Long-Term Persistence of COVID-Induced Hyperglycemia: A Cohort Study.

Although the short-term mortality of patients with COVID-19 infection and hyperglycemia has been well documented, there is little available data regarding longer-term prognosis. The presence of diabetes has not only influenced disease severity but has also impacted its transmission dynamics. In this study, we followed a historical cohort of patients without previous history of diabetes who presented with moderate to severe COVID-19 and were found to have hyperglycemia (random blood glucose > 140 mg/dL) at the time of admission. We evaluated the need for antidiabetic therapy in these patients at the end of 6 months and the risk factors associated with persistent hyperglycemia determined by monthly values of self-monitored blood glucose. Of the seventy participants who were followed telephonically, 54 (77%) continued to receive antidiabetic therapy or have persistent hyperglycemia (> 140 mg/dL) at the end of 6 months. Persistent hyperglycemia at the end of follow-up, was found to be associated with a higher blood glucose at presentation.

Frailty and chronic kidney disease: associations and implications / Fragilidade e doença renal crônica: associações e implicações

ABSTRACT Introduction: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). Methods: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. Results: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. Conclusion: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

RESUMO Introdução: Fragilidade e sua associação com DRC foram estabelecidas anteriormente. O presente estudo aprofundou esta associação, estudando distribuição da fragilidade entre grupos definidos por diferentes estágios da doença. Também identificou déficits de saúde associados e explorou sua associação com taxa de filtração glomerular estimada (TFGe) e relação albumina/creatinina urinária (RAC). Métodos: Realizou-se uma pesquisa transversal em 90 pacientes com DRC Estágios 1-4 não dependentes de diálise, recrutados em três grupos estratificados de 30 participantes cada, conforme estágio da doença. Avaliou-se fragilidade usando os critérios de fragilidade de Fried e registraram-se os déficits de saúde associados usando uma lista pré-determinada. A depressão foi verificada utilizando a escala de depressão de 4 pontos. Resultados: 21,1% dos participantes eram frágeis e 43,3% eram pré-frágeis. A proporção de fragilidade nos grupos de DRC A (Estágios 1 e 2), B (Estágio 3a), e C (Estágios 3b e 4) foi de 10%, 13,3%, 40% respectivamente. A associação de déficits de saúde, incluindo comorbidades, parâmetros físicos, estado mental, atividades diárias etc. com RAC, TFGe e estágios da DRC não foi estatisticamente significativa. Cerca de um em cada dois participantes frágeis estava depressivo comparados com 14% entre não frágeis. Conclusão: A distribuição enviesada de 21% dos indivíduos frágeis identificados em nosso estudo indica associação entre fragilidade e doença renal progressiva. Indivíduos frágeis apresentaram menor TFGe, maior RAC, eram mais propensos a depressão, tinham maior índice de déficits de saúde e desempenho inferior no Índice de Atividades da Vida Diária de Barthel e WHOQOL. A identificação precoce da depressão melhoraria o atendimento desses pacientes.

PINK1 and oxidative stress in lean and obese patients with type 2 diabetes mellitus.

AIM: To compare mRNA [messenger RNA] expression of PINK1 in whole blood and the levels of biomarkers of Oxidative Stress (mitochondrial DNA [mtDNA] content & Total Antioxidant status [TAS]) in newly diagnosed lean and obese patients with T2DM. METHODS: Newly diagnosed patients of T2DM were enrolled in this study. The patients were divided into two groups of 30 patients each, lean (BMI < 18.5 kg/m2) and obese (BMI > 25 kg/m2). mRNA expression of PINK1 & mtDNA content was measured by real time PCR. Serum TAS was measured using a commercially available kit. RESULTS: There was a 1.78-fold decrease in mRNA expression of PINK1 in obese group compared to the lean group. Mean mtDNA content was 300.82 ± 169.66 in the obese group and 332.78 ± 147.07 in the lean group (p = 0.06). Mean levels of TAS was 5.39 ± 2.28 µM Trolox Equivalents in the obese group and 3.85 ± 3.33 µM Trolox Equivalents in the lean group (p = 0.001). CONCLUSION: The T2DM patient with obesity had greater OS than the lean patients. Thus, there is a compensatory increase in antioxidants in obese patients with T2DM. Our findings also suggest that decreased levels of PINK1 in obese group are unable to protect the mitochondria against OS leading to decreased mtDNA content. Does it also result in beta cell dysfunction or contribute to insulin resistance in obese patients with T2DM needs to be explored.

Frailty and chronic kidney disease: associations and implications.

INTRODUCTION: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). METHODS: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. RESULTS: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. CONCLUSION: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Differential Expression of Suppressor of Cytokine Signaling and Interferon Gamma in Lean and Obese Patients with Type 2 Diabetes Mellitus.

Background: The model of obesity-induced insulin resistance has long been used to explain the development of type 2 diabetes mellitus (T2DM) in obese individuals (body mass index (BMI) > 25 kg/m2), but this model failed to explain the development of the disease in lean individuals (BMI < 18.5 kg/m2). Defects in the insulin signaling pathway have been postulated to play a role in these patients, particularly in suppressors of cytokine signaling (SOCS) proteins, which are involved in the downregulation of insulin transduction. The expression of SOCS is also known to be induced by cytokines such as interferon gamma (IFN-γ). It is still not clear whether these pathways operate differently in lean versus obese patients with T2DM. Therefore, this pilot study was designed to study the expression of SOCS1, SOCS3, and IFN-γ in lean and obese patients with T2DM. Objectives: The levels of IFN-γ in serum and the messenger RNA (mRNA) expression of SOCS (SOCS1 and SOCS3) and IFN-γ genes in whole blood in lean and obese patients with T2DM. Methods: Sixty newly diagnosed T2DM patients (not on any pharmacotherapy) were enrolled and divided into 2 groups of lean (BMI < 18.5 kg/m2) and obese (BMI > 25 kg/m2) patients (n = 30 per group). Serum IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA), and mRNA expression of IFN-γ, SOCS1, and SOCS3 was measured by real-time polymerase chain reaction (PCR) using the ∆∆ Ct method. Results: Serum IFN-γ levels were 10.83 ± 5.81 pg/mL in the lean group and 9.35 ± 5.14 pg/mL in the obese group (P = 0.02). Fasting serum insulin levels were 16.07 ± 8.39 µIU/mL in the lean group and 27.11 ± 4 .91 µIU/mL in the obese group (P = 0.001). There was a 3.16-fold increase in mRNA expression of IFN-γ and a 1.3-fold increase in mRNA expression of SOCS1 in the lean group compared to the obese group. mRNA expression of SOCS3 was similar in both groups. Conclusions: The level of IFN-γ increased at both transcriptional and translational levels, and mRNA expression of SOCS1 was higher in the lean group than in the obese group. The SOCS protein is a known negative regulator in insulin signaling pathways. Thus, our findings and available scientific literature suggest that IFN-γ might impair the insulin signaling pathway to a greater extent in lean patients than in obese patients via induction of SOCS1. This signaling pathway could be a major contributing factor to hyperglycemia in lean patients with T2DM compared with obese counterparts. This suggests that different therapeutic approaches to these groups might be of greater benefit in the treatment of T2DM.

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders.

OBJECTIVE: We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST). METHOD: Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45 mg/day or ST 25-200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL. RESULT: We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs. CONCLUSION: Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

Correlation between telomere length and efficacy of oral and long-acting injectable antipsychotics on severity and cognitive impairment of schizophrenia.

OBJECTIVE: To study the correlation between telomere length (TL) and long-acting injectable (LAI) and oral atypical antipsychotic (OAA) efficacy on schizophrenia (SCZ) severity and cognitive impairment. METHODS: Sixty Schizophrenia patients of 18-50 years and of either sex were included in a 12-week study. Thirty patients were recruited in each group, LAI and OAA. Positive and Negative Syndrome Scale (PANSS) and National Institute of Mental Health and Neuro-Sciences (NIMHANS) neuropsychological battery tests were evaluated at baseline and 12 weeks. TL was estimated at baseline. RESULTS: Both groups showed a significant improvement in PANSS and NIMHANS battery test scores after treatment (p < 0.001) within the group, though not between the groups. Mean TL at baseline was 407.58 ± 143.93 and 443.40 ± 178.46 in LAI and OAA groups respectively. A significant negative correlation (r = -0.28, p = 0.03) of TL was seen with the mean change in negative PANSS score after treatment. CONCLUSIONS: LAI antipsychotics are similar to OAA in decreasing the disorder severity and improving the cognitive impairment in schizophrenia. Also, patients who have shorter TL show greater improvement in the negative PANSS score. Hence, TL holds the potential of predicting antipsychotic drug response in schizophrenia patients.KEY POINTSLong-acting injectable antipsychotic was comparable to oral atypical antipsychotics in bringing out improvement in disorder severity, cognitive functions over 12 weeks.Shorter telomere length has been found to be associated with a greater response in negative symptoms of schizophrenia.

Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy.

BACKGROUND: Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1ß) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups. METHODS: Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1ß levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups. RESULTS: The serum CCL2 level decreased significantly (p < .001) from 327.95 ±â€¯59.07 pg/ml to 207.02 ±â€¯41.50 pg/ml in the valproate group and from 420.65 ±â€¯83.72 pg/ml to 250.06 ±â€¯46.05 pg/ml in the add-on levetiracetam group. Serum IL-1ß level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups. CONCLUSIONS: The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1ß levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated.

Role of Cervical Phosphorylated Insulin-Like Growth Factor-Binding Protein 1 (phIGFBP1) for Prediction of Successful Induction Among Primigravida with Prolonged Pregnancy.

PURPOSE OF THE STUDY: To estimate and to compare the levels of cervical phIGFBP-1 among primigravida with prolonged pregnancy, with and without successful induction of labor (IOL). METHODS: A diagnostic study (cross-sectional study design) was conducted in our institution from November 2016 to April 2018 on 84 primigravida at ≥ 41 weeks with uncomplicated singleton pregnancy. The results were analyzed using SPSS software and receiver operating characteristics curves to determine the best cutoff using Youden Index. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive (+ LR) and negative likelihood ratio (- LR) were calculated. P value < 0.05 was considered significant. Logistic regression analysis was used to determine the predictive ability of the three markers for successful IOL. RESULTS: The cutoff level of phIGFBP-1, Bishop score (BS) and transvaginal cervical length (TVL) were 7.8 µg/l, 3 and 3.5 cm, respectively. The sensitivity, specificity, PPV, NPV, + LR and - LR of phIGFBP-1 (> 7.8 µg/l) were 0.87, 0.87, 0.89, 0.85, 6.76 and 0.15, respectively. Using logistic regression analysis, phIGFBP-1 was found to be the best predictor of successful IOL (OR 44.200; 95% CI 12.378-157.831, p < 0.001). CONCLUSION: phIGFBP-1 is a strong independent predictor successful IOL as compared to TVL and BS in primigravida with prolonged pregnancy.

Comparison of Sequential Organ Failure Assessment (SOFA) and Sepsis in Obstetrics Score (SOS) in Women with Pregnancy-Associated Sepsis with Respect to Critical Care Admission and Mortality: A Prospective Observational Study.

OBJECTIVE: We aimed to determine performance of sequential organ failure assessment (SOFA) and Sepsis in Obstetrics Score (SOS), in women with pregnancy-associated sepsis (PAS) with respect to critical care admission and mortality. METHODS: Obstetric patients with PAS fulfilling any 2 of the quick SOFA (qSOFA) criteria were enrolled as cases. The various parameters of SOFA and SOS were recorded at admission and compared for outcomes. RESULTS: Critical care was required in 32 (50.7%) patients and associated mortality was high (31.7%). For our study population, a threshold of SOFA ≥ 6 had the best combination of sensitivity (84.4%) and specificity (61.3%) for critical care admission. For SOS, a cut-off value of ≥ 6 gave best sensitivity (64%) and specificity (40%) for the same. CONCLUSIONS: SOFA was far more predictive of patient's critical condition as well as mortality compared to SOS. SOFA was superior to SOS in determining critical care admission and mortality for PAS.

Chromium Exposure in Late Gestation Period Caused Increased Levels of Cr in Brain Tissue: Association with Alteration of Activity and Gene Expression of Antioxidant Enzymes of F1 and F2 Generation Mice.

Chromium is a micronutrient which has found frequent use as supplements during pregnancy and could have a role in altering the antioxidant status in the brain. The present study was undertaken to estimate chromium levels in the brain, antioxidant enzyme activity with their gene expression, and learning and memory parameters on F1 and F2 generation mice when the F0 was exposed to chromium. The chromium levels in the brain were estimated using atomic absorption spectrophotometer. The enzyme activity of glutathione-s-transferase (GST) and catalase (CAT) was estimated and their gene expression was evaluated using RT-PCR. The spatial memory was tested using Morris water maze. The learning and recall memory was tested using the step down latency paradigm. The chromium levels were significantly raised in animals treated with Cr per se in F1 generation and quercetin cotreatment reduced the Cr levels in brain significantly. The enzyme activity of GST was significantly less in Cr-treated animals of both generations and this effect was significantly reversed on cotreatment with quercetin. The gene expression of GST matched the enzyme activity. However, catalase activity did not show significant decrease with Cr but cotreatment with quercetin resulted in significant decrease compared with control and this effect was not matched by its gene expression. We observed no significant change in learning and memory parameters in both generations following Cr exposure. Thus, this study demonstrates that chromium exposure in gestation causes changes in enzyme activity especially GST and this change was matched by change in gene expression in GST but not CAT. There was no effect on memory at the given dose.

Serial Serum Lactic Acid in Pregnancy-Associated Sepsis for Maternal Outcome.

OBJECTIVE: To correlate serial monitoring of lactic acid in pregnancy-associated sepsis (PAS) subjects with maternal prognosis. METHODS: All pregnant, post-abortal (2 weeks) and postpartum women with suspected sepsis fulfilling any 2 of the Quick Sequential Organ Failure Assessment criteria were considered as cases. Lactic acid was measured at 0, 24 and 48 h of admission, and lactate clearance was calculated. RESULTS: The mean value of lactic acid was significantly higher in the Intensive Care Unit (ICU) group than the Non-ICU group at 0, 24, and 48 h with values being (6.00 ± 2.46 mmol/l vs 3.25 ± 1.92 mmol/l), (4.44 ± 2.24 mmol/l vs 2.91 ± 1.77 mmol/l) and (5.65 ± 2.91 mmol/l vs 2.99 ± 1.93 mmol/l), respectively. Lactic acid in the survivor group was significantly lower as compared to the mortality group (3.79 ± 0.32 mmol/l vs 7.3 ± 0.56 mmol/l). A cut-off of 3.8 mmol/l with area under the curve of 0.814 has a sensitivity of 84% and specificity of 68% for predicting ICU admission. The mean lactate clearance was 46% in cases who survived and 22.5% in cases who had mortality. When lactate clearance was 60%, no mortality was seen, whereas when there was 100% rise in lactic acid, they all had mortality. CONCLUSION: The mean lactic acid at 0, 24 and 48 hours was significantly higher in the ICU group as compared to the Non-ICU group. Serum lactic acid at zero hours of the presentation was significantly higher in ICU cases. Lactate clearance (fall) helps to prognosticate as fall of ≥ 60% lactic acid level is associated with 100% survival, whereas a rise of 100% in serum lactic acid is associated with 100% mortality.

Exposure to Nitrogen Dioxide (NO2) from Vehicular Emission Could Increase the COVID-19 Pandemic Fatality in India: A Perspective.

The corona virus-2019 (COVID-19) is ravaging the whole world. Scientists have been trying to acquire more knowledge on different aspects of COVID-19. This study attempts to determine the effects of COVID-19, on a large population, which has already been persistently exposed to various atmospheric pollutants in different parts of India. Atmospheric pollutants and COVID-19 data, obtained from online resources, were used in this study. This study has shown strong positive correlation between the concentration of atmospheric nitrogen dioxide (NO2) and both the absolute number of COVID-19 deaths (r = 0.79, p < 0.05) and case fatality rate (r = 0.74, p < 0.05) in India. Statistical analysis of the amount of annual fossil fuels consumption in transportation, and the annual average concentration of the atmospheric PM2.5, PM10, NO2, in the different states of India, suggest that one of the main sources of atmospheric NO2 is from fossil fuels combustion in transportation. It is suggested that homeless, poverty-stricken Indians, hawkers, roadside vendors, and many others who are regularly exposed to vehicular exhaust, may be at a higher risk in the COVID-19 pandemic.

Evaluation of Placental VEGFA mRNA Expression in Preeclampsia: A Case Control Study.

OBJECTIVE: The aim of our case-control study was to determine expression of VEGFA mRNA in placentae of preeclamsia (PE) versus uncomplicated pregnancy to further clarify its differential expression in pregnancy hypertensive disorders. STUDY DESIGN: The PE group was subdivided into severe and non-severe; those with or without HELLP syndrome and placental VEGFA characteristics were compared for these cohorts. Additionally, the neonatal and maternal outcomes were recorded. The quantification of placental VEGFA was done using quantitative real-time PCR and results were expressed as fold change. RESULTS: Out of 42 PE cases, 23 (55%) were non-severe and 19 cases (45%) were severe PE. Out of 19 severe PE patients, 8 (42%) were HELLP syndrome (complete HELLP) and remaining 11 (58%) were non-HELLP severe PE. Compared to controls, the true fold change in PE, HELLP, non-HELLP, severe PE, non-severe PE was - 2.186, - 13.333, - 6.698, - 8.950 and 1.466, respectively. CONCLUSIONS: Our results showed a lowered VEGFA expression in PE placentae compared to uncomplicated controls. The finding of initial increase of VEGFA in non-severe PE and subsequent marked lowering in HELLP strengthens the existing hypothesis of decompensated VEGF being a major role player in PE.

Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice: improvement with quercetin.

The increased exposure to cadmium (Cd) through environmental pollutants, food and cigarette smoke is a concern worldwide. The association of Cd with impaired learning disabilities led us to hypothesise that cadmium levels in brain tissue could be dose-dependently related to the extent of memory impairment and oxidative stress. In this study, we proposed to study whether cadmium exposure to dams could alter the brain Cd levels, memory parameters, antioxidant enzymes in brain and their gene expression in the F1-F2 generation mice and whether quercetin could modulate this effect. Animals were administered Cd alone and in combination with quercetin for 7 days during their gestation period. Their newborn pups (F1 and F2 mice) were reared until adulthood and were tested for memory using Morris water maze and step-down latency test. The brain tissue of F1 mice was collected. Cd levels were estimated using the atomic absorption spectrophotometer. G-S-transferase (GST) and catalase (CAT) activity were measured and fold increase in their respective gene expression was observed using the RT-PCR method. Cd levels were significantly increased in the brain tissue of animals exposed to Cd but cotreatment with quercetin showed decreased levels in both generations. Memory impairment was observed in animals of F1 generation exposed to Cd and cotreatment with quercetin (100 mg/kg) reversed this effect. Cd exposure significantly enhanced both activity and expression of GST and CAT in the brain tissue of F1 generation mice and quercetin attenuated this effect. In F2 generation, results were variable. GST activity and expression increased with Cd and decreased with quercetin cotreatment. However, CAT activity showed no significant change despite a decrease in gene expression. Quercetin cotreatment enhanced activity as well gene expression in F2 generation. Our study insinuates that Cd levels could act as a predictor of memory impairment and altered enzyme activity and gene expression in brain tissue. Quercetin helped to reduce Cd levels in brain tissue of F1 and F2 generation and modulated the antioxidant system of the cell by affecting expression of antioxidant enzymes at the transcription level.

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin.

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100 mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100 mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25 mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

Role of Survivin and p53 Expression in Response of Primary Culture of Ovarian Cancer Cells to Treatment With Chemotherapeutic Agents.

BACKGROUND: Ovarian cancer is associated with a high relapse rate and is the fifth leading cause of cancer deaths in women. The genetic profile of a tumor is responsible for deciding response to chemotherapeutic agents. In this study, we investigate the relation between survivin and p53 expression and response to chemotherapeutic agents of primary cultures of ovarian cancer cells established from ascitic fluid. MATERIALS AND METHOD: Ascitic fluid and Dulbecco's modified Eagle medium was mixed in equal proportion in culture flasks and incubated to establish primary culture. The cells were treated with different combinations of carboplatin and paclitaxel with and without survivin small interfering RNA transfection. Cell survival was estimated by MTT assay. Survivin and p53 expression was quantified by real-time polymerase chain reaction. RESULTS: Out of 19 ascitic fluid samples, 13 primary cultures of ovarian cancer cells were established. The half maximal inhibitory concentration doses of carboplatin (≥70 µg/mL) and paclitaxel (≥18 µg/mL) were high for 10/13 and 5/13 patients, respectively. Survivin messenger RNA expression was significantly downregulated on treatment with carboplatin (100 µg/mL), paclitaxel (12.5 µg/mL), and a combination of carboplatin (50 µg/mL) and paclitaxel (6.25 µg/mL). Only paclitaxel-treated ovarian cancer cells showed decrease in expression of p53. Survivin small interfering RNA increased sensitivity of the primary cultures to chemotherapeutic agents. CONCLUSIONS: The present study highlights the fact that establishing primary cultures from ascitic fluid may help to develop personalized treatment regime for individual patients based on their molecular profile. Our study also shows that supplementing taxols drugs with survivin inhibitors may prove to be beneficial in the treatment of ovarian cancer patients.

Establishment of Primary Cell Culture From Ascitic Fluid and Solid Tumor Obtained From Epithelial Ovarian Carcinoma Patients.

OBJECTIVE: Ovarian cancer is the seventh leading cause of cancer death worldwide. This is mainly due to late diagnosis and high rate of relapse and resistance following chemotherapy. In the present study, we describe simple and cost-effective method to establish primary culture from ascitic fluid and solid tumor obtained from epithelial ovarian carcinoma patient, which may provide a better tool for in vitro testing of drug sensitivity and designing individualized treatment protocol. METHODS: Complete Dulbecco modified Eagle medium (DMEM) was prepared by supplementing DMEM with 10% fetal bovine serum and antibiotics (ciprofloxacin and amphotericin B). Establishment of primary culture of ovarian cancer cells from ascites fluid and solid tumor was done by using complete DMEM media. RESULTS: Primary cultures of ovarian cancer cells were established from ascitic fluid and solid tumor tissue. Of the 7 ascitic fluid samples, we were able to establish 5 primary cultures of ovarian cancer cells. All the 7 samples were diagnosed as serous papillary adenocarcinoma. Some fibroblasts were also attached to culture flask on day 4; they were removed by exposing them to trypsin for a brief period. On day 7, grape-like clusters were visualized under inverted microscope. The cells became confluent on the 10th and 11th day and showed cobblestone appearance, which is a hallmark of ovarian cancer cells. Senescent irregularly shaped cells that have ceased dividing were seen after 8 to 10 passages. CONCLUSION: This study highlights the fact that establishing primary cultures from ascitic fluid or solid tumor tissue may help us to understand the molecular profile of the cancer cells, which allow us to select the best chemotherapeutic agent for ovarian cancer patients and thus take a step toward patient-tailored therapy so that patients are not exposed to drugs to which they are not likely to respond.

Prediction of preeclampsia in primigravida in late first trimester using serum placental growth factor alone and by combination model.

We investigated a placental growth factor alone and combined clinical (mean arterial pressure, MAP), biophysical (uterine artery pulsability index, PI) and biochemical (placental growth factor, PLGF) model for predicting preeclampsia in late first trimester. The inclusion criteria was primigravida (<40 years) attending their first hospital visit with singleton pregnancy at 11-14 weeks of gestation. Of the enrolled and followed 291 subjects, 35 (12%) later developed PE (5.8%)/GH (6.2%). An equal number of randomised women with normotensive non-proteinuric course were considered as reference group. For preeclampsia, PLGF alone had detection rate of 40% and 51% with 5% and 10% FPR, respectively. On addition of MAP, the AUC improved to 0.937 for PE. Further, addition of mean PI slightly improved AUC to 0.965. This signifies that a model with all three markers had better prediction of preeclampsia rather than PLGF alone. Impact statement In view of high morbidity and mortality due to hypertensive disorders in pregnancy, there has been extensive research for developing markers to detect/screen the condition in early pregnancy. Several such markers have been tested in their individual capacities and in combination during early pregnancy. Most of these studies have originated from high income countries and focussed mainly on the second trimester of pregnancy. We investigated a placental growth factor alone and combined clinical (mean arterial pressure, MAP), biophysical (uterine artery pulsability index, PI) and biochemical (placental growth factor, PLGF) model for predicting preeclampsia in the first trimester in primigravida (<40 years). A nested case control model was used for our study. For preeclampsia, PLGF alone had detection rate of 40% and 51% with 5% and 10% FPR, respectively. On addition of MAP, the AUC improved to 0.937 for PE. Further, addition of mean PI slightly improved AUC to 0.965. The present study has been done in an Indian subcontinent setting (where maternal mortality related to preeclampsia are even higher) where very limited studies are available for the role of either PLGF or in combinations for prediction of preeclampsia. Our research pointed shows better predictability for PE when a combination of markers is used especially in low-risk nulligravida. These are easy, cheap and non-invasive measurements that can be taken in all women at their first routine antenatal visit.