Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome

Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Treatment of milk wastewater using up-flow anaerobic packed bed reactor

An up-flow anaerobic packed bed (UAPB) bioreactor has been designed on a laboratory-scale and used for treatment of domestic milk wastewater (MWW). The UAPB bioreactor was operated under mesophilic temperature (37-45°C) and reactor performance evaluated at various organic loading rates of MWW effluent at hydraulic retention times (HRT) of 1, 2, and 3 d based on the removal of organic matter COD, BOD, SS, pH changes and biogas production. The kinetic parameters were estimated using the experimental data to develop a reactor model. Empirical relations were generated for the characteristics like COD, BOD, and SS using modeling equations. This study proved that the UAPB reactor performance is excellent for treating domestic MWW and easily biodegradable dairy wastewater influent. Hence, this system can operate at low costs, making it suited for use in the developing countries and rural areas

Ambazari lake water treatment using hybrid membrane bioreactor and nanofiltration system

Advanced water treatment methods are needed for good quality of lake water. In this study, the hybrid membrane bioreactor (MBR) and nanofiltration (NF) system was investigated to treat Ambazari lake water. The performance of the hybrid system was checked as removal efficiency of chemical oxygen demand (COD), total dissolved solids (TDS), biochemical oxygen demand (BOD), and permeate flow rate (PFR). All parameters in the hybrid MBR-NF system were operated batch-wise for 5 h. The COD and BOD removal efficiencies were observed to be 95.67 % and 94.64 %, respectively. TDS removal efficiency was obtained to be 92.33%. The highest TSS removal efficiency was reported to be 36.0 % for airflow rates of 1.0 L/min. The pH variation at different airflow rates was found to be significantly low. Hence, from above information, we conclude that this hybrid system treated Ambazari lake water successfully. The treated water had high quality as good as potable water

Immunotoxicity of phosphamidon following subchronic exposure in albino rats

316-320Effect 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

Xenobiotic-induced Immune Alterations: Implications in Health and Disease

7-15Immune function may be significantly altered following occupational, inadvertent or therapeutic exposure to chemically diverse xenobiotics. The environmental chemicals like pesticides, halogenated hydrocarbons, polychlorinated dibenzofurans, organic solvents, asbestos, silica, heavy metals etc. may interact with both cellular and humoral components of the immune system which can result in altered immune status that in turn may lead to decreased resistance to infection, certain forms of neoplasia or in some cases exacerbate allergy or autoimmunity. Recent advances in pharmacogenomics and toxicogenomics have contributed a lot to delineate the mechanism of interaction of xenobiotics with the biological system at the cellular and molecular level. However, detection of immune changes on exposure to immunotoxic agents is highly complex, especially in humans due to several confounding factors like age, sex, race gender, co- existence of disease, food habits, smoking etc. Thus, establishing a quantitative relationship between immunotoxicological data and risk assessment, following xenobiotic exposure is still a challenge. The present article reviews the immune alterations caused by exposure to variety of xenobiotics, and their implications in health and disease

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

278-281The 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-α and IFN-γ levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-α and IFN-γ 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

Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: Attenuation by <i>Withania somnifera</i>

117-120Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immuno-modulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur

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

312-315Effect 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