Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat

BMJ Open

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative : study protocol and rationale of a multicentre retrospective individual patient data meta-analysis

Introduction Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Peer reviewe

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults

ObjectivesWe examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association.Materials and MethodsThis prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura.ResultsAfter adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS.ConclusionsAbdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.</p

Image-guided Keyhole Evacuation of Spontaneous Supratentorial Intracerebral Hemorrhage

WOS: 000266245800002PubMed ID: 19452411Introduction: Treatment of spontaneous supratentorial intracerebral hemorrhage (SICH) is controversial. This study aims to evaluate the outcome and invasiveness of one surgical approach that provides complete evacuation of SICH, the image-guided keyhole evacuation. Methods: The technique was employed in 20 consecutive patients, nine of whom harbored deep hematomas. The hematoma was evacuated through a keyhole minicraniotomy, 2.5 cm in diameter. Computerised tomographic (CT) scan was performed at the end of the procedure to confirm completeness of evacuation. Invasiveness was assessed by comparing initial neurological status determined by Glasgow Coma Scale (GCS) scores and National Institutes of Health Stroke Scale (NIHSS) scores with the third and seventh postoperative day scores, and by radiological findings. Outcome at six months was assessed by the Extended Glasgow Outcome Scale, and by comparing the initial and 6 month modified Rankin Scale scores. Results: Mean age was 63.7 +/- 14.8 years, mean volume was 41.6 +/- 17.5 mL, and mean time to surgery was 17.6 +/- 13.2 h. CT scans at the end of the procedure showed complete evacuation (mean 97.5%), and 60% decrease of both mean midline shift and mean edema volume (p=0.005). Neurological assessment at the end of the first postoperative week showed significant improvement (p<0.0001). At six months, 90% of the patients had achieved recovery to independence, and one patient had died. Conclusion: The image-guided keyhole approach allowed prompt evacuation of SICH and resulted in a high rate of functional recovery and low mortality. This is a minimally invasive technique that is highly effective in immediate and complete hematoma evacuation

Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity

Objectives: Chronic consumption of high-fructose corn syrup (HFCS) causes several problems such as insulin resistance. The goal of the study was to investigate pancreatic damage induced by chronic HFCS consumption and the protective effects of alpha lipoic acid (ALA) on pancreatic cells.Methods: Wistar Albino, 4-month-old, female rats weighing 250-300 g were randomly distributed into three groups, each containing eight rats. The study included an HFCS group, an HFCS + ALA-administered group and a control group (CON). The prepared 30% solution of HFCS (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks. ALA treatment was begun 4 weeks after the first HFCS administration (100 mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical dislocation 24 h after the last ALA administration. Blood samples for biochemical tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue samples for histopathological and immunohistochemical examinations (caspase-3, insulin and glucagon) were collected.Results: Comparing the control and HFCS groups, serum glucose (150.92 +/- 39.77 and 236.50 +/- 18.28, respectively, p < 0.05), amylase (2165.00 +/- 150.76 and 3027.66 +/- 729.19, respectively, p < 0.01), lipase (5.58 +/- 2.22 and 11.51 +/- 2.74, respectively, p < 0.01) and pancreatic tissue MDA (0.0167 +/- 0.004 and 0.0193 +/- 0.006, respectively, p < 0.05) levels were increased, whereas tissue CAT (0.0924 +/- 0.029 and 0.0359 +/- 0.023, respectively, p < 0.05) activity decreased in the HFCS group significantly. Histopathological examination revealed degenerative and necrotic changes in Langerhans islet cells and slight inflammatory cell infiltration in pancreatic tissue in the HFCS group. Immunohistochemically there was a significant decrease in insulin (2.85 +/- 0.37 and 0.87 +/- 0.64, respectively, p < 0.001) and glucagon (2.71 +/- 0.48 and 1.00 +/- 0.75, respectively, p < 0.001) secreting cell scores, whereas a greater increase in caspase-3 (0.14 +/- 0.37 and 1.00 +/- 0.75, respectively, p < 0.05) expression was seen in this group compared with the controls. In the ALA-treated group, all of these pathologic conditions were improved.Conclusions: This study indicated HFCS induced pancreatic lesions, but ALA had ameliorative effects. (C) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved