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Biomedical subjects

N Das

Publications and source records attributed to N Das.

At least 73 records · Page 4Linked to original sources

Rapid spread of HIV among injecting drug users in north-eastern states of India.

Manipur, a north-eastern state of India bordering Myanmar, has experienced very rapid transmission of the human immunodeficiency virus (HIV) among its vast drug-injecting population. Seroprevalence among intravenous drug users increased from 0 per cent in September 1989 to 50 per cent within six months. With a minimum injecting population of 15,000 and seropositivity of over 50 per cent, the infection quickly spread to the population at large. One per cent of antenatal mothers tested seropositive by 1991. Forming part of the area of South-East Asia known as the Golden Triangle, and producing opium and its derivatives, Myanmar shares a long international border with four States of the region, and populations with a common language and culture move freely across borders. Two other north-eastern states of India bordering Myanmar have faced a similar epidemic within a short period of time. As a result of serosurveillance for HIV since 1986, the epidemic could be detected at an early stage. The present paper provides an account of the results of ongoing comprehensive studies conducted in the north-eastern states of India on drug-related HIV infection, already a serious problem, but possibly still restricted to that region of the country. The prevalence of intravenous drug users, their HIV serological status, the demographic profile, risk behaviour, the spread of the infection to other groups and the problems of harm minimization are also covered.

Adolescent↗

Sugar-coated liposomes: a novel delivery system for increased drug efficacy and reduced drug toxicity.

The uptake of glycoside-bearing liposomes by macrophages has been studied in vitro. Since the uptake was found to be specific for the end sugar attached to the glycoside, the possibility is raised that glycoside-bearing liposomes might be used in vivo as systems to deliver drugs to macrophages. Using the antileishmanial drug urea stibamine, these delivery systems have been tested in vivo against model leishmaniasis. The results indicate that the drug encapsulated in sugar-coated liposomes is much more potent in comparison with normal liposome-encapsulated drug or to the free drug. Mannose-grafted liposomes are more efficient in transportation of drugs compared with those bearing glucose. Toxicity studies involving blood parameters, histological staining of tissues and specific enzyme activities related to liver function, show no apparent toxicity with the drugs. Hence, drug encapsulated sugar-coated liposomes may have possible applications to humans.

Animals↗

Central modulation of croton oil induced subacute inflammation in rats.

Earlier studies from this laboratory have indicated that CNS exerts a modulatory influence over acute inflammation in rats. The present study examines the existence of a similar modulatory effect of CNS on a subacute inflammatory paradigm, the croton oil-induced granuloma pouch in rats. The inflammatory exudate, collected on 6th day after croton oil administration, was found to be substantially less in intracerebroventricular (icv) cannulated and artificial cerebrospinal fluid administered rats as compared to their uncannulated saline (ip) administered counterparts. This effect may be due to stress induced by cannulation. Centrally administered pharmacological agents which attenuate central monoaminergic, cholinergic or prostaglandin systems had insignificant effects on the inflammatory exudate. However, induced increase in central noradrenergic activity was found to attenuate the inflammation when the treatment was done before, but not 48 hr after, the induction of the inflammation. In contrast, induced increase in central serotonergic activity had no effect on the volume of the inflammatory exudate at either time period. Steady state levels of rat brain noradrenaline and serotonin, but not dopamine, were enhanced by the inflammatory procedure. However, these effects may be attributed to the stress induced by croton oil inflammation. The investigation indicates that the modulatory influence of CNS remains limited to the acute phase of inflammation, being exerted mainly by the central noradrenergic system. Once the inflammation has progressed, this modulatory influence of CNS is no longer apparent.

Animals↗

Targeting of plant glycoside-bearing liposomes to specific cellular and subcellular sites.

The possibility of using liposomes as an effective drug delivery system has been studied by incorporation of two plant glycosides of varying terminal sugar residues onto the surface of liposomes and examination of their distribution in different tissues. The two glycosides, corchorusin D and asiaticoside having glucose and rhamnose respectively at the terminal ends wee selected for the purpose. The hepatic uptake of liposomes made from egg lecithin, cholesterol and dicetyl phosphate and either of the two glycosides was compared. The hepatic uptake of asiaticoside bearing liposomes was reduced, whereas that of corchorusin D bearing liposomes was enhanced and was specific for glucose. Liver perfusion followed by cell separation showed that the uptake is mostly into the non-parenchymal cells of liver. The distribution of corchorusin D bearing liposomes was maximal in the lysosomal fraction of the non-parenchymal cells. Ways of using corchorusin D bearing liposomes as delivery systems for drugs or enzymes to lysosomes have been sought.

Agglutination Tests↗

Modulation of humoral immune responses by endogenous opioids.

The effects of opioid agonists and antagonists were investigated on humoral immune mechanisms in mice and rats. Opioid agonists like morphine, Leu-enkephalin, and Met-enkephalin, enhanced antigen-induced histamine release from mixed peritoneal cells of rats in vitro; this enhancement was effectively antagonized by naloxone, an opioid antagonist. Naloxone, per se, decreased anaphylactic mortality in doses of 10 mg/kg, while it increased mortality in a dose of 1 mg/kg. Reduced IgE antibody titer, measured by passive cutaneous anaphylaxis, decreased hemagglutination titer to sheep red blood cells, blocked histamine release from mixed peritoneal cells of rats in vitro induced by antigen, but had no significant effect when histamine release was induced by compound 48/80. Thus, it appears that endogenous opioids are involved in humoral immune responses.

Anaphylaxis↗

Intracerebroventricularly administered bradykinin augments carrageenan-induced paw oedema in rats.

Intracerebroventricular (i.c.v.) administered bradykinin (2.5 and 5.0 micrograms/rat) was found to augment carrageenan-induced acute paw oedema throughout the 4 h post-carrageenan observation period. The effect was statistically significant with the higher dose. The pro-inflammatory effect of i.c.v. bradykinin was antagonized following pretreatment with hemicholinium and atropine ethoiodide administered i.c.v., drugs that reduce central cholinergic activity. Similarly, central administration of drugs that inhibit the synthesis of eicosanoids, hydrocortisone, diclofenac and paracetamol, also attenuated the pro-inflammatory effect of bradykinin. The findings indicate that the inflammation-promoting effect of centrally administered bradykinin involves the central prostaglandin and cholinergic neurotransmitter systems.

Animals↗

Brain monoamines during carrageenan-induced acute paw inflammation in rats.

Paw inflammation was induced in rats by sub-plantar administration of carrageenan. Significant inflammatory oedema was observed 1 h later and the peak effect was noted between 3-4 h. The oedema was markedly reduced after 12-24 h. Steady state levels of whole brain and hypothalamic monoamines were estimated spectrofluorometrically during the course of the carrageenan-induced paw inflammation. In addition, the rate of accumulation of the brain 5-hydroxytryptamine (5-HT) and noradrenaline (NA) was assessed in clorgyline-pretreated rats during the inflammation. The whole brain and hypothalamic concentrations of 5-HT and NA were augmented during the early phase of the inflammation, but fell below control values when peak inflammation was achieved. Thereafter, the monoamine levels tended to normalize by 24 h when the inflammation had virtually subsided. On the contrary, whole brain and hypothalamic dopamine levels remained largely unaffected. The rate of accumulation of brain 5-HT and NA were enhanced during carrageenan inflammation, indicating that the turnover of these monoamines is augmented during the inflammatory process. The results suggest that acute peripheral inflammation may significantly affect central 5-HT and noradrenergic activity in rats.

Animals↗

Endogenous opioids and immune responses: an experimental study.

Possible involvement of endogenous opioids in humoral immune responses has been explored in the experimental animals. Opioid agonists like morphine and leu-enkephalin significantly enhanced antigen-induced histamine release from the peritoneal mast cells of sensitised rats in vitro; this was effectively antagonised by naloxone. Naloxone itself inhibited antigen-induced histamine release. Animals were effectively protected against anaphylactic shock by naloxone which also antagonised morphine-induced increase in anaphylactic mortality. Naloxone reduced haemagglutination titre to sheep red blood cells and IgE antibody titre as measured by passive cutaneous anaphylaxis. Thus, endogenous opioids appear to be involved in the mediation of humoral immune responses. They seem to act at various steps in the immune mechanism viz (i) antibody production and (ii) release of mediators of hypersensitivity reactions.

Anaphylaxis↗

Oral application of insulin encapsulated liposomes.

125Iodine labelled insulin encapsulated liposomes were introduced orally to rats. After different intervals of feeding, blood from the portal vein and heart was collected. The plasma was passed through a Sepharose 2B column to establish the presence of liposomes or intact hormone. Liposomal and hormonal fractions from the column loaded with plasma from the portal vain contained radioactivity. It was found that approx. 60% of the loaded radioactivity was associated with the liposomes whereas 20% of the loaded count was found with the hormonal fractions. It is noted that undegraded protein is not detected in portal plasma from rats fed with free insulin. When plasma from the heart of rats fed with liposomal insulin was passed through Sepharose 2B column, neither liposomes nor insulin was detected.

1,2-Dipalmitoylphosphatidylcholine↗

Plant glycosides in a liposomal drug-delivery system.

Plant glycosides were incorporated into the liposomal surface to study their sugar-specific uptake by various tissues. Two steroid glycosides, namely floribundasaponin D, with rhamnose as terminal sugar, and gracillin, with glucose and rhamnose as end sugars, were selected for the purpose. 125I-human IgG encapsulated liposomes composed of egg lecithin (phosphatidylcholine), cholesterol, dicetyl phosphate (optional) and either floribundasaponin D or gracillin, when injected into the tail vein of rat, showed significantly higher uptake in the rat liver than in appropriate controls. Whereas the uptake of floribundasaponin D liposomes was observed to be non-specific, the increased uptake of the gracillin liposomes, as judged from the inhibition studies with asppropriate sugars, was specific for glucose, although the receptor was unable to distinguish between the alpha and beta anomers ('anomerically blind'). The liver-perfusion studies showed that the uptake of gracillin liposomes was mostly by non-parenchymal cells.

Animals↗

Suppression of liver uptake of orally fed liposomes by injection (i.p.) of dextran sulfate 500.

125Iodine labelled human immunoglobulin-G encapsulated liposomes were administered orally to rats. Distribution of radioactivity was checked in various tissues and in portal blood. The effect of dextran sulfate (DS 500,000 m. wt., liver blockade agent) injection (i.p.) on the liver uptake of liposomes and on the amount of liposomes appearing in the portal blood from the gastrointestinal tract have been studied. An increased amount of radioactivity was observed in the portal blood and the amount of radioactivity in the liver decreased appreciably after injection of dextran sulfate. In both the cases the action of dextran sulfate started 2 hours after injection and reached maximum at 12 hour, falling slightly at 24 hour.

Administration, Oral↗

Inhibition of carrageenin-induced pedal oedema in rats by immobilisation stress.

The effect of immobilisation stress on acute pedal inflammation induced by carrageenin, and the mechanism of stress-induced anti-inflammatory effect, were investigated in male Wistar strain albino rats. Carrageenin-induced pedal inflammation oedema was attenuated by immobilisation stress in a time-dependent manner, when the rats were restrained for 30 min, 1 h, and 2 h immediately after the induction of the inflammation. Pentobarbitone exhibited significant anti-inflammatory effect of its own in an anaesthetic dose and also inhibited stress (1 h)-induced attenuation of the inflammation. Likewise, lignocaine, injected behind the knee joint of the inflamed limb, attenuated the inflammation and also inhibited the stress-induced anti-inflammatory effect. These findings indicate the importance of the central nervous system (CNS) and the afferent/efferent neural pathways from and to the inflammatory site, in inflammation and in stress-induced anti-inflammatory effect. Earlier studies from this laboratory have shown that the central noradrenergic, histaminergic, serotonergic and GABA-ergic neurotransmitter systems have a modulatory anti-inflammatory effect on carrageenin-induced pedal oedema. Since all these neurotransmitter systems have been reported to be activated by stress, their role was assessed in the inflammation-attenuation effect of immobilisation stress. The present studies indicate that, of these neurotransmitters, only the central noradrenergic system is involved in the anti-oedema effect of stress. Endogenous opioid peptides may also be involved in the stress-inflammation interaction, since naloxone inhibited the stress effect. Bilateral adrenalectomy and peripheral chemical sympathectomy, induced by i.p. administration of 6-hydroxydopamine, augmented carrageenin oedema and antagonised the stress-induced anti-inflammatory effect. However, metyrapone, an inhibitor of endogenous corticoid synthesis, failed to inhibit the stress effect. These findings indicate that the sympatho-medullary system, which is known to be activated during stress, is responsible for the observed anti-inflammatory effect of immobilisation stress, rather than augmented release of adrenal corticoids. It is suggested that the observed inflammation reducing effect of immobilisation stress is a consequence of increased central noradrenergic and peripheral sympatho-medullary activity.

5,6-Dihydroxytryptamine↗

Effect of pre-existing inflammation on carrageenan-induced paw oedema in rats.

Twenty-four hours after injection of carrageenan into one hind paw, injection of the same amount into the contralateral paw produced a significantly attenuated inflammatory response. However, when the second injection was given 7 days later, the inflammation induced in the contralateral paw was comparable with the initial response to carrageenan. A time-course study of carrageenan-induced inflammation in rats showed that significant oedema persisted 24 h after carrageenan administration and complete recovery was achieved in 7 days. The attenuated inflammatory response in the contralateral paw after 24 h was antagonized by bilateral adrenalectomy and chemical sympathectomy induced by 6-hydroxydopamine. Carrageenan-induced paw oedema was also significantly less in rats with subacute inflammation induced by the croton oil granuloma pouch technique. This attenuated response was antagonized by pretreatment of the rats with metyrapone, an inhibitor of adrenocorticoid synthesis, and by 6-hydroxydopamine. It is likely that the pre-existing acute or subacute inflammation attenuates the inflammatory response of carrageenan, by acting as a stressor, inducing activation of the sympatho-adrenal system.

Adrenalectomy↗

Central catecholaminergic modulation of carrageenin-induced pedal oedema in rats.

Intracerebroventricularly (i.c.v.) administered noradrenaline (NA) and L-dopa, but not dopamine (DA), attenuated carrageenin-induced pedal oedema in rats. Centrally administered reserpine and the catecholaminergic neurotoxin, 6-hydroxydopamine (6-HD), augmented the inflammatory oedema. Pharmacological treatments, which selectively increase central DA, induce DA neurone degeneration and affect DA receptor activity, were singularly ineffective in modifying the inflammatory response of carrageenin. Centrally administered phentolamine, an alpha-adrenergic receptor antagonist, produced a dose-related dual effect on the peripheral oedema. Lower doses of phentolamine produced a paradoxical NA-like oedema-attenuating effect, which was not evident in 6-HD-treated rats; however, a larger dose of the drug had no per se effect but antagonised the oedema-inhibiting effect of centrally administered NA. Propranolol, a beta-adrenergic receptor antagonist produced inconsistent effects, with a lower and higher dose of the drug showing no effect, while a median dose induced an inhibitory effect on the peripheral oedema. Bilateral adrenalectomy failed to antagonise the anti-inflammatory effect of central NA, but peripheral degeneration of sympathetic neurones, induced by i.p. administered 6-HD, inhibited the effect of NA. The results of the study indicate that central NA, but not DA, exerts a modulatory inhibitory effect on peripheral oedema induced by carrageenin. This effect of central NA appears to be dependent upon the peripheral sympathetic system and not on the activation of the adrenal corticoid activity.

Animals↗