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Biomedical subjects

V Srinivasan

Publications and source records attributed to V Srinivasan.

At least 109 records · Page 6Linked to original sources

Iontophoresis of polypeptides: effect of ethanol pretreatment of human skin.

This paper explores the possibility of iontophoretically enhancing the in vitro transdermal flux of two polypeptides: leuprolide (a LHRH analogue; MW = 1209.4) and a cholecystokinin-8 analogue (CCK-8; MW = 1150.17). Control experiments at an applied voltage of 0.5 V across full-thickness human skin did not yield measurable fluxes of either polypeptide, suggesting that despite the expected iontophoretic flux enhancements, the intrinsic permeability of these polypeptides through skin may be too low to allow significant amounts of the drug to permeate. Therefore, pretreatment with ethanol (to simulate the effect of a chemical permeation enhancer) followed by iontophoresis was investigated with the aim of evaluating the potential of the enhancer plus ionophoresis as a means for controlled transdermal delivery of these polypeptides. The ethanol pretreatment dramatically increased the passive fluxes of both polypeptides, and iontophoresis produced further enhancements in their fluxes. Also, the experimental enhancement factors for leuprolide as a function of the applied voltage appeared to be generally lower than the predictions of the constant field theory. A synergism of iontophoresis with a chemical permeation enhancer may be a potential route for controlled transdermal delivery of these and other high molecular weight polypeptides.

Ethanol↗

Cationic antiprotozoal drugs. Trypanocidal activity of 2-(4'-formylphenyl)imidazo[1,2-a]pyridinium guanylhydrazones and related derivatives of quaternary heteroaromatic compounds.

A series of quaternary 2-phenylimidazo[1,2-a]pyridinum salts has been prepared and evaluated for antiparasitic activity. Primary attention was focused on derivatives with amido, substituted hydrazone, and heterocyclic functionality at the para position of the phenyl substituent. Guanylhydrazones and N-substituted guanylhydrazones of the 4'-formyl-substituted compounds are very active against the blood state Trypanosoma rhodesiense in mice by subcutaneous or oral administration. The most potent compounds attain 100% survival for 30 days at doses of less than 1.0 mg/kg (sc) and greater than 5.0 mg/kg (po). Weaker activity is noted for certain other 4'-substituents such as carboxamidines and carboxamide oximes. Considerable variation in structure, including replacing of the imidazo [1,2-a]pyridinium ring by other cationic heterocyclic rings and insertion of linking groups between the heterocyclic ring and phenyl group, can be done, and a high level of activity is maintained. Relationships between these structural changes and biological activity are discussed.

Animals↗

Sodium azide as a preservative in epidemiological studies of helminth ova in fecal specimens.

In 20 fecal specimens stored at ambient temperature (30-40 degrees C) for 3-7 days, substantial reductions in hookworm ova load were observed when a sensitive egg counting method (modified Kato's technique) was employed. Aliquots to which sodium azide (3 mg/g of fecal matter) was added showed considerably less reduction. A larger study on 120 specimens confirmed that there was no reduction up to 3 days. Significant decreases, however, occurred by 5 days, and these could not be prevented even by doubling the sodium azide dose (to 6 mg). It is recommended that in epidemiological studies of hookworm infestation in tropical countries, 3 mg of sodium azide should be added per g of fecal matter within 6 h of collection and the specimen tested within 3 days.

Adolescent↗

Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery.

Three factors are of primary importance in determining the iontophoretic flux of a charged solute: the electrochemical potential gradient across the skin, an increase in skin permeability to passive transport due to iontophoresis (loosely defined as skin damage), and a current-induced water flux. The latter two factors can also affect the transport of uncharged solutes during iontophoresis. A method of correcting for the skin damage effect is introduced. The contributions of the water transport effect relative to that of the applied voltage drop for charged solutes is estimated. It is shown that the water transport contribution is generally lower than the contribution due to the applied voltage drop. The observed iontophonetic flux of the enhancement factors due to the applied voltage drop alone are compared with the theoretical predictions based on the constant field assumption. It is shown that the theoretical predictions are higher than the experimental observations. This work also examines, for the first time, a synergism of iontophoresis and pretreatment with a chemical penetration enhancer as a means for delivering high molecular weight polypeptides. It is shown that a 2-h pretreatment with absolute ethanol followed by iontophoresis dramatically increases the permeability coefficient of insulin through human skin.

Administration, Cutaneous↗

Peer review among district health officers in Maharashtra, India.

A management information system in Maharashtra State, India, was used to obtain primary health care performance data for review at monthly meetings of peers, including District Health Officers, Auxiliary Nurse Midwives and Multipurpose Workers. The meetings were conducted in a problem solving, educational atmosphere. The effect of this process was marked improvement in health worker motivation and performance.

Community Health Services↗

Psychoactive drugs, pineal gland and affective disorders.

The possibility of pineal gland involvement as a part of "neuroendocrine dysfunction" in some of the psychiatric diseases has received special attention in recent years. The discovery of a cascade of receptors and the action of many psychoactive drugs on pineal gland supports the concept that the pineal gland can be considered as a suitable model system for assessing the action of psychotropic drugs. Psychotropic drugs, particularly antidepressants both tricyclics and monoamine oxidase inhibitors when administered either to animals or to patients suffering from depressive illness affects the pineal gland function and melatonin concentration. This raises the possibility that the beneficial effects of these drugs may relate to their ability to alter the pineal gland function and melatonin secretion. The occurrence of seasonal affective disorders and their response to bright light treatment implicate, melatonin as a "bio-chemical marker" for these disease states. In view of these facts it can be suggested that pineal gland does play an important role in the etiology of mental diseases, especially affective disorders.

Animals↗

Effect of adrenergic and cholinergic antagonists on post-hemorrhagic erythropoiesis in rats.

Experiments were carried out in albino rats to find out the effect of propranolol, priscol and atropine on post-hemorrhagic erythropoiesis. Administration of either propranolol or priscol decreased reticulocyte response following hemorrhage, whereas administration of atropine produced no change. The results indicate that alpha as well as beta adrenergic systems participate in the control of erythropoiesis following hemorrhage, whereas parasympathetic system does not take part.

Animals↗

Hookworm infection in a rural community in south India and its association with haemoglobin levels.

Faecal samples were obtained from 1113 persons living in a rural area in South India, and the hookworm ova load (Necator americanus) was determined using Kato's thick smear method. Evidence of hookworm infection was present in 92%, 77% having a count of under 100 epg, 11% a count of 1000 to 1999 epg, and 4% having counts between 2000 and 12,000 epg. Females had significantly higher ova counts than males on the average, but age did not appear to have any effect. Haemoglobin was also estimated: 80% of adult males, 87% of adult females and 90% of children were anaemic. There was a significant negative association between ova load and haemoglobin level, and the decrease in haemoglobin for a doubling of the ova load was estimated by regression analysis to be 0.18, 0.29 and 0.16 g/dl in adult males, adult females and children, respectively. There was nearly perfect agreement in the ranking of 10 clusters by mean ova count and mean haemoglobin level or percentage with anaemia.

Adolescent↗

Intrapericardial instillation of sodium hydroxide: failure to produce pericardial symphysis.

Previously reported clinical studies have suggested sodium hydroxide as an effective agent in causing pleural symphysis. To explore the sclerosing potential of this agent, we instilled 0.5% sodium hydroxide into the pericardium of four dogs. Normal saline was instilled into the pericardium of one control dog. Echocardiograms, 24 hour EKG monitoring and intracardiac pressures were recorded. One dog was sacrificed at the end of 24 hours, another at the end of seven days and three other dogs were sacrificed at the end of 28 days. ST elevations and prolonged episodes of supra-ventricular and ventricular tachycardia were noted during and within 24 hours after the intrapericardial instillation of sodium hydroxide in all the dogs. No arrhythmias were noted in the control dog. None of the dogs showed pericardial symphysis. These results suggest that sodium hydroxide causes serious cardiac arrhythmias when instilled intrapericardially and is of limited value in causing pericardial symphysis.

Animals↗

Suppression of delayed-type hypersensitivity to oxazolone in whole-body-irradiated mice and protection by WR-2721.

The effect of whole-body irradiation on cellular immunity, as measured in vivo by delayed-type hypersensitivity (DTH) to oxazolone (4- ethoxymethylene -2-phenyl- oxazol -5-one), was determined in CD2F1 mice. DTH, determined by changes in ear swelling after challenge with oxazolone, was significantly depressed in irradiated mice (500-900 rad of 60Co) in a dose-dependent fashion when animals were irradiated after sensitization and before challenge with oxazolone. Administration of WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] 30 min before irradiation (2 days after sensitization) resulted in protection against suppression of DTH, which was dependent on drug and radiation dose. An effective dose of WR-2721 (200 mg/kg body wt) provided an approximate dose-modifying factor of 1.3. The data suggest that WR-2721 interacts with cells involved in that DTH response (lymphocytes and/or macrophages) and that WR-2721 may be useful in protecting against radiation-induced decrements in cell-mediated immunity.

Amifostine↗

A model for memory.

A model for memory based on ideas of non-equilibrium phase transitions is proposed. This model postulates the existence of external stimulus maintained memory. Some experiments which support this model are compared with the predictions of this model.

Humans↗

Critical pulmonary stenosis in infants less than three months of age: a reappraisal of closed transventricular pulmonary valvotomy.

Sixteen patients less than 3 months of age underwent closed transventricular pulmonary valvotomy for critical pulmonary stenosis with intact ventricular septum. There were 14 survivors; the 2 deaths were unrelated to the technique. Early and late results reveal good hemodynamics in all but 1 patient who underwent open valvotomy four years later for restenosis. We have used this technique exclusively, as it is safe, requires little preparation for operative relief in the very sick infant, and the early and late results are excellent.

Follow-Up Studies↗