Student forum: Does calcium and vitamin D intake affect incidence of type 2 diabetes mellitus and insulin resistance syndrome?

The past few decades have seen an enormous increase in the incidence of type 2 diabetes mellitus (T2DM). Hyperinsulinemia, hypertension, abdominal obesity, dyslipidemia, and coagulation abnormalities-which contribute to insulin resistance syndrome-are major risk factors for T2DM and heart disease. Diet plays an important role in prevention of these risk factors.

Antioxidants in central nervous system diseases: preclinical promise and translational challenges.

Oxidative damage is strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and stroke (brain ischemia/reperfusion injury). The availability of transgenic and toxin-inducible models of these conditions has facilitated the preclinical evaluation of putative antioxidant agents ranging from prototypic natural antioxidants such as vitamin E (alpha-tocopherol) to sophisticated synthetic free radical traps and catalytic oxidants. Literature review shows that antioxidant therapies have enjoyed general success in preclinical studies across disparate animal models, but little benefit in human intervention studies or clinical trials.

Identification of lanthionine synthase C-like protein-1 as a prominent glutathione binding protein expressed in the mammalian central nervous system.

Proteomic experiments were performed to identify novel glutathione (GSH) binding proteins expressed in the mammalian central nervous system. Bovine brain lysate was affinity purified using an immobilized glutathione-Sepharose column. Proteins that bound the immobilized glutathione were eluted with free glutathione and identified by one- and two-dimensional electrophoresis coupled with mass spectrometric analysis of tryptic fragments.

On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis.

The central nervous system (CNS) presents both challenges and opportunities to researchers of redox biochemistry. The CNS is sensitive to oxidative damage during aging or disease; excellent transgenic models of specific neurodegenerative diseases have been created that reproduce oxidative stress components of the corresponding human disorder. Mouse models of familial amyotrophic lateral sclerosis (ALS) based on overexpressed mutant human Cu, Zn-superoxide dismutase (SOD1) are cases in point.

Chronic thrombin exposure results in an increase in apolipoprotein-E levels.

Studies have shown that individuals with both a history of traumatic brain injury and inheritance of apolipoprotein E-4 (ApoE4) allele are associated with a poor neurologic outcome and an increased risk for Alzheimer's disease. We assessed the hypothesis that thrombin released during brain injury causes an increase in apolipoprotein-E levels and such increase in the levels of apolipoprotein-E4 isoform may have amyloidogenic effects. Rats received either thrombin (100 nm, 0.

Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation.

Detailed study of glial inflammation has been hindered by lack of cell culture systems that spontaneously demonstrate the "neuroinflammatory phenotype". Mice expressing a glycine --> alanine substitution in cytosolic Cu, Zn-superoxide dismutase (G93A-SOD1) associated with familial amyotrophic lateral sclerosis (ALS) demonstrate age-dependent neuroinflammation associated with broad-spectrum cytokine, eicosanoid and oxidant production. In order to more precisely study the cellular mechanisms underlying glial activation in the G93A-SOD1 mouse, primary astrocytes were cultured from 7 day mouse neonates.

The arachidonic acid 5-lipoxygenase inhibitor nordihydroguaiaretic acid inhibits tumor necrosis factor alpha activation of microglia and extends survival of G93A-SOD1 transgenic mice.

Familial forms of amyotrophic lateral sclerosis (ALS) can be caused by mutations in copper, zinc-superoxide dismutase (SOD1). Mice expressing SOD1 mutants demonstrate a robust neuroinflammatory reaction characterized, in part, by up-regulation of tumor necrosis factor alpha (TNFalpha) and its primary receptor TNF-RI. In an effort to identify small molecule inhibitors of neuroinflammation useful in treatment of ALS, a microglial culture system was established to identify TNFalpha antagonists.

Thrombin, a mediator of neurotoxicity and memory impairment.

Thrombin has been found in neuritic plaques in Alzheimer's disease (AD). Also, traumatic brain injury, where neurons are exposed to high thrombin levels, is associated with an increased incidence of AD. Our objective was to determine the effects of thrombin administered in vivo on cognitive function and neuropathology.

5-HT3 antagonist ICS 205-930 enhances naltrexone's effects on ethanol intake.

Opioid receptor antagonist naltrexone has shown some efficacy in decreasing ethanol consumption in humans. However, naltrexone treatment is not always efficacious and produces several aversive effects such as nausea, anxiety and weight loss. Serotonin-3 (5-HT3) receptor antagonists also modulate some of the behavioral effects of alcohol and may decrease alcohol consumption.

Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets.

Many neurological diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), are now recognized to share atypical inflammatory reactions as a major pathological feature. Neuroinflammation can both be a cause, and a consequence, of chronic oxidative stress. Cytokine-stimulated microglia generate copious amounts of reactive oxygen and reactive nitrogen species, creating a stress upon ambient neurons.

Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic lateral sclerosis.

Recent data indicate that certain pro-inflammatory cytokines are transcriptionally upregulated in the spinal cords of G93A-SOD1 mice, a model of amyotrophic lateral sclerosis (ALS). We previously showed that the receptor for tumor necrosis factor alpha (TNF-R1) was notably elevated at late presymptomatic as well as symptomatic phases of disease (J. Neurochem.

Micro1-opioid antagonist naloxonazine alters ethanol discrimination and consumption.

The endogenous opioid system is implicated in excessive ethanol-drinking behavior. However, the role of individual opioid receptor subtypes in the mechanism underlying excessive ethanol-drinking behavior is not yet well understood. Therefore, we investigated the ability of a selective micro1-opioid antagonist, naloxonazine, to modulate ethanol-drinking behavior and ethanol discrimination in a rat model with the use of ethanol self-administration and drug discrimination paradigms.