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Biomedical subjects

P L Sharma

Publications and source records attributed to P L Sharma.

At least 55 records · Page 3Linked to original sources

Effect of fatty diet on pharmacokinetics and pharmacodynamics of a liquid theophylline preparation in volunteers.

The effect of a standard breakfast and a fatty breakfast on the pharmacokinetics and pharmacodynamics of a theophylline liquid preparation (160 mg-single dose) was examined in 6 healthy, non-smoking male volunteers. The plasma theophylline concentrations after both standard and fatty diet were found to be comparable at each point of time and pharmacokinetic parameters like Cmax, Tmax, T1/2a, T1/2 beta and AUC0-alpha, were also comparable. However, the time taken to attain the therapeutic plasma concentration was earlier and sustained along with the standard breakfast in comparison to that with fatty breakfast. Peak change in PEFR and pulse rate was also observed earlier with the standard diet than with fatty diet. The plasma theophylline concentrations produced after both diets were insufficient to produce any detectable change in subjective symptoms like tremor palpitation, heart burn, nausea, restlessness and tenseness. However, theophylline after fatty breakfast was better tolerated than that after a standard breakfast.

Adult↗

Patients' attitude towards health care at a teaching hospital in India.

Using a questionnaire, 362 patients attending the outpatients services of Internal Medicine of Nehru Hospital attached to our institution were randomly interviewed. Seventy per cent of the patients were in the 21-50 years age range; 50% came from rural and 50% from urban areas. Forty per cent travelled more than 30 Km; 72% used a public transport to reach hospital. Most patients had an income less than Rs. 1000/-. Ninety per cent had already consulted another medical practitioner earlier. The largest number of complaints related to the gastrointestinal, cardiovascular and respiratory systems. On an average 1-2 drugs were prescribed per patient; only 13% of these were available at the hospital dispensary. Most patients were willing to purchase the prescribed drugs from the market.

Adult↗

Antimicrobial drug use in urology.

Antimicrobial drug utilization patterns were studied on patients in the Urology Ward of Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh. The study was done over a six-month period in which antimicrobial prescription for all patients admitted under urology services were monitored and followed. There were 57 cases of benign hypertrophy of the prostate, 40 of urinary calculi and 20 each of congenital malformation, malignancies, strictures and other conditions. Gentamycin and cotrimoxazole were the most frequently used antimicrobials, as calculated by the DDD/100 bed days.

Adult↗

Determination of the optimal analgesia-potentiating dose of caffeine and a study of its effect on the pharmacokinetics of aspirin in mice.

The addition of caffeine 10 mg/kg to analgin, paracetamol and aspirin increased the potency of the combination compared to that of the analgesic used alone, giving a potency ratio of 1.58, 2.5 and 3.23, respectively as assayed by the writhing method in mice. Increasing the dose of caffeine further reduced the potency of the combination so that with 100 mg/kg caffeine the potency ratio for the combination against the analgesic alone was analgin 1.25, paracetamol 0.94 and aspirin 0.88. The Cmax, Tmax, t1/2 and AUC of plasma salicylate was not significantly different when aspirin 65 mg/kg was given alone or in combination with caffeine 10 mg/kg p.o. in mice. Therefore, caffeine is maximally effective in potentiating the effect of analgesics at a dose of 10 mg/kg and this potentiation is not due to a pharmacokinetic interaction with the analgesic, and also not due to phosphodiesterase (PDE) inhibition.

Acetaminophen↗

Topical corticosteroids usage in dermatology.

Prescribing of topical corticosteroids was studied in 200 patients attending the dermatology outpatients, randomly auditing the written prescriptions. Data with regard to potency, quantity, frequency, duration and site of application was collected and analyzed. Potent topical steroids were commonly used in 86 (43%) patients. The quantity of topical steroid was mentioned in only 4% patients whereas the frequency was specified in 77%, the site in 69% and the duration in 55% patients, respectively. The importance of these parameters is discussed, guidelines regarding use of topical steroids suggested.

Administration, Topical↗

Possible mechanism of haloperidol-induced enhancement of memory retrieval.

The effects of pretest administration of haloperidol on retention of a step-through passive avoidance task was studied with a 3-day training and retention test interval. Haloperidol at doses of 0.3 mg/kg and 0.5 mg/kg i.p. enhanced memory retrieval. This effect of haloperidol is possibly mediated by interaction with alpha 2-adrenergic receptors, that results in increasing the noradrenergic transmission, or it could be due to direct interaction with dopamine receptors. Yohimbine (2.5 mg/kg) also enhanced memory retrieval, as shown by haloperidol. Clonidine (0.05 mg/kg) significantly antagonized the effect of haloperidol on memory retrieval. Scopolamine (0.5 mg/kg) did not have any effect on enhancement of memory produced by haloperidol.

Animals↗

Murine models for evaluating antiretroviral therapy.

The pandemic of the acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus type 1 (HIV-1), requires rapid development of effective therapy and prevention. Analysis of candidate anti-HIV-1 drugs in animals is problematic since no ideal animal model for HIV-1 infection and disease exists. For many reasons, including small size, availability of inbred strains, immunological reagents, and lymphokines, murine systems have been used for in vivo analysis of antiretroviral agents. Here we review currently available murine models involving HIV-1 in transgenic mice and in chimeric mice reconstituted with human cells, as well as murine systems using retroviruses of the subfamily Oncovirinae rather than Lentivirinae. We report our results on various antiretroviral treatment strategies, including chemoprophylaxis after acute retroviral exposure, therapy of chronic viremia, quantitative analysis of combination therapy, and therapy during pregnancy and in the neonatal period aimed at preventing viremia in the offspring. Due to our highly effective postexposure treatment protocols with 3'-azido-3'-deoxythymidine (zidovudine) combined with recombinant human interferon-alpha A/D, retrovirus-inoculated mice developed immunity to the virus to which they were exposed, which will allow us to determine the nature of protective antiretroviral immunity in inbred mice.

Animals↗

Simian immunodeficiency virus displays complex patterns of RNA splicing.

The human and simian immunodeficiency viruses encode at least six gene products that apparently serve regulatory functions. To evaluate the regulation of simian immunodeficiency virus gene expression at the level of RNA splicing, we used the polymerase chain reaction to amplify and clone cDNAs corresponding to a large array of mRNAs from infected cells. We identified mRNAs that used splice acceptor sites upstream of the initiator codons for tat, rev, vpr, nef, vif, and vpx, suggesting that these proteins may be expressed from different mRNAs. We also provide hybridization data suggesting that the same splice acceptor site may be used for both rev and env mRNAs. Furthermore, we isolated both tat and rev cDNAs that utilized three alternative splice acceptor sites at the start of coding exon 2, indicating that different versions of these proteins may be encoded. Finally, approximately 10 to 20% of simian immunodeficiency virus mRNAs spliced an intron from their untranslated 5' ends, and sequences contained within this intron constituted a portion of the tat-responsive TAR element. Thus, alternative pre-mRNA splicing adds a level of complexity to simian immunodeficiency virus expression, which may affect several levels of gene regulation.

Animals↗

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.

Animals↗

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.

Animals↗

Controlled clinical trial of propranolol alone and in combination with dilazep in patients with angina pectoris.

The present study was performed to see if the combined treatment with propranolol and dilazep offers any advantage over monotherapy with propranolol alone in angina of effort. Thirty-four patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both propranolol alone (20-80 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in anginal attacks, consumption of nitroglycerin tablets and increased exercise tolerance. Propranolol in combination with dilazep produced more reduction in these parameters as compared to when it was given alone. However, this difference was not significant. The combination of the two drugs produced a significant reduction in supine systolic blood pressure and in rate-pressure product. Laboratory data did not reveal any dysfunction of liver, kidneys and hemopoietic system. The results obtained support the anticipated additional benefit from combined therapy with propranolol and dilazep in terms of some increase in efficacy.

Angina Pectoris↗

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.

Animals↗

Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance responses in rats.

The effects of subcutaneous administration of morphine, buprenorphine, pentazocine and nalorphine were studied at two dose levels in rats (low dose x 10 and high dose x 20 of equivalent human dose) on the performance of active avoidance responses using a shuttle box. Pretraining injections of both doses of pentazocine and low dose nalorphine impaired acquisition on day 1 and day 2. Morphine and buprenorphine (at both dose levels) and high dose nalorphine did not affect the acquisition process. Post-training administration of morphine (high dose) and buprenorphine (both doses) delayed extinction of active avoidance responses. Low dose of morphine, high dose of pentazocine and both doses of nalorphine did not appreciably affect the extinction process. Mu opioid receptor agonists probably act as reinforcers to facilitate memory.

Animals↗

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers.

The pharmacokinetic and pharmacodynamic studies of four different brands of propranolol (Inderal, Ciplar, Corbeta and Propal) were carried out after single and multiple dosing on six normal adult healthy volunteers in a randomized crossover fashion to determine any inter-brand variations in bioavailability and pharmacodynamic effects. No significant difference was observed in any of the pharmacokinetic and pharmacodynamic parameters of four different brands of propranolol studied.

Adult↗

Genetic and molecular characterization of an epidemic plasmid coding for multidrug resistance in Salmonella typhimurium of human origin.

All 201 multidrug resistant Salmonella typhimurium strains isolated from epidemics in India contained nonconjugative (157 strains) or conjugative (44 strains) Inc F1me multiresistance plasmids. Two small R-plasmids of 7 MDa which coded for resistance to either ampicillin or streptomycin and sulfamethoxazole were also detected along with other plasmids. The small plasmids were members of group 1 and group 2 incompatibility groups. Restriction endonuclease analysis of conjugative (96 MDa) and nonconjugative (88 MDa) Inc F1me plasmids showed considerable similarity except for the presence of unique fragments among both the groups and the loss of fragments corresponding to the smaller size of the nonconjugative plasmid. A single Inc F1me plasmid appears responsible for various outbreaks of multiresistant S. typhimurium in different parts of India.

Conjugation, Genetic↗

Necrotizing otitis externa (a new aid to management).

We found the implantation of Gentamicin beads a simple and very inexpensive method for long-term management of malignant (necrotizing) otitis externa. It not only cuts the cost of treatment and shortens the length of stay in hospital but is equally free of potential complications associated with prolonged parenteral Gentamicin therapy.

Aged↗