Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trimethylphosphate, the simplest tri-alkyl ester of phosphoric acid, produces marked antifertility effects in experimental male rodents (Jackson and Jones, 1968). The predominant effect is the "functional" sterilizing action involving spermatids from which intact motile but incompetent sperm continue to be produced. Relatively high doses are required in the mouse (5 X 1 gm/kg orally), whereas it is effective in the rat at 1/10 of this level. Trimethylphosphate is remarkable in that it possesses no anticholinesterase activity, is freshly soluble and stable in water, is effective orally, and has a high level of tolerance. Whereas 500 mg/kg orally render male rats sterile for the ensuing 3 weeks, 5 times this amount, although tolerable, completely disorganizes spermatogenesis without damaging tubular architecture. Such treated rats remain infertile for 20-25 weeks, apparently retaining sexual activity, though a proportion appear to be more permanently sterilized. Rats treated weekly at 5 X 100 mg/kg orally for over 1 year have remained sterile but recover fertility 3-5 weeks from terminating treatment. "Side effects" so far observed are a sedative action and, towards 1 year of treatment, hind leg paresis, although 5 times this dose rate caused progressive loss in weight. Using phosphorus-32-trimethylphosphate the sole phosphorus-containing metabolite is dimethylphosphate (Jackson and Jones, 1968), which has no antifertility activity. With carbon-14-trimethylphosphate, S-methyl cysteine was identified as a urinary metabolite, indicating that trimethylphosphate is involved, at least in its detoxification process, as an alkylating agent. The antifertility action of trimethylphosphate is probably related to methyl alkylation. This would bring it into line with the methyl ester of methanesulphonic acid which also produces the "functional" type of sterility in rats and mice (Jackson, 1964). Like methyl methanesulphonate (Partington and Bateman, 1964), trimethylphosphate in substerilizing doses induces so-called dominant lethal mutations. Preliminary structure/activity studies have shown that tri-n-propyl- and tri-iso-propylphosphates do not affect the fertility of male mice (5 X 1 gm/kg orally). Both these esters together with tri-n-propyl- and tri-n-butyl-phosphates still have the capacity to alkylate, and like trimethylphosphate, the only metabolites in the rat were the di-alkylphosphates and corresponding S-alkyl cysteines. Whereas all these substances interact with cysteine in vitro, only trimethylphosphate reacts readily with glutathione. This might be pertinent to its biological activity.
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PMID:Chemosterilant action of trimethylphosphate in rodents. 1233 93

Hypophosphatemia (HP) with or without intracellular depletion of inorganic phosphate (Pi) and adenosine triphosphate has been associated with central and peripheral nervous system complications and can be observed in various diseases and conditions related to respiratory alkalosis, alcoholism (alcohol withdrawal), diabetic ketoacidosis, malnutrition, obesity, and parenteral and enteral nutrition. In addition, HP may explain serious muscular, neurological, and haematological disorders and may cause peripheral neuropathy with paresthesias and metabolic encephalopathy, resulting in confusion and seizures. The neuropathy may be improved quickly after proper phosphate replacement. Phosphate depletion has been corrected using potassium-phosphate infusion, a treatment that can restore consciousness. In severe ataxia and tetra paresis, complete recovery can occur after adequate replacement of phosphate. Patients with multiple risk factors, often with a chronic disease and severe HP that contribute to phosphate depletion, are at risk for neurologic alterations. To predict both risk and optimal phosphate replenishment requires assessing the nutritional status and risk for re-feeding hypophosphatemia. The strategy for correcting HP depends on the severity of the underlying disease and the goal for re-establishing a phosphate balance to limit the consequences of phosphate depletion.
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PMID:Using phosphate supplementation to reverse hypophosphatemia and phosphate depletion in neurological disease and disturbance. 2590 52