In vivo validation of the functional role of MicroRNA-4638-3p in breast cancer bone metastasis.

PURPOSE: Skeletal metastases are increasingly reported in metastatic triple-negative breast cancer (BC) patients. We previously reported that TGF-ß1 sustains activating transcription factor 3(ATF3) expression and is required for cell proliferation, invasion, and bone metastasis genes. Increasing studies suggest the critical regulatory function of microRNAs (miRNAs) in governing BC pathogenesis. TGF-ß1 downregulated the expression of miR-4638-3p, which targets ATF3 in human BC cells (MDA-MB-231). In the present study, we aimed to identify the functional role of miR-4638-3p in BC bone metastasis by the caudal artery injection of the MDA-MB-231 cells overexpressing mir-4638 in the mice. METHODS: MDA-MB-231 cells overexpressing miR-4638 were prepared by stable transfections. Reverse transcriptase quantitative PCR was carried out to determine the expression of endogenous miR-4638-3p and bone resorption marker genes. X-ray, micro-CT, and Hematoxylin & Eosin studies were used to determine osteolytic lesions, trabecular structure, bone mineral density, and micrometastasis of cells. RESULTS: The mice injected with MDA-MB-231 cells overexpressing miR-4638-3p decreased the expression of bone resorption marker genes, compared to MDA-MB-231 cells injection. Reduced osteolytic lesions and restored bone density by MDA-MB-231 cells overexpressing miR-4638-3p were observed. Similarly, the mice injected with MDA-MB-231 cells overexpressing miR-4638-3p showed a better microarchitecture of the trabecular network. A few abnormal cells seen in the femur of MDA-MB-231 cells-injected mice were not found in MDA-MB-231 cells overexpressing miR-4638. CONCLUSION: The identified functional role of ATF3 targeting miR-4638-3p in BC bone metastasis in vivo suggests its candidature as BC therapeutics in the future.

Bisphenol A accelerates the vascular complications in patients with Type 2 diabetes mellitus through vascular calcification-a molecular approach.

PURPOSE: Environmental pollutant Bisphenol A (BPA) strongly interacts with insulin resistance, which leads to type 2 diabetes mellitus (T2DM). Uncontrolled glucose levels in both blood and urine develops vascular complications in T2DM patients. However, glucose-controlled diabetic patients are also affected by vascular complications due to vascular calcification, and there is a lack of clinically relevant data on BPA levels available in patients with T2DM-associated vascular complications due to vascular calcification. Therefore, we measured BPA levels in T2DM-associated vascular complications and correlated systemic BPA levels with vascular calcification-related gene expression. METHODS: This study included 120 participants with T2DM and its associated vascular complications. Serum and urinary BPA were estimated using an ELISA kit, and gene expression of the study participants in peripheral blood mononuclear cells (PBMCs) was studied with quantitative real-time PCR. RESULTS: Serum and urinary BPA levels were higher in T2DM and its associated vascular complications with CVD and DN patients compared to control. Both Serum and urinary BPA had higher significance with Sirt1 (p < 0.001, p < 0.001), Runx2 (p < 0.01, p < 0.001) and IL-1beta (p < 0.001, p < 0.02) gene expression in the study groups, but, TNF-alpha significant with Serum BPA (p < 0.04), not urinary BPA (p < 0.31). CONCLUSION: BPA levels were positively correlated with lower Sirt1 and increased Runx2 in T2DM-associated vascular complications patients. Also, higher expression of IL-1beta and TNF-alpha was observed in T2DM-associated vascular complications patients. Our study is the first to associate BPA levels with vascular calcification in patients with T2DM and its associated vascular complications.

Exosomes as Theranostic Targets: Implications for the Clinical Prognosis of Aggressive Cancers.

Exosomes are extracellular vesicles produced by various cell types and extensively distributed in physiological fluids. Because of their significant role in cancer progression, they have been a focal point for the novel cancer therapy approach. Exosomes are highly efficient at transporting proteins, RNAs, and small drugs into cancer cells for therapeutic purposes. In addition to their prominent role as potential biomarkers for transporting targeted information from their progenitor cells, exosomes have also emerged as a new avenue for developing more effective clinical diagnostics and therapeutic techniques, also known as exosome theranostics. Lipids, proteins, and nucleic acids transported by exosomes were investigated as potential biomarkers for cancer diagnosis, prognosis, and future cancer treatment targets. The unique mechanism of exosomes and their therapeutic as well as diagnostic uses, also known as theranostic applications of exosomes in malignancies, are discussed in this review.

Correlation between abnormal GSK3ß, ß Amyloid, total Tau, p-Tau 181 levels and neuropsychological assessment total scores in CKD patients with cognitive dysfunction: Impact of rHuEPO therapy.

BACKGROUND: Cognitive dysfunction potentially affecting up to 60% of CKD patients. GSK-3ß plays a key role in the pathogenesis of AD and Cognitive dysfunction, contributing to Aß production and Aß-mediated neuronal death by phosphorylating tau inducing hyperphosphorylation in paired helical filaments. However, studies have shown that plasma p-Tau181 is more specific for AD and cognitive dysfunction. Anemia is a vital risk factor for cognitive dysfunction in CKD patients. EPO is usually to treat anemia in CKD and also improved in cognitive function. The aim of the study is to correlate between the impacts of rHuEPO therapy on platelet GSK3ß expression, plasma Aß, total Tau, p-Tau 181 levels and neuropsychological assessments total scores in CKD patients with Cognitive dysfunction. METHODS: The subjects, 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction patients. To correlate abnormal proteins with neuropsychological tests scoring in CKD with cognitive dysfunction subjects after the six months rHuEPO therapy. RESULTS: The p < 0.05 is considered as statistically significant. Pearson and Spearman correlation coefficient was used to determine the potential relationship between abnormal proteins with neuropsychological tests scoring in respective experimental groups. CONCLUSIONS: The use of abnormal protein levels, preferably in association with neuropsychological assessment total scores, appears to be a potential tool that can improve the CKD with cognitive dysfunction diagnosis. In post rHuEPO treatment, the altered protein abnormalities and neuropsychological assessment scores were retrieved significantly compared to pre treatment determined the clinical usefulness of rHuEpo as supplemental therapeutic agent in cognitive dysfunction in CKD.

Abnormal amyloid ß42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease.

BACKGROUND: Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid ß (Aß) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aß has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aß production. The aim of this study is to assess the antioxidant status and Aß42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction. METHODS: A total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aß42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aß level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects. RESULTS: Like AD subjects, significantly increased Aß and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects. CONCLUSION: Results suggest that elevated plasma oxidative stress and Aß were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.

Spatially directed vesicle capture in the ordered pores of breath-figure polymer films.

This work describes a new method to selectively capture liposomes and other vesicle entities in the patterned pores of breath-figure polymer films. The process involves the deposition of a hydrophobe containing biopolymer in the pores of the breath figure, and the tethering of vesicles to the biopolymer through hydrophobic interactions. The process is versatile, can be scaled up and extended to the deposition of other functional materials in the pores of breath figures.

Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia.

STUDY OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH) in subjects with postoperative dental pain along with transient insomnia induced by 5 h sleep phase advance. The present studies aimed to demonstrate the added benefit and optimal dosages of the combination product over individual ingredients alone in improving sleep and pain. METHODS: Each of the two studies was a two-centre, randomised, double-blind and double-dummy trial. In the first study, subjects were randomised into one of the following treatment arms: NS 440 mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study, subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co-primary end-points in both studies were wake time after sleep onset (WASO) and sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. RESULTS: The intent-to-treat population included 712 and 267 subjects from studies one and two, respectively. In the first study, only the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min respectively, p < 0.0001). In the second study, the NS 440 mg/DPH 25 mg combination failed to show any significant improvements vs. either component alone. CONCLUSIONS: Only the NS 440 mg/DPH 50 mg combination demonstrated improvement in both sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs. NS 440 mg. There were no serious or unexpected adverse events reported in either study. CLINICAL TRIAL REGISTRATION: NCT01280591 (study 1); NCT01495858 (study 2).

Occurrence of Perchlorate in Various Water Sources in South India.

Iodine is necessary for synthesis of thyroxine within the thyroid gland. Iodine deficiency leads to hypothyroidism and goitre. Sometimes, even when sufficient iodine is present in food and water, goitre occurs. This could be due to some other competing ions in the ingested food and water, which prevent incorporation of iodine into the thyroid gland. Perchlorate is one such ion and has thirty times more affinity to thyroid, than iodine. Perchlorate is discharged into the environment by fireworks and explosives industries. Hence, the perchlorate levels would be higher in and around such industries. This study was done to determine the perchlorate exposure to humans in their habitat. In this study, perchlorate levels in different water sources in localities with and without such industries were ascertained. The estimation was done by two methods (i) Thionine ion pair spectrophotometry and (ii) ion exchange chromatography with conductivity detection methods. In the results, perchlorate level was significantly high in different water sources of industrialized areas, when compared to non-industrial areas. These high levels could be the explanation for the high prevalence of goitre in areas with sufficient iodine availability.

Polychlorinated biphenyls induced oxidative stress mediated neurodegeneration in hippocampus and behavioral changes of adult rats: anxiolytic-like effects of quercetin.

Polychlorinated biphenyls (PCBs) are extremely toxic environmental contaminant speculated to accelerate neurochemical and behavioral damages. Developmental and behavioral development relies on the proper functioning of the endogenous neurotransmitters that remain the pivotal target of neurotoxicants. This study intent to evidence the neuroprotective efficacy of quercetin against PCBs induced hippocampal degeneration. Animals were sorted into four (n=6), Group I: received corn oil (vehicle) intraperitoneally (i.p.); Group II: received quercetin 50 mg/kg bwt (gavage); Group III: were induced with Aroclor 1254 (commercial mixture of PCB) at 2 mg/kg bwt (i.p); Group IV: received quercetin 50 mg/kg bwt (gavage) and along with PCBs 2 mg/kg bwt (i.p.) for 30 days. Cognitive behaviors such as learning and memory were assessed by 8-arm radial maze behavior test throughout the experimental period. Subsequently, anxiety and stress were studied by open field test at the termination of experiment. Hippocampal tissue and blood were collected after the intended experimental period to analyze the levels of oxidative stressors, antioxidants in tissue and estimation of neurotransmitters. Perhaps, PCBs evoke detrimental deterioration of the neurotransmitters and integrative antioxidant defense by elevation of reactive oxygen species (ROS). Concurrent treatment with quercetin prominently suppresses the oxidative stressors, improved the levels of enzymatic antioxidants and neurotransmitter levels significantly at the level of p<0.05. Behavioral analysis claims drastic revitalization of cognitive functions like learning and memory on treatment with quercetin. The results coalesced depicts neurotoxicity stimulated by PCBs is augmented by simultaneous quercetin administration.

Melatonin attenuates polychlorinated biphenyls induced apoptosis in the neuronal cells of cerebral cortex and cerebellum of adult male rats--in vivo.

Polychlorinated biphenyls (PCBs) are widespread persistent environmental contaminants that display a complex spectrum of toxicological properties, including neurotoxicity. Studies have shown that PCBs increase oxidative stress in brain, leading to apoptosis. The progressive loss of neurons in cerebral cortex and cerebellum, leads to various neurodegenerative diseases. Hence the present study is designed to determine PCBs toxicity toward neuronal cells and whether it could be inhibited by potent antioxidant melatonin. Four groups of adult male Wistar rats were treated for 30 days with corn oil, PCBs, PCBs+Mel and Melatonin, respectively. After treatment period the rats were euthanized and the brain was dissected to isolate cerebral cortex and cerebellum. The neuronal cells alone were then separated from the isolated brain regions, to detect the mRNA levels of apoptotic and neurofilament gene, a neuronal specific marker. Our results suggests that PCBs induces apoptosis in neuronal cells which is subsided by the anti apoptotic effect of melatonin.

Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: impact of alpha-tocopherol.

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg(-1)day(-1) of PCB (i.p.); Group III rats were treated with 2 mg kg(-1)day(-1) of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg(-1)day(-1) of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H(2)O(2)) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-ß in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H(2)O(2) generation, LPO, ER-ß were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.

Oxidative stress modulates membrane bound ATPases in brain regions of PCB (Aroclor 1254) exposed rats: protective role of alpha-tocopherol.

Polychlorinated biphenyls (PCBs) are a class of widely dispersed and environmentally persistent organic compounds. PCBs exhibit a wide range of toxicological effects including neurotoxicity. Vitamin E (alpha-tocopherol) is an important lipid soluble antioxidant placed in a special region of membranes. Large amounts of energy are required to maintain the signaling activities of the cells in the central nervous system (CNS). Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation-induced changes. The aim of this study was to determine the protective role of vitamin E on Aroclor 1254 induced modulation in membrane bound ATPases in brain regions of rats. One group of rats received corn oil as vehicle for 30days as control. The other group of rats were administered Aroclor 1254 at a dose of 2mgkg(-1) bwday(-1) intraperitoneally for 30days. One group of rats received vitamin E (50mgkg(-1) bwday(-1)) orally simultaneously with Aroclor 1254 for 30days. After 30days, the animals were euthanized and the brain was dissected to hypothalamus and hippocampus to determine the following parameters. Hydrogen peroxide (H2O2), Lipid peroxidation (LPO) and the activities of Na+K+-ATPase, Ca2+-ATPase and Mg2+-ATPase were determined. Reduced glutathione (GSH) level was also determined. Activities of all the enzymes were decreased while an increase in H2O2 and LPO were observed in selected brain regions of PCB treated animals. Simultaneous vitamin E treatment in PCB exposed animals restored all the parameters significantly. These results suggest that oxidative stress is involved in the inhibitory effect of PCB (Aroclor 1254) on membrane bound ATPases in selected brain regions. alpha-tocopherol acts against PCB induced neurotoxicity by decreasing oxidative stress.

Ameliorative effect of vitamins (alpha-tocopherol and ascorbic acid) on PCB (Aroclor 1254) induced oxidative stress in rat epididymal sperm.

The aim of this study was to investigate the possible protective role of vitamins on PCB (Aroclor 1254)-induced spermiotoxicity using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups, each group consists of six animals. The control group received corn oil, the second group of rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. The third group of rats were treated with Aroclor 1254 along with alpha-tocopherol (50 mg/kg of bw/day) for 30 days, while the fourth group of rats were treated with Aroclor 1254 along with ascorbic acid (100 mg/kg bw/day) orally for 30 days. Twenty-four hours after the last treatment, control and experimental animals were killed by decapitation. Sperm was collected from the cauda epididymal region and its count and motility were detected. Sperm was sonicated and used for the estimation of reactive oxygen species (ROS) [hydroxyl radical (HO(*)) and hydrogen peroxide (H(2)O(2))], non-enzymic antioxidants [alpha-tocopherol, ascorbic acid and reduced glutathione (GSH)], activity of enzymic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST)] and lipid peroxidation (LPO). The result of this experiment shows that PCB significantly decreases the level of alpha-tocopherol, ascorbic acid and GSH and the activities of SOD, CAT, GPx, GR and GST with elevated levels of ROS and LPO. In addition, decreased epididymal sperm motility and count were observed. Simultaneous supplementation with alpha-tocopherol and ascorbic acid restored these parameters to that of normal range. In conclusion, alpha-tocopherol and ascorbic acid exhibited protective effect on sperm by inhibiting PCB-induced ROS generation.

Effect of 17beta-estradiol on apoptosis, IGF system components and gelatinases A and B in prostate cancer cells (PC-3).

BACKGROUND: Previous studies have indicated that estrogen administration in the advanced stage of prostate cancer provide some benefits to the patients. Estrogen action was thought to be mediated via the blockade of the pituitary-testicular axis that effectively lowered the circulating levels of androgen and, thus, results in tumor regression; however, the effect of estrogens on prostate epithelial cells is still unclear. We investigated the effects of estradiol on insulin-like growth factor type I receptor (IGF-IR), IGF-binding protein 3 (IGFBP-3), IGFBP-4, and matrix metalloproteinase 2 (MMP-2) and MMP-9 in androgen-independent prostate cancer cells (PC-3). METHODS: The cells were treated with different concentrations of estradiol (1, 10 and 100 nmol/l) for different time periods (24, 48, 72 and 96 h). Cell proliferation was assessed using MTT assay, and IGFBP-3 and IGFBP-4 were assessed using immunoradiometric and enzyme immunoassays, respectively. MMP-2, MMP-9 and IGF-IR expression levels were analyzed using western-blot analysis, and MMP-2 and MMP-9 activities were analyzed using gelatin zymography. Apoptosis was confirmed by Annexin V-FITC and acridine orange and ethidium bromide staining methods. DNA fragmentation studies were also performed. RESULTS: Cell proliferation assay revealed that 10 and 100 nmol/l estradiol concentrations inhibit the proliferation of PC-3 cells when incubated for 48-96 h. The secretory levels of IGFBP-3 and IGFBP-4 were increased significantly. The western-blot results showed that estradiol is capable of decreasing the expression of MMP-2 and MMP-9 significantly. Gelatin zymography showed that activities of MMP-2 and MMP-9 are decreased in estradiol-treated cells. Estradiol-induced apoptosis was studied using annexin V-binding and propidium iodide influx. Estradiol also induced nuclear fragmentation in higher doses (100 nmol/l) in PC-3 cells. CONCLUSION: Inhibition of MMPs in cancer cells and increased levels of IGFBP-3 and IGFBP-4 associated with apoptosis may be one of the targets for anticancer function of estradiol. Estradiol inhibits the proliferation of prostate cancer cells by inducing apoptosis.

Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3).

BACKGROUND: Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Quercetin is a flavonoid and widely used as an antioxidant and recent studies have revealed its pleiotropic anticancer and antiproliferative capabilities. Gelatinases A and B (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion and metastases. In this study, we observed the precise involvement of quercetin role on these proteinases expression and activity. DESIGN AND METHODS: PC-3 cells were treated with quercetin at various concentrations (50 and 100 microM), for 24 h period and then subjected to western blot analysis to investigate the impact of quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions. Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin zymography was also performed in quercetin treated PC-3 cells. RESULTS: The results showed that quercetin treatment decreased the expressions of MMP-2 and MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed the decreased activities of MMP-2 and MMP-9 in quercetin treated cells. CONCLUSION: Hence, we speculated that inhibition of metastasis-specific MMPs in cancer cells may be one of the targets for anticancer function of quercetin, and thus provides the molecular basis for the development of quercetin as a novel chemopreventive agent for metastatic prostate cancer.

Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats.

BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats. METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles. CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding protein and lactate in adult rat in vitro.

Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10(-10) to 10(-7) M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), gamma-glutamyl transpeptidase (gamma-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10(-10) to 10(-7) M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.

Drug resistance in tuberculosis in India.

The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs viz., isoniazid and rifampicin. The level of initial drug resistance is an epidemiological indicator to assess the success of the TB control programme. Though drug resistance in TB has frequently been reported from India, most of the available information is localized, sketchy or incomplete. A review of the few authentic reports indicates that there is no clear evidence of an increase in the prevalence of initial resistance over the years. However, a much higher prevalence of acquired resistance has been reported from several regions, though based on smaller numbers of patients. A strong TB control programme and continuous surveillance studies employing standardized methodology and rigorous quality control measures will serve as useful parameters in the evaluation of current treatment policies as well as the management of multidrug resistant (MDR) TB cases.

Effects of vitamin supplementation on PCB (Aroclor 1254)-induced changes in ventral prostatic androgen and estrogen receptors.

The objective of this study was to determine the impact of the polychlorinated biphenyl (PCB) Aroclor 1254 and vitamin C and E on ventral prostatic testosterone and estradiol receptor concentration. A group of 30 rats were treated with Aroclor 1254 [2 mg/kg body weight (bwt) /day/ip] for 30 days; 10 rats were treated as Aroclor 1254 control. The remaining 20 rats were subdivided into the following two subgroups of 10 animals each. One group was given vitamin C (500 mg/kg bwt/day/oral) for 10 days, whereas the other group was given vitamin E (50 mg/kg bwt/day/oral) for 10 days. Separate controls were also maintained. Ventral prostatic androgen and estrogen receptor concentration in all the groups were quantified. Serum hormonal profiles such as total T3, T4, TSH, testosterone, and estradiol were also estimated in all the groups. Ventral prostatic zinc content and serum zinc concentration were also determined in all the groups. Aroclor 1254 exposure decreased the concentration of both receptors. Decreased serum total T3, T4, testosterone, estradiol, and increased TSH were observed after Aroclor 1254 exposure. Serum and tissue zinc levels were also decreased. Administration of vitamin C or E restored both the receptor concentration and the serum hormone levels with the exception of estradiol. Administration of vitamin C or E restored zinc levels. Vitamin E was more sensitive on ventral prostatic androgen receptors and zinc levels, including serum, in PCB-exposed rats.

Antioxidant role of zinc in PCB (Aroclor 1254) exposed ventral prostate of albino rats.

The ability of zinc to retard oxidative processes has been recognized for many years. Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous study has indicated that PCBs can have deleterious effects, including oxidative stress, on various aspects of reproduction in male rats. The aim of this study was to determine the antioxidant role of zinc in PCB-exposed ventral prostate of albino rats. A group of 20 rats were treated with Aroclor 1254 (2 mg/kg body weight/day, i.p.) for 30 days. After the PCB treatment, 10 rats were treated as PCB control. The remaining 10 rats were given zinc (Zn SO(4)) (200 mg/kg body weight/day, p.o.) for 10 days. Ventral prostatic enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were estimated in all the groups. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and ventral prostatic acid phosphatase (ACP) were also estimated. Serum hormonal profiles such as total tri-iodothyronine (T(3)), thyroxine (T(4)), thyroid stimulating hormone (TSH), testosterone, and estradiol were estimated. Ventral prostatic androgen and estrogen receptors, ventral prostatic zinc content, and serum zinc concentration were also quantified in all the groups. Antioxidant enzymes such as SOD, CAT, GPx, GST, and ACP were decreased while an increase in H(2)O(2) and LPO were observed in PCB-treated animals. Decreased serum total T(3), T(4), testosterone, estradiol and increased TSH were observed in PCB-exposed rats. Ventral prostatic androgen and estrogen receptors were also decreased significantly in PCB-exposed rats. Zinc administration restored to previous levels all parameters except ventral prostatic ACP. These results suggest that PCB induces oxidative stress in rat ventral prostate by decreasing the levels of antioxidant enzymes; the effects could be reversed by the administration of zinc. The adverse effect of PCBs (Aroclor 1254) and zinc on ventral prostate might be due to indirect action through hormonal regulation.