Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newborn Holstein bull calves were fed either analytical pentachlorophenol (aPCP) or technical pentachlorophenol (tPCP) for 6 wk to establish and compare the clinical and pathologic manifestations of toxicity. Four groups of three calves/group were each fed either 1 or 10 mg X (kg body weight)-1 X d-1 of either aPCP or tPCP. A fifth group served as control. Dosages of both PCP preparations were normalized to contain equal concentrations of PCP. Toxic effects were observed only at the 10 mg/kg dose in the tPCP-treated calves. These effects included decreased body weight gain, anorexia, decreased serum protein concentration, elevated serum gamma glutamyl transferase, and decreased triiodothyronine (T3) and thyroxine (T4) concentrations. Histologic lesions included cortical atrophy in the thymus and squamous metaplasia and hyperkeratous changes in the Meibomian gland of the eyelid. Thyroid function, which was assessed in vivo by measuring the rate of T3 and T4 production over 4 h after thyrotropin-releasing hormone (TRH)-challenge, was not impaired suggesting an extrathyroidal site of toxic action. Although serum chemistry indicators were suggestive of hepatic injury there were no discernable lesions. Organ weight analyses were inconclusive but there was a tendency toward enlargement of liver, kidneys and thyroid and decreased weight of lungs, spleen and thymus. A toxic effect clearly related to PCP and not its contaminants was depressed active transport of p-aminohippurate measured in kidney slices in vitro. Steady state concentrations of PCP in serum were about 40 and 90 ppm for the 1 and 10 mg/kg groups, respectively. Concentrations of PCP among the major organs were comparable.
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PMID:Assessment of pentachlorophenol toxicity in newborn calves: clinicopathology and tissue residues. 393 33

These studies determined how high-affinity monoclonal antiphencyclidine (PCP) antigen binding fragments of immunoglobulin G (Fab) affects PCP tissue concentrations and serum protein binding in male rats. Animals received an i.v. bolus dose of 1.0 mg/kg of PCP, followed at 2 hr when distribution was complete (but about 70% of the dose remained) by either saline (for controls) or an equimolar dose of anti-PCP Fab. This dose of PCP was chosen because it produces behavioral effects and ataxia for about 40 min. The rats were sacrificed over the next 16 hr (n = 3 per time point) and blood, brain, fat, heart, kidney, liver, lung, muscle and testis were collected. After anti-PCP Fab treatment, serum PCP concentrations increased significantly (P < .05) for the duration of the experiment. This resulted in a decrease in the PCP volume of distribution and systemic clearance to 11 and 12% of controls, respectively. Because these parameters decreased to a similar degree, the terminal elimination half-life was unaltered after Fab treatment. The percentage of unbound PCP in serum averaged 47 +/- 15% (mean +/- S.D.) in controls and 3 +/- 2% in Fab-treated animals for the duration of sampling. The area under the tissue concentration vs. time curves after anti-PCP Fab administration were decreased substantially in the brain (23% of controls), fat (24%), heart (52%), lung (74%) and testis (12%), but increased in the liver (137%). Because of anti-PCP Fab renal elimination, kidney PCP concentrations were significantly increased at all time points after Fab treatment (P < .05), which resulted in an 18-fold increase in the PCP area under the curve. These studies show anti-PCP Fab can rapidly remove PCP from the brain and maintain it in a highly bound form for a significant time.
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PMID:Antiphencyclidine monoclonal antibody therapy significantly changes phencyclidine concentrations in brain and other tissues in rats. 876 23