Evaluation of antimuscarinic activity in human volunteers: a teaching aid in clinical pharmacology.

The antimuscarinic activity of oxyphenonium bromide, diphenhydramine hydrochloride and astemizole were evaluated in six volunteers. The parameters used were salivary secretion, heart rate and pupillary size. The results indicated that the changes in heart rate and pupillary size and measurements were not convenient parameters for class room demonstration. However, salivary secretion and dryness of mouth were found to be reliable parameters for measurement. It was concluded that simple procedures like evaluation of antimuscarinic activity could be introduced as teaching aids in clinical pharmacology for undergraduate students.

Possible mechanism of endosulfan-induced enhancement of memory acquisition and retention in mice.

The effects of pre-training and post-training administration of endosulfan on retention of a step-down passive avoidance task was studied in mice. Endosulfan at doses of 1.0 mg/kg(ip) and 2.0 mg/kg(ip) enhanced memory acquisition and retention. This effect of endosulfan was possibly mediated by interaction with cholinergic neurotransmission, as scopolamine (0.5 mg/kg, ip) significantly antagonized the memory enhancing effects of endosulfan. Clonidine (0.05 mg/kg, ip) did not have any effect on enhancement of memory produced by endosulfan, thus indicating possibly no role of noradrenergic system.

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.

Effect of subacute insecticide exposure on body weight, drug responses & electrical convulsions in mice.

Effect of subacute insecticide exposure was studied in male albino mice treated with phosphamidon, propoxur or aldrin at 1/40 LD50 dose intraperitoneally daily for 8 wk. The parameters studies included body weight, pentobarbitone (50 mg/kg) sleeping time, chlorpromazine (6 mg/kg) induced motor incoordination and convulsions induced by leptazol (100 mg/kg) and electrical stimulation (18 mA for 0.2 msec). While body weight and electrically induced convulsions were not affected, the effect of various drugs was significantly decreased. The observed changes may be due to the induction of hepatic drug metabolising enzymes by the insecticides. The study suggests that certain dose adjustment of drugs may be necessary in those exposed to insecticides over long periods.

Effect of subacute DDT on pharmacokinetics of isoniazid and liver function in rabbits.

DDT administration (30 mg/kg per day, po, for 21 consecutive days) to rabbits showed an increase in peak plasma concentration and a decrease in time to reach peak plasma concentration of isoniazid whereas no change was observed in elimination rate constant and area under the plasma concentration-time curve. DDT treatment caused increased absorption of isoniazid. Early signs of hepatic damage were also observed. Since there was no change in the levels of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase, it can be concluded that DDT does not significantly affect liver function at the dosage used. The observed elevated levels of alkaline phosphatase could be due to direct activation of the enzyme. Leukopaenia and neutropaenia with relative lymphocytosis indicated that DDT might have suppressant effect on granulocyte cell line of WBCs.

Conjunctival impression cytology in children with persistent diarrhea as indicator of pre-clinical vitamin A deficiency.

Children with persistent diarrhea may be at a higher risk of developing vitamin A deficiency. Impression cytology of the conjunctiva has been shown to be a simple and objective diagnostic test for detection of early, physiologically significant vitamin A deficiency. We studied, changes in conjunctival impression cytology using millipore HAWG filter paper in 25 children aged less than 5 years suffering from persistent diarrhea, who had no ocular manifestations of vitamin A deficiency (Group I). Twenty five age matched healthy children constituted the control group (Group II). Seventeen of the 25 children with persistent diarrhea (68%), showed the following abnormalities: (i) the shape of the epithelial cells were abnormal, and (ii) goblet cells were absent. The study could be repeated after 2 weeks of administration of vitamin A in 7 children. Reappearance of PAS-positive mucous glycoproteins and presence of normal epithelial cells was demonstrated in all 7 children retested. This test can prove to be of significant value in assessment of response to vitamin A therapy. This study shows that children with persistent diarrhea appear to be at high risk for developing vitamin A deficiency, which can be detected by the technique of conjunctival impression cytology. This is a cheap and reliable method of detecting preclinical vitamin A deficiency which can be performed by a pediatrician in the office laboratory.

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.

Control of persistent vesical bleeding due to radiation cystitis by intravesical application of 15 (S) 15-methyl prostaglandin F2-alpha.

A 45 year old female who received radiotherapy for stage II-B uterine cervical cancer four and half years ago, presented with persistent hematuria due to radiation cystitis. 15 (S)-15-methyl prostaglandin F2-alpha (1 mg in 100 ml of normal saline) was instilled into the bladder daily for two days. The severity of bleeding decreased considerably. However, significant hematuria recurred 19 days later which continued despite bladder irrigation with normal saline. 1 mg of 15 (S) 15-Me PGF2 alpha mixed with hydroxyethyl cellulose gel to a volume of 10 ml was then instilled into the urinary bladder daily for three days and macroscopic hematuria ceased. Urinary frequency and urgency were the side effects which lasted for ten days. There has been no recurrence of macroscopic hematuria during the five months follow-up. In conclusion, 15 (S) 15-Me PGF2-alpha may be administered intravesically to control moderate hematuria due to radiation cystitis.