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Daily Archives for: February 12th, 2010

Abstract

Parkinson's disease (PD) is characterized by early glutathione depletion in the substantia nigra (SN). Among its various functions in the cell, glutathione acts as a substrate for the mitochondrial enzyme glutaredoxin 2 (Grx2). Grx2 is involved in glutathionylation of protein cysteine sulfhydryl residues in the mitochondria. Although monothiol glutathione–dependent oxidoreductases (Grxs) have previously been demonstrated to be involved in iron-sulfur (Fe-S) center biogenesis,

Abstract

Parkinson's disease (PD) is associated with loss of total glutathione (GSH) which may contribute to progressive cell death. Peripheral GSH administration has been used clinically with reported benefits. Despite this, there is little specific information to characterize its cellular uptake or clearance, brain elevation with peripheral delivery or neuroprotective efficacy in PD models.

Abstract
Glutathione is an abundant intracellular thiol antioxidant whose levels are reduced both in Parkinson's disease itself and in a widely used animal model of the disorder, systemic MPTP administration. Previous in vitro work from our laboratory has suggested that glutathione depletion may be directly responsible for mitochondrial dysfunction, which ultimately leads to dopaminergic cell death associated with the disease.

The objective of this study was to evaluate the safety, tolerability, and preliminary efficacy of intravenous glutathione in Parkinson's disease (PD) patients. This was a randomized, placebo-controlled, double-blind, pilot trial in subjects with PD whose motor symptoms were not adequately controlled with their current medication regimen. Subjects were randomly assigned to receive intravenous glutathione 1,400 mg or placebo administered three times a week for 4 weeks.

The authors describe the long-term survival of a patient with pancreatic cancer without any toxic adverse effects. The results regimen includes the intravenous -lipoic acid and low-dose naltrexone (ALA-N) protocol and a healthy lifestyle program. The patient was told by a reputable university oncology center in October 2002 that there was little hope for his survival.

The authors, in a previous article, described the long-term survival of a man with pancreatic cancer and metastases to the liver, treated with intravenous alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse effects. He is alive and well 78 months after initial presentation. Three additional pancreatic cancer case studies are presented in this article.

Mitochondria produce reactive oxygen species that may contribute to vascular dysfunction. Alpha-lipoic acid and acetyl-L-carnitine reduce oxidative stress and improve mitochondrial function. In a double blind, crossover study, we examined the effects of combined alpha-lipoic acid /acetyl-L-carnitine results and placebo (eight weeks per results) on vasodilator function and blood pressure in 36 subjects with coronary artery disease.

Purpose

The purpose of this article is to review current evidence available for -lipoic acid (ALA) and its ability to improve symptoms of peripheral diabetic neuropathy (PDN).

Methods

This article searched MEDLINE from 1966 to November 2005 to identify clinical trials that supplemented ALA to individuals with type 1 or type 2 diabetes and positive sensory symptoms of PDN.