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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 361 records · Page 20Linked to original sources

Effect of fatty acids on the permeation of melatonin across rat and pig skin in-vitro and on the transepidermal water loss in rats in-vivo.

Transdermal delivery of melatonin would be advantageous in the treatment of sleep disorders considering the short biological half-life of melatonin and its variable bioavailability via the oral route. This study looked at suitable penetration enhancers for the transdermal permeation of melatonin. The permeation of melatonin was enhanced by all saturated and unsaturated fatty acids across both rat and porcine skin. There was a parabolic relationship between the carbon chain length of saturated fatty acids and the enhancement of melatonin permeation across rat and porcine skin. For rat skin, the maximum flux was observed with undecanoic acid (45.33 microg cm(-2) h(-1)) which enhanced the flux of melatonin 8.6 times compared with the control, whereas lauric acid produced the maximum flux of melatonin (24.98 microg cm(-2) h(-1); 4-7 times) across porcine skin. An increase in the number of double bonds in cis-9-octadecanoic acid increased the flux of melatonin across rat skin. In contrast, with porcine skin, the flux of melatonin decreased as the number of double bonds increased, although the flux values were not statistically significant. Treatment of rats with undecanoic acid, oleic acid and linolenic acid for 3 h using Hill top chamber enhanced the transepidermal water loss significantly. The maximum transepidermal water loss was observed with undecanoic acid and linolenic acid among saturated and unsaturated fatty acids, respectively. Nonanoic acid and myristic acid did not cause a significant change in the transepidermal water loss. The enhancement effect of saturated fatty acids on the permeation of melatonin was dependent on the chain-length of the fatty acid in both rat and porcine skin. While an increase in the number of double bonds in the fatty acid increased the flux of melatonin in rat skin, no significant difference in the flux was observed with porcine skin. The permeation enhancement of melatonin by saturated and unsaturated fatty acids across rat skin was significantly higher than that of porcine skin. A positive correlation was observed between the permeation enhancement effect of the fatty acids across rat skin in-vitro and the transepidermal water loss in rats in-vivo, suggesting that there is a similarity in the mechanism by which fatty acids enhance the permeation of melatonin and in the enhancement of transepidermal water loss. We conclude that saturated fatty acids such as undecanoic acid or lauric acid which showed maximum permeation across rat and porcine skin, respectively, may be used as potential penetration enhancers in the development of a transdermal delivery system for melatonin.

Acids, Acyclic↗

Possible role of cardiac mast cells in norepinephrine-induced myocardial preconditioning.

The present study was designed to investigate the role of cardiac mast cells in the cardioprotective effect of norepinephrine-induced preconditioning. Isolated rat heart was subjected to 30 min of global ischemia followed by 30 min of reperfusion. Both ischemic and norepinephrine (100 microM) preconditioning markedly reduced ischemia-reperfusion-induced release of lactate dehydrogenose (LDH) in the coronary effluent and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Ischemic and norepinephrine preconditioning also significantly reduced ischemia-reperfusion-induced release of mast cell peroxidase (MPO), a marker of mast cell degranulation. However, MPO release increased immediately after ischemic or norepinephrine preconditioning. Histological study with ruthenium red (0.005%) staining confirmed cardiac mast cell degranulation in ischemic and norepinephrine preconditioned isolated rat hearts. These findings tentatively suggest that pharmacological preconditioning with norepinephrine produces a cardioprotective and antiarrhythmic effect similar to ischemic preconditioning through degranulation of resident cardiac mast cells.

Animals↗

Studies with lysine N6-hydroxylase. Effect of a mutation in the assumed FAD binding site on coenzyme affinities and on lysine hydroxylating activity.

The proposed FAD binding site of L-lysine N6-hydroxylase (EC 1.14.13.99) exhibits an unusual proline in a position where a highly conserved glycine is found in other FAD dependent hydroxylases. We have studied the role of this proline by mutating it to glycine in [P14G]aerA, which was expressed in Escherichia coli M15-2 and purified to homogeneity. The mutation has marked effects on the affinities of the cofactors FAD and NADPH as well as the substrate, lysine. Compared to the wild-type enzyme, the activity vs. pH profile of the mutant protein indicates a shift of the apparent pK'(a)s (7.8 and 8.7 for wild-type and 6.8 and 7.7 for the P14G-mutant enzyme) and of the activity maximum (pH 8 for wild-type and pH 7 for the P14G-mutant enzyme). While the activity of the mutant enzyme is much lower under conditions found to be optimal for the wild-type enzyme, adjustment of substrate and cofactor concentrations and pH leads to comparable activities for the mutant enzyme. These results suggest that the proline fulfils an important structural role in the proposed FAD binding site.

Amino Acid Sequence↗

Parsing silhouettes: the short-cut rule.

Many researchers have proposed that, for the purpose of recognition, human vision parses shapes into component parts. Precisely how is not yet known. The minima rule for silhouettes (Hoffman & Richards, 1984) defines boundary points at which to parse but does not tell how to use these points to cut silhouettes and, therefore, does not tell what the parts are. In this paper, we propose the short-cut rule, which states that, other things being equal, human vision prefers to use the shortest possible cuts to parse silhouettes. We motivate this rule, and the well-known Petter's rule for modal completion, by the principle of transversality. We present five psychophysical experiments that test the short-cut rule, show that it successfully predicts part cuts that connect boundary points given by the minima rule, and show that it can also create new boundary points.

Adult↗

Completing visual contours: the relationship between relatability and minimizing inflections.

Visual completion is a ubiquitous phenomenon: Human vision often constructs contours and surfaces in regions that have no sharp gradients in any image property. When does human vision interpolate a contour between a given pair of luminance-defined edges? Two different answers have been proposed: relatability and minimizing inflections. We state and prove a proposition that links these two proposals by showing that, under appropriate conditions, relatability is mathematically equivalent to the existence of a smooth curve with no inflection points that interpolates between the two edges. The proposition thus provides a set of necessary and sufficient conditions for two edges to be relatable. On the basis of these conditions, we suggest a way to extend the definition of relatability (1) to include the role of genericity, and (2) to extend the current all-or-none character of relatability to a graded measure that can track the gradedness in psychophysical data.

Humans↗

Transferrin As A targeting ligand for liposomes and anticancer drugs.

In cancer treatment, one of the approaches is targeting of the drug to tumor cells via receptor specific ligands. Transferrin (molecular weight 80,000) has been used as a ligand for delivering anticancer drugs or drug containing liposomes mostly due to the increased number of transferrin (trf) receptors found on tumor cells as compared to normal cells. Transferrin was linked to methotrexate (MTX) containing small unilamellar liposomes and its activity was compared to antitransferrin receptor antibody (7D-3) linked to MTX liposomes. In each of these conjugates, the method of coupling was the same and a disulphide linkage was formed between the ligand and MTX liposomes. No significant differences in the potency of 7D-3 conjugate or trf conjugate with MTX liposomes were observed in studies performed in vitro against various human tumor cell lines (Hela, KB and Colon). Trf was also linked to adriamycin via a schiff base which was formed by using glutaraldehyde. This conjugate was found to be effective in vitro against various human tumors (Lovo, HL-60, SW 403 and Hep2) and also in vivo against H-mesothelioma tumors. Transferrin receptor has also been used for gene delivery. Gene delivery to K562 haematopoietic leukaemic cells was achieved by using a transferrin-polycation (poly-L-lysine or protamine) conjugate. This review will cover the various important applications of transferrin based drug delivery formulations in the chemotherapy of cancer and the related work performed in our and other laboratories.

Animals↗

Bilateral ovarian stromal hyperplasia concealing a nonhilar, pure stromal-Leydig cell tumor. A case report.

BACKGROUND: Of ovarian stromal tumors containing Leydig cells, nonhilar, pure stromal-Leydig cell tumor is rare. CASE: An obese, diabetic, borderline hypertensive 41-year-old woman with a five-year history of oligomenorrhea and amenorrhea presented with complaints of masculinization. Physical examination revealed hirsutism and an enlarged clitoris. The only abnormal serum marker was elevated testosterone. At laparotomy both ovaries were enlarged and suspected to have bilateral stromal hyperthecosis. Histology revealed stromal hyperplasia along with a 1.5-cm, testosterone-producing pure stromal-Leydig cell tumor of the right ovary. CONCLUSION: Bilateral ovarian enlargement secondary to stromal hyperplasia in patients with masculinizing signs can conceal a small, unilateral pure stromal-Leydig cell tumor.

Adult↗

A comparison of antigen dipstick assays with polymerase chain reaction (PCR) technique and blood film examination in the rapid diagnosis of malaria.

Early diagnosis of malaria for military personnel training in the field is crucial in providing proper treatment for the infected and in taking appropriate preventive measures for the non-infected. Present preliminary diagnosis of malaria in the field depends on the clinical symptoms of the patients and there is a need for rapid diagnosis of malaria in the field. The presence of drug-resistant strains of the Plasmodium species in the region also increases the urgency of finding a quick and sensitive way of identifying the different strains. This study evaluated current methods available for the diagnosis of Plasmodium falciparum and Plasmodium vivax. The dipstick assays, the ParaSight F test and the OptiMAL malaria rapid test were compared with the methods of microscopic examination of blood film and polymerase chain reaction (PCR). On comparison to the blood film and PCR methods, the ParaSight F test has specificity of 98.6% and sensitivity of 91% for P. falciparum detection. The OptiMAL malaria rapid test has a specificity of 100% and 98.6% and sensitivity of 92.8% and 92.6% for P. vivax and P. falciparum detection respectively. We conclude that both tests are suitable for use for rapid malaria diagnosis in the field but the OptiMAL rapid malaria test, which can detect both vivax and falciparum malaria, would be more useful.

Animals↗

Reflex changes in heart rate during chemoreceptor stimulation in monkeys.

The changes in heart rate induced by the stimulation of arterial chemoreceptors by apneic asphyxia and left atrial - intracarotid injections of sodium cyanide were investigated in anesthetized artificially ventilated and paralysed monkeys. Apneic asphyxia and sodium cyanide injection caused tachycardia, bradycardia, or both in monkeys paralysed with decamethonium bromide and tachycardia only, in monkeys paralysed with gallamine. In both groups, the tachycardia was abolished by prior administration of propranolol and the bradycardia, by atropine. Prior ventilation with 100% O2 abolished the heart rate responses produced by apnea. Recording of phrenic efferent activity showed that the neural discharge increased in response to apneic asphyxia and sodium cyanide injections. It remained so during the manifestation of tachycardia, bradycardia, or no change in heart rate, suggesting that even though "higher centres" may have an important influence in the heart rate responses elicited, central respiratory drive may not be the only mechanism. The present results show that in the nonhuman primate, arterial chemoreceptor stimulation elicits both cardioacceleratory and cardioinhibitory reflexes, and the net effect of their stimulation on heart rate depends upon the balance between these opposing mechanisms.

Adrenergic beta-Antagonists↗

Testicular biopsy in infertility.

Eighty-eight infertile couples attended the infertility clinic. Semen analysis was abnormal in 64 cases. The cases were divided into 3 groups according to sperm count:Group I (count zero), group II (count < 20 million/ml) and group III (20-50 million/ml). The morphology of testicular biopsy categorised into 5 groups were normal--10(15.63%), hypospermatogenesis--42(65.63%), the Sertoli cell only syndrome--2(3.13%), maturation arrest--2(3.13%) and tubular hyalinization--8(12.50%). Quantitative analysis of biopsies was done using mean Johnson score(MJS) and Silber score(SS). The morphology in any single section was not uniform but of mixed type. Normal spermatogenesis in azoospermics indicated bilateral ductal obstruction. As compared to MJS, SS showed a more direct correlation between number of mature spermatids per tubular cross section and sperm count in unobstructed cases.

Biopsy↗

Utility of bilateral coronary injections during complex coronary angioplasty.

We describe a technique useful in complex coronary interventions wherein timed bilateral contrast injections are given in both coronary arteries. This technique is useful in chronic total occlusions in which the distal coronary vessel is not visualized except by collateral filling via the contralateral artery. This technique was applied in 12 patients; 11 with native coronary occlusion and one in whom the target site was visualized by contrast injections into a vein graft supplying competitive flow to an otherwise patent native vessel. With this technique, the distal coronary artery segment can be better visualized, which helps to aim and track the guide wire across the occluded segment.

Aged↗

Effect of phenobarbitone administration to pregnant rats on anxiety in offsprings.

Adults Charles-Foster rats were prenatally treated to phenobarbitone (10 mg/kg, i.p.) from day 13 to 21 of gestation, this being the critical period of neural development. Pregnant control rats were similarly treated with equal volume of vehicle. Adult rat offsprings at 8-9 weeks of age were subjected to open-field exploratory behaviour, elevated plus-maze and elevated zero-maze tests. The rat offsprings displayed significantly increased ambulation and rearings in an open-field arena when compared to control offsprings whereas self-grooming and faecal droppings remain unchanged. On elevated plus-maze test these prenatally treated rat offsprings spent significantly less time on open arms and more time and more number of entries in enclosed arms as compared to controls. Prenatally exposed rats also showed significant less time on open arms, less number of head dips and stretched attend postures on elevated zero-maze test indicating increased anxiogenic behavioural pattern in these animals. The results suggest that prenatal exposure to phenobarbitone leaves a lasting effect on the anxiety state of the offsprings.

Animals↗