Studies on protein characteristics and toxic constituents of Simarouba glauca oilseed meal

In order to exploit the protein rich (47.7 g/100 g) simarouba meal in food/feed, studies were conducted on its chemical composition with emphasis on protein characteristics and toxic constituents. Simarouba meal contained high calcium (143 mg/100 g) and sodium (79 mg/100 g). Saponins with triterpenoid aglycone (3.7 g/100 g), alkaloids (1.01 g/100 g), phenolics (0.95 g/100 g) and phytic acid (0.73 g/100 g) were the major toxic constituents identified in simarouba meal. TLC and HPLC results indicated that among different fractions of simarouba saponins, one dominant fraction accounted for about 28%. Proteins of simarouba recorded high in vitro digestibility (88%). SDS–PAGE revealed four major protein bands in molecular weight ranges of 20–24, 36–45 and 55–66 kDa. Apart from, glutamic acid (23.43 g/100 g protein) and arginine (10.75 g/100 g protein), simarouba protein contained high essential amino acids like leucine (7.76 g/100 g protein), lysine (5.62 g/100 g protein) and valine (6.12 g/100 g protein). Among nutritional indices, simarouba meal recorded a good EAA Index (75.02), C-PER (1.90) and PDCAAS (1.0-Adult group).     

Downregulation of endothelial nitric oxide synthase in rat aorta after prolonged hypoxia in vivo

The goal of this study was to determine whether hypoxia alters expression of endothelial nitric oxide synthase (eNOS) in the systemic circulation. Rats breathed either air or 10% oxygen for 12 hours, 48 hours, or 7 days. Thoracic aortas were excised and either mounted in organ bath myographs or frozen in liquid nitrogen for later extraction of protein and RNA. eNOS protein (Western blotting) was decreased (20% of normoxic control) after 12 hours, 48 hours, and 7 days of hypoxia. eNOS mRNA (ribonuclease protection assay) was similarly reduced. Acetylcholine (10(-4) mol/L) reversed phenylephrine (10(-5) mol/L) preconstriction by 53.3+/-5.6% in aortic rings from normoxic rats and 26.1+/-4.8% in rings from rats exposed to hypoxia for 48 hours (P<0.05), with comparable impairment of relaxation by the calcium ionophore A23187 (10(-5) mol/L). Responses to diethylamine nitric oxide and 8-bromo-cGMP were unaffected. Aortic cGMP levels after incubation with acetylcholine (10(-6) mol/L) averaged 14.0+/-1.8 fmol/mg in rings from normoxic rats compared with 8.7+/-1.0 fmol/mg in rings from hypoxic rats (P<0. 05). Similarly, nitrate concentration (by capillary electrophoresis) in the media in which the rings were incubated was reduced in the hypoxic group (5.6+/-0.23 micromol/L for hypoxic rats and 7.8+/-0.7 micromol/L for normoxic rats). Impaired endothelial NO release may handicap the vascular responses that defend vital organ function during hypoxia.     

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

Background

Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span.

Methods

We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001).

Results

In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10^-5). The two sets of SNPs were in high linkage disequilibrium (minimum r² = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.

Conclusion

Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

     

In vivo antidiabetic activity and in silico studies on adenosine monophosphate-activated protein kinase (AMPK) of (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone

Effect of bischalcone derivative (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone (CA) on blood glucose level and lipid profile was investigated in normoglycemic and streptozotocin (STZ)-induced diabetic rats. In oral glucose and sucrose tolerance test, treatment with CA (25 mg/kg) and glidenclamide (10 mg/kg) significantly improved the glucose and sucrose tolerance in normal animals. In addition, respective treatment for 7-day resulted in significant percentage reduction in serum glucose (SG). In standardized STZ-induced diabetic rats, a single dose of CA treatment exhibited reduction in SG levels at different time intervals compared to basal levels. The lipid profile levels are restored to near-normal value of all tested parameters. The compound CA was docked into the active site of 5′-AMP (adenosine monophosphate)-activated protein kinase (PDB ID: 2OOX). The binding and docking energy were found to be ?6.9 and ?45.1 kcal/mol, respectively.     

Protective effect of Gymnema montanum against renal damage in experimental diabetic rats

Gymnema montanum Hook (Asclepiadaceae), is an endemic plant species of India, traditionally used for diabetes and its management. In this experiment, the ethanol extract of G. montanum (GLEt) at a dose of 200 mg/kg body weight was tested to evaluate its effect on renal damage in alloxan-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide (600 μg/kg body weight). The GLEt and glibenclamide were administered orally for 3 weeks and the effects on glucose, insulin, renal markers including urea, creatinine and uric acid, lipid peroxidation markers including thiobarbituric reactive substances (TBARS) and hydroperoxides and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in kidney were studied. In addition, the urinary protein profile was studied using SDS–PAGE. The results indicated that the GLEt significantly normalized the elevated blood glucose, renal markers and lipid peroxidation markers and increased antioxidant levels in diabetic kidney. The diabetic rats excreted large amount of proteins than untreated rats which was normalized during the treatment with GLEt. In conclusion, the GLEt was found to be more effective in reducing oxidative stress, thus confirming the ethnopharmacological use of G. montanum in protecting diabetes and its complications.     

Studies on radioprotective and antiviral activities of some bischalcone derivatives

This work reports the cyclic voltammetric, modulatory effect on oxidative stress markers against radiation induced oxidative stress in E. coli bacteria and antiviral activities of two bischalcone derivatives (2E,5E)-2,5-bis(3-methoxy-4-hydroxy-benzylidene)-cyclopentanone (B1) and (2E,5E)-2,5-bis(4-fluorobenzylidene)-cyclopentanone (B2). The reducing ability of B1 and B2 was determined by cyclic voltammetry. The anodic peak current i _pa and anodic peak potential Epa of B1 and B2 were ?154.7, ?99?μA, and ?0.15?V, 0.0125?V, respectively. The low anodic current and low anodic peak potential imply the good reducing ability of the molecules. The radioprotective effect of bischalcones was studied by gamma radiation induced oxidative stress in E. coli K12 at 0.2 and 0.4?Gy. The bacteria samples treated with B1 and irradiated showed diminished level of TBARS, an oxidative stress marker. The levels of SOD and CAT antioxidant enzymes were brought to near basal level for B1 treated and irradiated bacteria with respect to the control. The protective effect of the bischalcone derivatives against radiation was further supported by determining colony forming units (CFU) of bacteria in pre- and post-irradiated samples. Further, B2 showed 73.69% of inhibition of buffalopox virus and camelpox virus.     

Coronary Artery Embolism: Two Case Reports and a Review of the Literature

Coronary embolism (CE) is an uncommon and unique cause of acute myocardial infarction. In this report, we review 216 cases of CE including 2 new cases from our institution. The mean patient age was 52.5 years and 62% of the patients were males. Chest pain was the most common presenting symptom followed by dyspnea, and the most commonly affected vessel was the left anterior descending artery. Leading etiologies of the embolus were atrial fibrillation, septic emboli, and iatrogenic causes. Treatment approaches varied with thrombus aspiration being used in 30% of cases. In-hospital mortality rate was 36% and 13% of the cases were complicated by cerebrovascular accident. CE is a unique pathology that leads to acute myocardial infarction. It portends a high mortality rate and requires a high level of suspicion as symptoms may be misleading. Further research is needed in order to improve recognition and management and to lower associated mortality.