Biomedical subjects
Publications and source records attributed to T Hussain.
We demonstrate by an ELISA the presence of antibodies in human filarial sera that react with diethylcarbamazine (DEC); they appear to be primarily filarial antibodies cross-reacting with DEC skeleton, since affinity-purified DEC antibodies strongly react with Wuchereria bancrofti microfilariae. These observations indicate a possible antigenic mimicry between the drug and some parasite component.
Explore the source record for details and available documents.
The effect of a supplementary food mix prepared from roasted mungbean, groundnuts, and sugars on maternal nutrition and birth weight of newborns was studied. The results indicated that supplementary food provided to the pregnant women had a significantly positive effect on the birth weight of newborns. In addition, a significantly higher weight gain by the mothers was observed as compared to the control group.
Cd2+ (0.4 mg/kg) administration to growing rats (45 +/- 5 g) intraperitoneally, daily for 30 days was found to decrease the activity of superoxide dismutase (SOD) in all the brain regions, except hippocampus. The concentrations of lipid peroxides were significantly elevated in the cerebellum, cerebral cortex, corpus striatum and midbrain. A 100% inhibition in SOD activity was observed by 14 microM and 50 microM of Cd2+ in bovine blood and rat brain preparations, respectively. Cadmium-induced strong inhibitory effect on brain and purified bovine blood SOD suggested a direct effect of the metal on enzyme molecule. Furthermore, in vitro addition of a wide range of Cd2+ (1-100 microM) increased the rate of lipid peroxidation (LPO) reaction in fresh brain homogenate, however, did not affect boiled homogenate. The studies on LPO in reconstituted homogenate resulting from mixing of fresh and/or heated different subcellular fractions indicated the presence of some heat-labile Cd2+ -sensitive factor in 15000 x g pellet fraction. It is suggested that Cd2+ directly and indirectly through inhibition of SOD, increases the LPO of cell membranes and thus produces damage to the associated physiological functions leading to central nervous dysfunctions.
Rat striatal synaptosomes (P2-fraction) were subjected to lipoperoxidation by the addition of 120 microM Fe2+ and 200 microM ascorbic acid. This preparation (pretreated synaptosomes) was used to investigate the interaction of Pb2+ and Mn2+ on the uptake of tritiated catecholamines, Na+, K+-ATPase activity and malondialdehyde (MDA) formation in order to understand the mechanism of enhanced neurotoxicity by concurrent exposure to these metals. The combination of Pb2+ and Mn2+ (25 microM + 100 microM, respectively) produced a significant increase in the uptake of 3H-Dopamine only in the untreated synaptosomes. No significant effect was noted on the uptake of 3H-Norepinephrine in either pretreated or untreated synaptosomes. However, the combination of Pb2+ and Mn2+ produced a pronounced decrease in the activity of Na+, K+-ATPase, but the magnitude of the change was the sum of the individual metal effects. Metal interaction did not produce any significant change in the formation of MDA compared to the control (without addition of metals). These results indicate that Pb2+ and Mn2+ interaction may produce inhibition in the activity of transport ATPase in both the preparation of synaptosomes, with more pronounced effect of synaptosomes subjected to lipoperoxidation and these changes may be responsible for the disruption in the physiology of nerve impulse transmission.
Intraperitoneal administration of cadmium acetate (Cd2+, 0.4 mg/kg) to rats daily for 30 days was found to inhibit the activity of superoxide dismutase (SOD), to increase the endogenous levels of lipid peroxides and lipid peroxidation in the liver and the kidney tissues. Addition of varying concentrations of Cd2+ (10-100 microM) in vitro also inhibited SOD in both the tissues. It appears that the inhibition of SOD could be due to direct interaction of Cd2+ with the enzyme molecule. Lipid peroxidation reaction was also increased after addition of Cd2+ to fresh homogenate of these tissues, however, it did not produce any effect in heated homogenates in in vitro experiments. It indicated that Cd-induced elevation in lipid peroxidation may not be only due to the possibility of higher level of superoxide radicals resulting from inhibited superoxide dismutase but could also be as a result of direct action of Cd2+ on the peroxidation reaction. Thus, the possibility of involvement of free radical damage to the membrane structures in Cd toxicity has been demonstrated in these experiments.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Diabetic rats (alloxan diabetes) were exposed to cadmium (2 mg kg-1 i.p.) daily for 21 days to investigate the levels of blood glucose, biogenic amines and iron, copper, zinc and cadmium in the brain. Cadmium exposure to diabetic rats produced a significant exacerbation in the hyperglycemic effect and accumulation of cadmium in the blood compared with that observed after diabetes or cadmium exposure alone. The elevation in the levels of brain dopamine and 5-hydroxytryptamine were also more pronounced in cadmium-exposed diabetic rats compared with either cadmium exposure or diabetes alone. Cadmium exposure to diabetic rats also produced significant changes in the concentrations of copper in the blood. These results indicated enhanced cadmium toxicity in diabetic rats.
Explore the source record for details and available documents.
Three diets based on rice-dehulled mungbean, rice-minced meat and rice-mungbean with hull were tested with infants 11 to 20 months of age using a short term nitrogen balance technique. The results indicate that with isocaloric and isonitrogenous intake, all the subjects given either of the three diets were in positive nitrogen balance. The protein quality, in terms of nitrogen absorption and true digestibility, of rice-meat diet was superior to that of rice-bean diets. Among the rice-bean diets, it was noted that rice-mungbean with hull had a lower digestibility as compared to rice-dehulled mungbean diet. The poor digestibility of rice-mungbean with hull diet is the first limiting factor in its utilization by infants. Dehulling of mungbean before cooking is recommended for preparing weaning food for infant feeding.
The nuclei of unfixed isolated rabbit neurons cleared on incubation with DNAse (10 mg/ml), but not RNAse (10 mg/ml). The nuclei stained for DNA with eight chromosomal or nuclear stains more intensely than the cytoplasm, and less intensely after treatment with DNAse (10 mg/ml). On the other hand, when the whole tissue was embedded and sectioned, DNA did not appear to be stained in the nucleus; the nucleolus and the cytoplasm were more heavily stained than the nucleoplasm. Possible explanations for this apparent anomaly are considered. It was concluded that DNA diffused out of the nucleus during embedding and sectioning, and that the colouration of the nucleolus and cytoplasm with the eight staining systems used was due to other nucleotides present.
Explore the source record for details and available documents.
The design, synthesis, and receptor subtype binding affinities of several 2-substituted thioadenosine nucleoside and nucleotide analogues are described. Alkylation of 2-thioadenosine (1) with iodopentenylboronic acid followed by iododeboronation gave 2-((E)-1-iodo-1-penten-5-yl) thioadenosine (9). Compound 1 on treatment with 4-nitrobenzyl bromide and propargyl bromide furnished compounds 3 and 5, respectively. The 5'-monophosphate analogues of compounds 3, 5, 7, and 9 were prepared similarly using 2-thioadenosine 5'-monophosphate (2). Treatment of 1 with bromoethylamine hydrobromide provided 2-[(aminoethyl)thio]adenosine (11) which on coupling with N-succinimidyl 3-(4-hydroxyphenyl)propionate gave 2-[[[3-(4-hydroxyphenyl)propionamido]ethyl]thio]adenosine (12). Iodination of 12 gave 2-[[[3-(4-hydroxy-3-iodophenyl)propionamido]ethyl]thio]adenosine (13). Compounds 3-13 were evaluated for their affinities toward A1 and A2 adenosine receptors in rat brain cortex and striatum, respectively using [3H]DPCPX and [3H]CGS21680 as ligands. The nucleotide analogues 4, 6, 8, and 10 inhibited binding of [3H]DPCPX by 10-20% and of [3H]CGS21680 by 40-50% at a concentration of 100 microM suggesting weak affinity toward adenosine receptors. The nucleoside analogues 3, 5, 7, 9, 12, and 13 inhibited the A2 receptor binding of [3H]CGS21680 with Ki values of 1.2-3.67 microM, while A1 receptor binding of [3H]DPCPX was inhibited with Ki values 10-17 microM. The A1/A2 ratios suggest 4-8-fold A2 receptor selectivity.
A double-blind placebo-controlled study in children showed codergocrine mesylate to be effective in improving cognitive functions and behavioural symptoms associated with learning disorders. Forty randomly grouped children of either sex were given an increasing dosage of codergocrine mesylate and followed up for 12 weeks. A significant improvement was noted in speech (acquisition of new words, comprehensibility/meaningfulness of speech), sociability, attention/concentration, comprehension and memory. Improvement in behaviour (emotional lability and cooperativeness) was also noted. Problems of assessing cognitive progress in very young children with culturally appropriate methods were encountered.
Explore the source record for details and available documents.
Dopamine-induced natriuretic response which results from the activation of tubular dopamine1 (DA1) receptors is diminished in spontaneously hypertensive rats (SHR). This may be a result of alterations occurring at the receptor level and within the cellular signaling pathway which ultimately causes inhibition of Na+, K(+)-ATPase. There have been reports showing that DA1 receptor induced inhibition of Na+, K(+)-ATPase is abolished in SHR which is due to a decreased activation of PLC and PKC by dopamine. Of the mechanisms, adenylyl cyclase and phospholipase C are two known enzymes linked to DA1 receptors via G proteins. Furthermore, the involvement of phospholipase A2 (PLA2) has also been reported in this process. However, the site of defect in DA1 receptor signaling pathway in SHR is still not well understood. This report will (i) review the coupling of DA1 receptor with G proteins and their levels in Wistar Kyoto (WKY) rats and SHR and (ii) discuss studies dealing with the role of PLA2 in dopamine-induced inhibition of Na+, K(+)-ATPase in WKY rat and SHR kidneys. Fenoldopam, DA1 receptor selective agonist stimulated [35S]GTP gamma S binding in a concentration (10(-9)-10(-4) M)-dependent manner in WKY rats which was attenuated in SHR. Fenoldopam (10 microM)-induced stimulation of [35S]GTP gamma S binding was significantly reduced by a DA1 receptor selective antagonist, SCH 23390 suggesting the involvement of DA1 receptor. Furthermore, the specific antipeptides Gs alpha, and Gq/11 alpha significantly blocked fenoldopam-stimulation of [35S]GTP gamma S binding suggesting the coupling of DA1 receptor with both the G proteins. Western analysis revealed a significant decrease in Gq/11 alpha but no changes in Gs alpha in SHR compared to WKY rats. Dopamine inhibited Na+, K(+)-ATPase activity in a concentration (10(-9)-10(-5) M)-dependent manner in WKY rats while it failed to inhibit the enzyme activity in SHR. Dopamine (10 microM)-induced inhibition in Na+, K(+)-ATPase activity was significantly blocked by mepacrine (a PLA2 inhibitor) suggesting the involvement of PLA2 in dopamine-mediated inhibition of Na+, K(+)-ATPase. Arachidonic acid (AA), a PLA2 product, inhibited Na+, K(+)-ATPase in a concentration (1-100 microM)-dependent manner in WKY rats while the inhibition in SHR was significantly attenuated (IC50: 7.5 microM in WKY and 80 microM in SHR). Furthermore, lower concentration (1 microM) of AA stimulated the enzyme activity in SHR. This suggests a defect in the metabolism of AA in SHR. Proadifen (10 microM), an inhibitor of cytochrome P-450 monoxygenase (an arachidonic acid metabolizing enzyme) significantly blocked the inhibition produced by arachidonic acid in WKY rats and abolished the difference in arachidonic acid inhibition of Na+, K(+)-ATPase between WKY rats and SHR. These data suggest that (i) the reduced activation of G proteins following DA1 receptor stimulation, (ii) reduced amount of Gq/11 alpha and (iii) a defect in the AA metabolism may be responsible for the reduced dopaminergic inhibition of sodium pump activity and a diminished natriuretic response to dopamine in SHR.
Dopamine plays an important role in the regulation of renal sodium excretion. The activation of D1-like receptors located on the proximal tubules causes inhibition of tubular sodium reabsorption by inhibiting Na,H-exchanger and Na,K-ATPase activity. The D1-like receptors are linked via G proteins to the multiple cellular signaling systems namely adenylyl cyclase and phospholipase C (PLC). A defective renal dopamine receptor function exists in spontaneously hypertensive rats (SHR). In the proximal tubules of SHR, the stimulation of adenylyl cyclase and PLC caused by dopamine was significantly reduced in comparison with Wistar-Kyoto (WKY) rats. Also unlike the effects seen in WKY, D1-like receptor activation did not inhibit Na,K-ATPase and Na,H-exchanger activities in SHR. In addition, reduced quantity of Gq/11alpha proteins was detected in the basolateral membranes of SHR compared to WKY rats. Studies revealed that there may be a primary defect in D1-like receptors leading to an altered signaling system in the proximal tubules and reduced dopamine-mediated effect on renal sodium excretion in SHR. Recently, it has been shown that the disruption of D1A receptors at the gene level causes hypertension in mice. Similar to SHR, dopamine and D1-like receptor agonist failed to inhibit Na,K-ATPase activity in the proximal tubules of old Fischer 344 rats. Unlike the observations in SHR where D1-like receptors were equal to WKY rats, there is a 50% decrease in D1-like receptor number in basolateral membranes of the old rats compared to the adult rats. Dopamine was unable to stimulate G proteins in the basolateral membranes of old rats compared to the adult rats. It is suggested that a defective dopamine receptors/signaling system may contribute to the development and maintenance of hypertension. Also, the inability of dopamine to inhibit Na,K-ATPase may lead to a reduced renal sodium excretion in response to dopamine in old rats.