels and Cerebral Palsy.

Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods:Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001). Among children with cerebral palsy, 19 (55.88%) children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children.

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.

Chronic persistent post-surgical pain following staging laparotomy for carcinoma of ovary and its relationship to signal transduction genes.

BACKGROUND: The present study was undertaken to evaluate the incidence of chronic persistent post-surgical pain (CPPP) and the role of signal transduction genes in patients undergoing staging laparotomy for carcinoma ovary. METHODS: The present observational study was undertaken following institutional ethical committee approval and informed consent from all the participants. A total 21 patients of ASA grade I to III with age 20-70 years, scheduled for elective staging laparotomy for carcinoma ovary were included. Patients were excluded if had other causes of pain, cognitive dysfunction or chronic neurological disorders. Statistical analysis of pool data was done using SPSS version-17. For various scales like GPE, PDQ, NPSI, the visual analogue scale (VAS), global perceived effect (GPE), the pain DETECT questionnaire (PDQ), and neuropathic pain symptoms inventory (NPSI), one factor repaeted measure ANOVA applied with simple contrast with baseline as on post-operative day 1 (considered as reference and compared with subsequent time-interval), and the P values were adjusted according to "Bonferroni adjustments". In patients with CPPP, the Δct values of mRNA expressions of genes at the end of postoperative day 90 were compared with the baseline control values by one factor repeated ANOVA. P value < 0.005 significant. RESULTS: The present study demonstrates 38.1% (8 out of 21 patients) incidence of CPPP. The functional status and quality of life as were observed to be significantly diminished in all patients with chronic pain. An up-regulation in the mRNA expression of signal transduction and a positive correlation was noted between the mRNA expression of signal transduction genes and VAS score in all patients with CPPP at the end of postoperative day 90. CONCLUSIONS: The reported incidence of CPPP in patients with carcinoma ovary was 38.1%. An up-regulation and positive correlation between mRNA expression of signal transduction genes and VAS score depicts its potential role in the pathogenesis of CPPP.