It looks like you're using an Ad Blocker.
Please white-list or disable AboveTopSecret.com in your ad-blocking tool.
Some features of ATS will be disabled while you continue to use an ad-blocker.
everytime i turn round either you or your pal are rubbishing, bad mouthing or trying to derail valid threads. you sir are undeniably a shill and a troll
Originally posted by dwmjr1985
Big Pharma is making too much money off of people having cancer.
Objective: To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
Background: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS.
Methods: The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety.
Results: During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms.
Conclusion: DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.
Trichloroacetate (TCA) and dichloroacetate (DCA) have been shown to be hepatocarcinogenic in mice when administered in drinking water. However, DCA produces pathological effects in the liver that are much more severe than those observed following TCA treatment in both rats and mice. To identify potential mechanisms involved in the liver pathology, the biotransformation of TCA and DCA was investigated in male Fischer 344 rats and B6C3F1 mice. Rodents were administered 5, 20, or 100 mg/kg [14C]TCA or [14C]DCA as a single oral dose in water. Elimination was examined by counting radioactivity in urine, feces, exhaled air, and carcass. Blood concentration over time curves were constructed for both TCA and DCA at the 20 and 100 mg/kg doses. Analysis of the data reveals two significant differences in the systemic clearance of TCA relative to DCA. First, DCA was much more extensively metabolized than TCA. More than 50% of any single dose of TCA was excreted unchanged in the urine of both rats and mice. In contrast, less than 2% of any dose of DCA was recovered in the urine as the parent compound. Second, while the blood concentration over time curves for TCA were similar in rats and mice, the blood concentrations of DCA were markedly greater in rats compared to those in mice, both when DCA was administered and when DCA resulted from metabolism of TCA. DCA was detected in the urine of TCA-treated animals and chloroacetate was found in the urine of DCA-treated animals. These metabolic products would be expected to arise from a free radical-generating, reductive dechlorination pathway. To evaluate the ability of acute doses of TCA and DCA to elicit a lipoperoxidative response, additional groups of mice were administered 0, 100, 300, 1000, and 2000 mg/kg TCA or DCA and thiobarbituric acid-reactive substances (TBARS) measured in liver homogenates. Both TCA and DCA enhanced the formation of TBARS in a dose-dependent manner, thereby providing further evidence of a reductive metabolic pathway. DCA was found to be the more potent of the chlorinated acetates in increasing TBARS formation in the livers of both rats and mice. In view of these data, it appears that the more extensive metabolism and rapid rate of elimination of DCA relative to TCA and the more potent lipoperoxidative activity of DCA may be important factors in the pathological effects associated with DCA treatment.