Neuroprotective and hepatoprotective effect of whole red rice forms against oxidative stress in streptozotocin induced diabetic rats.

151-160Whole red rice (Oryza sativa L.), consumed as staple food in many countries worldwide, is rich in phytochemicals, mainly antioxidants having health potency. The present study evaluated the neuro- and hepatoprotective efficacy of raw and parboiled whole red rice against streptozotocin (STZ) induced oxidative stress, and antioxidant metabolism both in diabetic and normal non-diabetic rats. Wistar rats were rendered diabetic by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg body wt.), supplemented with raw and parboiled whole red rice for six weeks. Results revealed a drastic increase in oxidative stress markers, such as lipid peroxidation, nitric oxide (NO) level, hydroperoxide (HP) level; antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), thioredoxin reductases (TR), glutathione S-transferase (GST), acetylcholinesterase (AChE) activity, and decrease in endogenous antioxidant, glutathione (GSH) in diabetic rat. On the other hand, addition of raw and parboiled whole red rice in the diet counteracted the STZ induced oxidative stress in diabetic groups and improved the neuro and hepatic antioxidant system. Both, parboiled and raw red rice forms, exercised similar impacts in diabetic as well as in normal rats suggesting improved antioxidant defence mechanism. Results have shown that the whole red rice possess antidiabetic potential with the antioxidant improving ability, and could be utilized as dietary supplements in diabetes management

Nutrients, Nutraceuticals and Bioactive Properties of Multi-Whole Grain Mix for Drink and Porridge

Whole grains are reported to be rich in nutrients, nutraceuticals and have number of health beneficial effects. A convenient multi-whole grain mix for the preparation of a drink or porridge was formulated by using cereals, millets, pulses and nuts. Particle size was mostly of 180-250 microns (52%). Amylograph characteristics like GT, PV, HPV, CPV were 82°C, 285BU, 310BU, and 605BU, respectively were ideal for drink. The mix was found to be rich in carbohydrate, protein, fibre and calorie. The 100g of the mix had nutraceuticals like carotenoids (290µg), γ-tocopherol (4.6mg), α-tocopherol (1.5mg), and polyphenols-soluble, bound and total (94,132 and 226mg GA Eq.). Bioactive properties like vitamin E activity, free radical scavenging activity, total antioxidant activity and starch digestibility were 2.6i.u., 153mg catechin.Eq./100g, 17mg Tocopherol equivalent and 61.8%. Mix was sensorily acceptable in the form of drink and porridge and can be used as an ideal nutritious food for all age group

LIQUID LAYERING AND THE ENHANCED THERMAL CONDUCTIVITY OF Ar-Cu NANOFLUIDS: A MOLECULAR DYNAMICS STUDY

ABSTRACT Nanofluids -colloidal suspensions of nanoparticles in base fluids -are known to possess superior thermal properties compared to the base fluids. Various theoretical models have been suggested to explain the often anomalous enhancement of these properties. Liquid layering around the nanoparticle is one of such reasons. The effect of the particle size on the extent of liquid layering around the nanoparticle has been investigated in the present study. Classical molecular dynamics simulations have been performed in the investigation, considering the case of a copper nanoparticle suspended in liquid argon. The results show a strong dependence of thickness of the liquid layer on the particle size, below a particle diameter of 4nm. To establish the role of liquid layering in the enhancement of thermal conductivity, simulations have been performed at constant volume fraction for different particle sizes using Green Kubo formalism. The thermal conductivity results show 100% enhancement at 3.34% volume fraction for particle size of 2nm. The results establish the dominant role played by liquid layering in the enhanced thermal conductivity of nanofluids at the low particle sizes used. Contrary to the previous findings, the molecular dynamics simulations also predict a strong dependence of the liquid layer thickness on the particle size in the case of small particles. Nomenclature U Interatomic potentia

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper

Alcohol consumption and the risk of morbidity and mortality for different stroke types - a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Observational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention.</p> <p>Methods</p> <p>Using Medical Subject Headings (alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke), a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science databases between 1980 to June 2009 was performed followed by manual searches of bibliographies of key retrieved articles. From twenty-six observational studies (cohort or case-control) with ischemic or hemorrhagic strokes the relative risk or odds ratios or hazard ratios of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and life time abstention (manually estimated where data for current abstainers were given) was used as the reference group. Two reviewers independently extracted the information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, risk estimates and key criteria of study quality using a standardized protocol.</p> <p>Results</p> <p>The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity.</p> <p>Conclusions</p> <p>These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed.</p

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

<p>Abstract</p> <p>Background</p> <p>In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.</p> <p>Methods</p> <p>A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.</p> <p>Results</p> <p>There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.</p> <p>Conclusion</p> <p>The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.</p

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management