The payer and the piper--a view on evidence-based medicine.
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In vitro and in vivo modulation of drug metabolizing enzymes by piperine was investigated in microsomes of rats and guinea pigs. In vitro piperine caused concentration related inhibition (50% at 100 microM) of arylhydrocarbon hydroxylase (AHH) and 7-ethoxycourmarin deethylase (7ECDE) activities, which were comparable in control and 3-methylcholanthrene (3MC) treated rats. In guinea pig microsomes however, piperine caused strong inhibition at lower concentrations (35% at 10 microM) and relatively much lesser inhibition with further increase in piperine concentrations. A Dixon plot of the kinetic data of both AHH and 7ECDE indicated noncompetitive inhibition with a Ki of approx. 100 microM. In vivo, piperine given at a dose of 25 mg/kg body wt to rats caused a maximal inhibition at 1 hr of both the enzymes, while only AHH returned to normal value within 4 hr. Similarly, upon daily treatment of piperine (15 mg/kg body wt) to rats for 7 days, 7ECDE was consistently inhibited, while AHH showed faster recovery. Piperine thus appeared to cause differential inhibition of two forms of cytochrome P450 and thus would accordingly affect the steady-state level of those drugs metabolized by these pulmonary forms of cytochromes P450.
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A previously unreported involvement of the temporomandibular joint in a patient with a confirmed diagnosis of synovial osteochondromatosis is described. While etiology is not addressed, suggestive explanations for the clinical symptoms and possible recurrence prevention have been expanded upon. Despite confirming evidence, the author feels that this process may have both an urban and rural manifestation. However at present, the only references have appeared in the ancient literature of Aesop and Grimm.
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The central nervous activity of the aqueous extract of kava was examined in mice, and compared to the effect of the lipid-soluble extract. The aqueous extract caused a loss of spontaneous activity without loss of muscle tone. No hypnotic effect was seen, but some analgesia was produced. The anticonvulsant effect against strychnine was very slight and there was no evidence of local anesthetic action. There was a slight anti-apomorphine effect and tetrabenazine-induced ptosis was decreased. The lipid-soluble extract (kava resin) also decreased spontaneous motility, together with a marked reduction of motor control. Hypnosis, determined by loss of righting reflex, was produced, analgesia was marked, and a local anesthetic action evident. Kava resin also decreased apomorphine-induced hyperreactivity and partially reversed tetrabenazine-induced ptosis. Kava resin produces a greater range of pharmacological actions than the aqueous extract, and the latter is orally inactive in mice and rats. The pharmacological effects of kava ingestion appear to be due to the activity of the compounds present in the lipid-soluble fraction.
Chronic administration (sc) of the extract of the stalk of P. betle at 30 mg/kg body weight daily for 21 days produced significant decrease in oestrogen and androgen dependent target organ weights along with increase in cholesterol in adrenal, ovary and testis. Acid and alkaline phosphatase activities in serum, liver and kidney did not exhibit any toxic effect. There was marked change in morphology of testis and ovary. Vaginal smear showed prolonged dioestrus in treated female. The treated male showed decreased number and motility of sperm. Both male and female remained infertile after treatment suggesting antifertility activity of the extract on both sexes of albino rats.
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