Synergistic effects of squalene and polyunsaturated fatty acid concentrate on lipid peroxidation and antioxidant status in isoprenaline-induced myocardial infarction in rats

We have studied the synergistic effects of squalene and polyunsaturated fatty acids (PUFA concentrate) on isoprenaline-induced infarction in rats with respect to changes in the levels of plasma diagnostic marker enzymes and myocardial antioxidant defense system. Intraperitoneal injection of isoprenaline caused a significant elevation in the levels of diagnostic marker enzymes; alanineaminotranferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in plasma of experimental rats. There was a significant rise in the level of lipidperoxidation with concomitant decline in the level of reduced glutathione (GSH) and in the activities of glutathione-dependent antioxidant enzymes; glutathione peroxidase (GPX) and glutathione-Stransferase (GST), and antiperoxidative enzymes; superoxide dismutase (SOD) and catalase (CAT) in heart tissue. Combined supplementation of squalene and PUFA concentrate significantly prevented the isoprenaline-induced elevations in the levels of diagnostic marker enzymes in plasma of experimental groups of rats. A tendency to counteract the isoprenaline induced lipid peroxidation was also noticed. Their combined administration maintained the level of GSH and the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes at near normalcy. The results of the present study indicated that the combined administration of squalene and PUFA concentrate exerted significantly better cardio-protection against isoprenaline-intoxication as compared to that of per secondsupplementation

Assessment of genetic diversity among Malnad Gidda, Punganur and Vechur-dwarf cattle breeds of India using microsatellite markers

The genetic diversity among 3 dwarf breeds of cattle in India, viz. Malnad Gidda, Punganur and Vechur were analysed using 12 sets of microsatellite markers. All 11 amplified microsatellite loci were polymorphic with a mean number of alleles of 7.818±1.66 across breeds and in different breeds it ranged from 7.273 in Malnad Gidda to 3.546 in Vechur. The mean polymorphic information content (PIC) value observed and expected heterozygosity values across the population were 0.642, 0.610 and 0.683, respectively. A moderate level of inbreeding was observed with the inbreeding estimates ranging from -0.027 (ILSTS6) to 0.271 (HAUT24). Among the 3 breeds the highest mean number of alleles (7.273), mean PIC value (0.639), observed heterozygosity (0.630) and lower inbreeding estimates at majority of loci were observed in Malnad Gidda cattle indicating high degree of heterozygosity compared to Punganur and Vechur breeds. Even though departure from Hardy Weinberg Equilibrium (HWE) was found in Vechur and Punganur cattle population at majority of the loci, the population combining the 3 breeds was maintained at HWE with respect to most of loci under study. The genetic distance analysis revealed highest genetic distance between Vechur and Punganur (0.331) and lowest between Malnad Gidda and Punganur (0.125)

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

<p>Abstract</p> <p>Background</p> <p>11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet) on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats.</p> <p>Methods</p> <p>Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype) were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided <it>ad libitum</it>. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat.</p> <p>Results</p> <p>Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα), the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα), a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes.</p> <p>Conclusions</p> <p>This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly contribute to visceral fat loss in these obese rats. Studying the role of various nutrients on the regulation of 11β-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance.</p

Algorithm Engineering in Robust Optimization

Robust optimization is a young and emerging field of research having received a considerable increase of interest over the last decade. In this paper, we argue that the the algorithm engineering methodology fits very well to the field of robust optimization and yields a rewarding new perspective on both the current state of research and open research directions. To this end we go through the algorithm engineering cycle of design and analysis of concepts, development and implementation of algorithms, and theoretical and experimental evaluation. We show that many ideas of algorithm engineering have already been applied in publications on robust optimization. Most work on robust optimization is devoted to analysis of the concepts and the development of algorithms, some papers deal with the evaluation of a particular concept in case studies, and work on comparison of concepts just starts. What is still a drawback in many papers on robustness is the missing link to include the results of the experiments again in the design

Calcium-Rich Pigeonpea Seed Coat: A Potential Byproduct for Food and Pharmaceutical Industries

Pigeonpea is a protein-rich legume which is consumed worldwide in a variety of forms (whole seed, dhal, and as a green vegetable). In India, pigeonpea is milled to yield dhal (cotyledon) and this process generates 25–35% waste byproducts. The hull (seed coat) which accounts for 10% of the byproduct is disposed of either as waste or low-cost cattle feed. To recycle the waste byproducts into the food value chain, this study was conducted with the objectives: (i) to estimate nutrient accumulation in the major seed fractions (cotyledon and seed coat), (ii) to estimate the percentage of nutrient contribution by major seed fractions, (iii) to assess the percentage of nutrient loss due to dehulling, and (iv) to determine the scope of seed coat in nutritional value addition. For this, a subset of 60 diverse pigeonpea accessions selected from 600 pigeonpea accessions raised during the 2019 and 2020 rainy seasons at ICRISAT, Patancheru, India, was subjected to a cotyledon and seed coat nutrient analysis. The three-way analysis of variance revealed the significant influence of cropping years, seed fractions, genotypes, and their interactions on nutrient accumulation. The nutrients, namely protein (32.28 ± 2.29%), P (476.51 ± 39.05 mg/100 g), K (1557.73 ± 66.82 mg/100 g), Fe (4.42 ± 0.41 mg/100 g), Zn (2.25 ± 0.21 mg/100 g), and Cu (0.95 ± 0.07 mg/100 g) were enriched in cotyledon. Mn was equally enriched in both the cotyledon and seed coat (1.02 ± 0.12 mg/100 g and 0.97 ± 0.34 mg/100 g, respectively). The seed coat had a high concentration of Ca (652.02 ± 114.82 mg/100 g), and Mg (249.19 ± 34.12 mg/100 g) with wide variability for Fe (2.74–5.61 mg/100 g), Zn (0.88–3.95 mg/100 g), Cu (0.38–1.44 mg/100 g), and Mn (0.58–2.18 mg/100 g). It is noteworthy that the protein and P contents in the cotyledon were 7 and 18 times higher than that in the seed coat, respectively, and the Ca content in the seed coat was 12 times higher than that in the cotyledon. A correlation study revealed that for overall nutrient improvement in dhal, selection for a small seed size was desirable. On an average, the percentage of nutrient contribution by major seed fractions revealed that the cotyledon portion contributed around 95% protein and P; 90% K and Zn; 85% Fe, Cu, and Mn; and 75% Mg, while the seed coat portion contributed nearly 65% Ca to the whole grain. The findings of high Fe and protein concentrations in the cotyledon and high Ca accumulation in the seed coat can serve as a new guide for improved technological fractionation of these components to serve as a novel functional food ingredient and as a dietary supplement that can address malnutrition

Isofagomine In Vivo Effects in a Neuronopathic Gaucher Disease Mouse

The pharmacological chaperone, isofagomine (IFG), enhances acid β-glucosidase (GCase) function by altering folding, trafficking, and activity in wild-type and Gaucher disease fibroblasts. The in vivo effects of IFG on GCase activity, its substrate levels, and phenotype were evaluated using a neuronopathic Gaucher disease mouse model, 4L;C* (V394L/V394L + saposin C-/-) that has CNS accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) as well as progressive neurological deterioration. IFG administration to 4L;C* mice at 20 or 600 mg/kg/day resulted in life span extensions of 10 or 20 days, respectively, and increases in GCase activity and protein levels in the brain and visceral tissues. Cerebral cortical GC and GS levels showed no significant reductions with IFG treatment. Increases of GC or GS levels were detected in the visceral tissues of IFG treated (600 mg/kg/day) mice. The attenuations of brain proinflammatory responses in the treated mice were evidenced by reductions in astrogliosis and microglial cell activation, and decreased p38 phosphorylation and TNFα levels. Terminally, axonal degeneration was present in the brain and spinal cord from untreated and treated 4L;C* mice. These data demonstrate that IFG exerts in vivo effects by enhancing V394L GCase protein and activity levels, and in mediating suppression of proinflammation, which led to delayed onset of neurological disease and extension of the life span of 4L;C* mice. However, this was not correlated with a reduction in the accumulation of lipid substrates

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid βâ glucosidase), with consequent cellular accumulation of glucosylceramide (GLâ 1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GLâ 1 storage in the liver, spleen, and lung of 3â monthâ old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genzâ 112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genzâ 112638 showed the lowest levels of GLâ 1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GLâ 1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genzâ 112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147062/1/jimd0281.pd