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 β-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, P=0.001), p’p’-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, P=0.003), and o’p’-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. Linear positive correlations were observed between period of gestation (POG) and 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.

Can Metabolic Factors be Used Prognostically for Short-Term Mortality in HIV-Infected Patients?

Background: Metabolic abnormalities are common throughout the course of human immunodeficiency virus (HIV) infection and may occur either due to HIV infection or as a result of side effects of antiretroviral therapy. It has been established that dyslipidemia and dysglycemia associated with HIV disease reduce the long-term survival of the patients; but their role for predicting prognosis of short-term mortality in HIV patients is unknown. Aim: To study dyslipidemia and dysglycemia as a prognostic indicator for short-term mortality (3 months) in HIV patients. Subjects and Methods: An observational; prospective study was conducted at a tertiary care center over a period of 6 months. Consecutive HIV-positive patients hospitalized (both; HIV status known prior to hospitalization and the diagnosis made for the first time at admission) in medical wards from March to May 2010 were studied. All patients had their random blood sugars; fasting blood sugars (if possible); fasting lipid profile; and cluster of differentiation 4 (CD4) counts tested at the time of enrollment. The patients were followed for a period of 3 months; at the end of which they were categorized as survivors and non-survivors; and the demographic; clinical; and investigational parameters were compared between the above groups. Data was analyzed by applying Mann-Whitney U test; two sample t-test; Fisher-Exact test; and stepwise logistic regression analysis of significance; using the computer-based program; Stata; version 11.1. Results: A total of 82 patients were enrolled for the study of which 64 (78.05) were males and 18 (21.95) were females; with a mean (SD) age of 34.00 (7.0) years. The mean CD4 count was 206.23 (129.5) cells/mm 3 . The overall mortality within 3 months was 20.7 (17/82). Mycobacterium tuberculosis as opportunistic infection was found in 42 patients; out of which 13 expired (P

Can Metabolic Factors be Used Prognostically for Short-term Mortality in HIV-infected Patients?

Metabolic abnormalities are common throughout the course of human immunodeficiency virus (HIV) infection and may occur either due to HIV infection or as a result of side effects of antiretroviral therapy. It has been established that dyslipidemia and dysglycemia associated with HIV disease reduce the long-term survival of the patients; but their role for predicting prognosis of short-term mortality in HIV patients is unknown. Aim: To study dyslipidemia and dysglycemia as a prognostic indicator for short-term mortality (3 months) in HIV patients. Subjects and Methods: An observational; prospective study was conducted at a tertiary care center over a period of 6 months. Consecutive HIV-positive patients hospitalized (both; HIV status known prior to hospitalization and the diagnosis made for the first time at admission) in medical wards from March to May 2010 were studied. All patients had their random blood sugars; fasting blood sugars (if possible); fasting lipid profile; and cluster of differentiation 4 (CD4) counts tested at the time of enrollment. The patients were followed for a period of 3 months; at the end of which they were categorized as survivors and non-survivors; and the demographic; clinical; and investigational parameters were compared between the above groups. Data was analyzed by applying Mann-Whitney U test; two sample t-test; Fisher-Exact test; and stepwise logistic regression analysis of significance; using the computer-based program; Stata; version 11.1. Results: A total of 82 patients were enrolled for the study of which 64 (78.05) were males and 18 (21.95) were females; with a mean (SD) age of 34.00 (7.0) years. The mean CD4 count was 206.23 (129.5) cells/mm 3 . The overall mortality within 3 months was 20.7(17/82). Mycobacterium tuberculosis as opportunistic infection was found in 42 patients; out of which 13 expired (P

Profile of CD4 Counts and Symptoms in HIV Positive Patients on and not on Antiretroviral Therapy.

This communication pertains to a study on analysis of the profile of CD4 counts and symptoms in HIV infected adult subjects on and not on antiretroviral therapy. Clinical symptoms in HIV infected patients attending a tertiary care hospital in north India were recorded by direct questioning. Differences in distribution of categorical variables were analyzed using chi-square test. A p-value <0.05 was considered statistically significant. 317 enrolled HIV positive patients, 271/317 (85.5%) patients were symptomatic. The common symptoms were weakness (65.6%), bodyache and joint pain (63.4%), lethargy and fatigue (62.5%), prolonged fever (53.3%), weight loss (47.6%), cough (44.5%), loss of appetite (44.2%) and chronic diarrhoea (40.1%). Most symptoms were found significantly less frequently in patients on antiretroviral therapy (ART). High CD4+ T-cell counts were negatively associated with symptoms. The overall proportion of symptomatic patients was significantly higher than the number with an etiologically documented opportunistic infections (32.5%). Pulmonary tuberculosis (30.9%) was the most frequently documented opportunistic infection. Antiretroviral therapy appears to be beneficial in reducing symptoms in HIV positive patients. Affordable high quality laboratory diagnostic facilities for the diagnosis of opportunistic infections under the public health program will help to obtain an accurate picture of the range of opportunistic infections in HIV patients in India.

Molecular identification of methanogenic archaea from Surti buffaloes (bubalus bubalis), reveals more hydrogenotrophic methanogens phylotypes

Methane emissions from ruminant livestock are considered to be one of the more potent forms of greenhouses gases contributing to global warming. Many strategies to reduce emissions are targeting the methanogens that inhabit the rumen, but such an approach can only be successful if it targets all the major groups of ruminant methanogens. Therefore, a thorough knowledge of the diversity of these microbes in breeds of buffaloes, as well as in response to geographical location and different diets, is required. Therefore, molecular diversity of rumen methanogens in Surti buffaloes was investigated using 16S rRNA gene libraries prepared from pooled rumen contents from three Surti buffaloes. A total of 171 clones were identified revealing 23 different sequences (phylotypes). Of these 23 sequences, twelve sequences (12 OTUs, 83 clones) and 10 sequences (10 OTUs, 83 clones) were similar to methanogens belonging to the orders Methanomicrobiales and Methanobacteriales, and the remaining 1 phylotype (5 clones) were similar to Methanosarcina barkeri. These unique sequences clustered within a distinct and strongly supported phylogenetic group. Further studies and effective strategies can be made to inhibit the growth of Methanomicrobiales and Methanobacteriales phylotypes to reduce the methane emission from rumen and thus help in preventing global warming.

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

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

Study of bio-physico-chemical parameters of Mothronwala swamp, Dehradun (Uttarakhand).

Aquatic biodiversity is one of the most essential characteristics of the aquatic ecosystem formaintaining its stability and a means of coping with any environmental change. The entire stretch of the Mothronwala swamp has rich riparian vegetation for providing conducive environment for the growth of aquatic organisms. The present work has been undertaken to study the bio-physico-chemical characteristics of the swamp. The data on physico-chemical environmental variables (temperature, total dissolved solutes, size and composition of substratum, pH, dissolved oxygen, alkalinity chlorides, and hardness) have been given under the present contribution. A total of 16 genera of aquatic insects belonging to orders Trichoptera, Coleoptera, Hemiptera, Ephemeroptera, Odonata and Phylum Mollusca represented the macroinvertebrates of Mothronwala swamp. The fresh water swamp of Mothronwala is under threat due to human interference and other anthropogenic activities. Some of the natural and anthropogenic environmental problems of the Mothronwala swamp have been identified and the ameliorative measures for the protection of aquatic environment and the conservation measures for the swamp have been suggested. The qualitative study revealed the present status of the aquatic biodiversity of the swamp and also about the physico-chemical parameters, which would be very helpful for policy makers to take precautionary measures to save the swamp.

Tuberculosis presenting as osteolytic soft tissue swellings of skull in HIV positive patient: a case report.

We present a clinical case report of a 40-year old HIV positive male patient presenting with fever, cough with expectoration and osteolytic, cystic, multiple soft tissue swellings of skull (aspirate showing AFB). The various clinical possibilities are discussed along with interpretation of subsequent investigations.

Advanced glycosylated end products-mediated activation of polymorphonuclear neutrophils in diabetes mellitus and associated oxidative stress.

Two important consequences of hyperglycemia in diabetes are development of oxidative stress and formation of advanced glycation end products (AGE) which are known to be associated with diabetic complications. Relationship between AGE formation and development of oxidative stress (OS) is yet to be established. In the present study, the involvement of AGE in PMN-mediated ROS generation and the associated OS were investigated in type 2 diabetic mellitus (DM) patients. We assessed OS parameters (serum MDA, FRAP and GSH), PMN oxidative functions (respiratory burst and superoxide production) and total serum AGE in 90 subjects divided equally in three groups--control group, Group I consisting of type 2 diabetic patients without microvascular complications and Group II consisting of type 2 diabetic patients with microvascular complications. PMNs isolated from both groups (I and II) exhibited higher level of respiratory burst (RB) and produced increased amount of superoxide anion as compared to the controls. The increase was more pronounced in diabetes with complications, as compared to those without. Serum malondialdehyde (MDA) level was elevated, whereas glutathione (GSH) and ferric reducing ability of plasma (FRAP) levels were significantly reduced in diabetes as compared to the controls, suggesting the presence of oxidative stress in DM. A positive correlation between PMN oxidative function and OS parameters suggested the involvement of PMN in the development of OS in DM. Serum AGE level was also elevated in diabetic groups as compared to the controls. Further, the positive correlation between serum AGE level and PMN oxidative function suggested the involvement of AGE in increased RB and generation of reactive oxygen species (ROS) by resting diabetic PMN. The results of the study indicate that AGE-PMN interaction possibly upregulates NADPH oxidase, leading to enhanced ROS generation and thus contributes to the pathogenesis in diabetes.

Low prevalence of hepatitis B virus and hepatitis C virus co-infection in patients with human immunodeficiency virus in Northern India.

AIM: To study the prevalence of HBV and HCV co-infection in patients with HIV attending a referral hospital in Northern India. METHODS AND MATERIAL: The study cohort included six hundred and twenty consecutive HIV infected patients who were studied for co-infection with HBV/HCV or both. It included four hundred and seventy two male and one hundred and forty eight female patients between the age group 25-50 years. HBV and HCV infection was diagnosed by ELISA. Other routine investigations were also done. RESULTS: Out of a total of 620 consecutive HIV infected patients studied, HBV co-infection was detected in 14/ 620 (2.25%) patients and HCV co-infection in 10/620 (1.61%) patients and dual co-infection (HBV/HCV) in 1/620(0.16%). The mode of transmission of HBV was sexual contact in all (100%), while for HCV it was sexual contact in 5 patients (50%), blood transfusion in 4 patients (40%) and intravenous drug use (IDU) in 1 patient (10%). CONCLUSION: The prevalence of co-infection with HBV/HCV is much lower in our study population as compared to that reported in Western literature.

Biochemical parameters of plants as indicators of air pollution.

In the present study species like Mangifera indica, Linn., Cassia fistula, Linn., and Eucalyptus hybrid were exposed to different air pollution load for short duration (active biomonitoring). Variation in biochemical parameters like chlorophyll, protein, soluble sugar free amino acid, ascorbic acid, nitrate reductase, superoxide dismutase and peroxidase in the leaves were found to be pollution load dependent. These variations can be used as indicators of air pollution for early diagnosis of stress or as a marker for physiological damage to trees prior to the onset of visible injury symptoms. Just by analyzing these biochemical indicators air quality can also be assessed.

Protective effect of melatonin against propoxur-induced oxidative stress and suppression of humoral immune response in rats.

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

Immunotoxicity of phosphamidon following subchronic exposure in albino rats.

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

Bone marrow abnormalities in HIV disease.

Bone marrow abnormalities are frequently observed in HIV infected individuals at all stages of the disease. The most common abnormal finding is dysplasia affecting one or more cell lines. Erythroid dysplasia is the most common type of dysplasia and is recognized in over 50% of HIV infected patients, abnormal granulocytic and megakaryocytic development is encountered in one-third of patients. Plasma cells are strikingly increased in bone marrow of HIV infected patients. It may represent a physiological response to antigenic stimulation by viruses, other infective agents or secondary to dysregulated B-cell proliferation due to HIV. Herein we present a review discussing the various bone marrow abnormalities associated with the HIV disease.

Study of bone marrow abnormalities in patients with HIV disease.

AIM: Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS and to find their association with peripheral hematological abnormalities. METHODS: Seventy four patients of HIV/AIDS were included in the study. The patients had anemia, leucopenia, thrombocytopenia or pyrexia of unknown origin (PUO) as indications for bone marrow examination. A complete blood count, relevant biochemical investigations, HIV RNA load and CD4 positive lymphocyte counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AIDS and those without AIDS according to NACO criteria. RESULTS: Majority of patients (72.9%) had AIDS. Bone marrow was normocellular in 78.95% of non-AIDS and 74.55% of AIDS, hypocellular in 5.26% of non-AIDS and 7.27% of AIDS, hypercellular in 15.79% of non-AIDS and 18.18 % of AIDS patients. Myelodysplasia was present in 21.05% of non AIDS and 36.46% of AIDS and the most common series affected was granulocytic (15.79% of total in non-AIDS and 30.9% in AIDS). Dysplasia was statistically significantly associated with lower CD4 count (p = 0.031) and anemia (p = 0.013). Myelodysplasia was apparent even before patients developed anemia (16.67%). Increased plasma cells in bone marrow were observed in 57.89% of non-AIDS and 65.45% of AIDS, whereas decreased lymphoid cells were seen in 36.84% of non AIDS and 60.00% of AIDS patients. CONCLUSIONS: Myelodysplasia is found in 32.43% of cases of HIV/AIDS and is more common in AIDS than in non AIDS patients. Granulocytic series is most commonly associated with evidence of dysplasia. Myelodysplasia is more common in patients with CD4 count < 200/microl and in patients with anemia. 54.05% of patients had decreased lymphoid cells in bone marrow and it was more commonly seen in AIDS than in non AIDS.

HIV disease presenting as parotid lymphoepithelial cysts: a presumptive diagnosis of diffuse infiltrative lymphocytic syndrome (DILS).

Diffuse infiltrative lymphocytic syndrome (DILS), is a rare manifestation of human immunodeficiency virus (HIV) disease which is characterized by a diffuse visceral CD8 lymphocytic infiltration, a persistent CD8 lymphocytosis, bilateral parotid swelling and cervical lymphadenopathy. We describe a case of a HIV positive female, who had bilateral parotid swelling and CD8 lymphocytosis, to illustrate this rare clinical entity.

A comparative study of clinico-radiological spectrum of tuberculosis among HIV seropositive and HIV seronegative patients.

BACKGROUND: A study to determine the prevalence of human immunodeficiency virus (HIV) infection among tuberculosis patients and to compare the clinico-radiological spectrum of tuberculosis among HIV seropositive and seronegative patients was carried out in the Department of TB and Chest Diseases, CSM Medical University, Lucknow (Uttar Pradesh), India. METHODS: A total of 1105 radiologically and/or bacteriologically confirmed patients of tuberculosis were screened for HIV infection during the years 1995 to 1997 and from 2000-2001. RESULTS: Out of a total 1105 patients screened, 31(2.8%) were found to be HIV seropositive. Tuberculin positivity was less among HIV seropositive patients as compared to HIV seronegative patients (22.6% vs 76.4%; p < 0.001). There was no statistically significant difference in sputum smear positivity for acid-fast bacilli (AFB) among HIV seropositive and seronegative patients. Among HIV seropositive patients, mid and lower zone involvement, exudative lesions and mediastinal lymphadenopathy was more common as compared to the seronegative patients. CONCLUSION: HIV seropositivity rates among tuberculosis patients was 2.8 percent. The presentation of tuberculosis was more often atypical among these patients.

Reversible leg ulcer due to hydroxyurea in a case of chronic myeloid leukemia.

The cutaneous side effects of hydroxyurea are lesser known complication of long term hydroxyurea therapy in myeloproliferative disorders. We report a non-diabetic patient, who developed hydroxyurea dermopathy (leg ulcers) during long-term treatment with hydroxyurea for chronic myeloid leukemia (CML). The time course of the development of ulcers and its healing suggests that these resulted from the direct toxicity of hydroxyurea. We aim to increase clinical awareness of this problem.

Effect of ascorbic acid on stimulatory status of activated mouse peritoneal phagocytes.

Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found to be significantly stimulatory, exhibiting marked alteration at the cellular and enzyme levels. Alterations recorded were as follows--cellular yield per mouse, their protein content, lysosomal acid hydrolase levels and capability to phagocyte, all were significantly enhanced. The new stimulant was observed to produce no synergistic action on MPM when thioglycollate, BCG or endotoxin along with the same stimulated the latter. Levels of antioxidants like ascorbic acid and glutathione were found to be enhanced in elicited macrophages whereas superoxide dismutase levels varied when the three above stimulators were administered. However, the ascorbic acid elicited cells showed an increase in glutathione levels and a decrease in SOD levels but no change in total intracellular ascorbic acid levels. Further, though ascorbic acid interaction enhanced the phagocytic capability of MPM as compared to resident cells, no significant boosting of phagocytic process could be observed when each of three stimulators coupled with ascorbic acid was used for macrophage elicitation.