PHYTOPHENOLICS COMPOSITION, HYPOLIPIDEMIC, HYPOGLYCEMIC AND ANTIOXIDATIVE EFFECTS OF THE LEAVES OF FORTUNELLA JAPONICA (THUNB.) SWINGLE

Objective: Fortunella japonica (Thunb.) Swingle is an evergreen shrub, its whole fruit, including the peel, is eaten. There have been few detailed phytophenolics composition reports on this genus and the hypoglycemic and hypolipidemic effects of the plant were not evaluated. Methods: Structures of the isolated compounds were elucidated by spectral analysis. Serum glucose level, activities of liver enzymes, total protein content, serum lipid profiles, antioxidant parameters and some glycolytic and gluconeogenic enzymes in streptozotocin (STZ)-induced diabetic rats were determined. The evaluation also carried out through determination of liver disorder biomarkers and histopathological examination of liver, kidney and pancreas. Results: Six phytophenolics were isolated, for the first time from the genus Fortunella as well as a sterol compound. Treatment with the ethanolic extract of F. japonica leaves effectively meliorated antioxidant markers and glycolytic enzymes. The histopathological analyzes also confirmed the experimental findings.Conclusion: The results show that the ethanolic extract has hypoglycemic, hypotriglyceridemic and antioxidant effects in STZ-induced diabetic rats, suggesting that this extract supplementation can be useful in preventing diabetic complications associated with hyperlipidemia and oxidative stress.Â

Evaluation of Protective and Antioxidant Activity of Thyme (Thymus Vulgaris) Extract on Paracetamol-Induced Toxicity in Rats

Abstract: Paracetamol is a common analgesic and antipyretic drug which is safe in therapeutic doses but can produce life-threatening hepatic and renal damages with toxic doses. The current study was designed to investigate the protective effects of aqueous extract of thyme (Thymus Vulgaris) against paracetamol-induced toxicity in male albino rats. A total of 24 rats were used for the study. The rats were grouped into four with sex rats in each group. Group I was the control, group II received thyme extract at a dose of 500 mg / kg body weight for 14 days. group III received paracetamol at a dose of 200 mg / kg body weight / ml without extract for 14 days, and group IV received paracetamol plus thyme extract for 14 days. Administration of paracetamol to rats induced marked disturbance of hepatic and renal functions, characterized by a significant increase in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP),total bilirubin , total protein , blood urea and serum creatinine (p < 0.01) and injured the hepatic and renal cells evident from increased level of malondialdehyde (MDA) (p < 0.01) along with depletion of super oxide dismutase (SOD), catalase (CAT), activities and reduced glutathione (GSH) levels (p < 0.01). Histopathological changes showed that paracetamol caused significant structural damages to liver and kidneys. Oral co-administration of thyme extract with paracetamol significantly decreased the level of liver enzymes (ALT, AST and ALP), total bilirubin , total protein, blood urea and creatinine. The increased levels of lipid peroxidation in tissues were reverted significantly. Thyme treatment also resulted in a significant increased in CAT, SOD and GSH in both liver and kidneys. Moreover, thyme extract also exhibited some improvement in the histological architecture of liver and kidney . These results clearly show the antioxidant and protective property of thyme extract

Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy