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Biomedical subjects

S K Agarwal

Publications and source records attributed to S K Agarwal.

At least 19 recordsLinked to original sources

Structure of lansimide 2, a product from Clausena lansium.

The natural product lansimide 2 is a 1:1 mixture of two different cyclic amides, C18H17NO2.C18H19NO3. The mixture crystallizes as a molecular pair in the centrosymmetric space group P21/n. M(r) = 576.69, monoclinic, a = 20.151 (2), b = 6.2984 (4), c = 24.051 (2) A, beta = 104.339 (8) degrees, V = 2957.4 A3, Z = 4, Dx = 1.30 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 6.1 cm-1, F(000) = 1224, T = 163 (1) K, R = 0.033, wR = 0.034 for 5002 observed reflections.

Lactams

Interaction of putative neurotransmitters in rostral ventrolateral medullary cardiovascular neurons.

As recent immunohistochemical evidence has shown the coexistence of putative neurotransmitters in the rostral ventrolateral medulla (RVLM), we have investigated the possibility that there may be an interaction of putative transmitters on the firing frequency of cardiovascular neurons in the RVLM. Extracellular activity was recorded from 37 spontaneously firing units in the right RVLM of urethane anaesthetized and artificially ventilated rats. Nine of these units were classified as cardiovascular neurons because: (i) they were silenced by baroreceptor activation (1-3 micrograms phenylephrine i.v.); and (ii) they showed rhythmicity of their spontaneous activity in synchrony with the cardiac cycle. Microiontophoresis of combinations of near threshold amounts of L-glutamate (GLU; 10 nA), acetylcholine (Ach; 30 nA) and substance-P (SP; 60 nA) showed a synergistic interaction of these substances with one another in eliciting changes in firing frequency of cardiovascular neurons. These results show that GLU and Ach, GLU and SP and Ach and SP interact synergistically to influence the firing frequency of cardiovascular neurons in the RVLM and suggest that these substances play a physiological role in the neural control of the circulation.

Acetylcholine

Electrical stimulation of nucleus tractus solitarius excites vagal preganglionic cardiomotor neurons of the nucleus ambiguus in rats.

Recent evidence indicates that the cell bodies of vagal cardioinhibitory neurons are located principally in the external formation of the nucleus ambiguus (NA). As activation of baroreceptor afferent fibers projecting to the nucleus tractus solitarius (NTS) elicits a decrease in heart rate it is likely that there is a connection between the NTS and NA. To test the hypothesis that stimulation of the NTS can excite vagal preganglionic cardiomotor neurons (VPCN) in the NA, activity from 78 neurons in the NA was recorded extracellularly before and during stimulation of a depressor site in the NTS (1 Hz, 0.1 ms) in urethan anesthetized and artificially ventilated male Wistar rats. Sixteen neurons were characterized as vagal preganglionic cardiomotor neurons (VPCN) because they were excited by baroreceptor activation (1-3 micrograms phenylephrine i.v.) and showed rhythmicity of their spontaneous activity in synchrony with the cardiac cycle. Stimulation of the NTS increased the firing rate of all these VPCN. The remaining 62 neurons could not be considered as VPCN because they either had respiratory rhythmicity or were not sensitive to baroreceptor activation, or they were sensitive to baroreceptor activation but did not display cardiac cycle related rhythmicity. These results provide evidence for the existence of an excitatory pathway from NTS to vagal preganglionic cardiomotor neurons in the NA.

Animals

Early evidence of beneficial effects of chordal preservation in mitral valve replacement on left ventricular dimensions.

Earlier authors have shown the improved left ventricular (LV) function after chordae-preserving mitral valve replacement (MVR) in follow-up studies. Seventy-nine consecutive patients undergoing MVR were studied preoperatively and pre-discharge with M-mode and two-dimensional Color Doppler echocardiography for early LV morphometric changes. Conventional MVR was performed in 42 patients (Group 1) and the posterior leaflet-chordae-papillary muscle complex was preserved in 37 patients (Group 2). Both cohorts were similar in age, sex, preoperative NYHA class and valve pathology. Four St. Jude bioprostheses, 9 Medtronic and 66 Sorin prostheses were implanted. The intraoperative and perioperative management protocol was uniform for both groups. The median left atrial dimension in both groups decreased to better physiological levels (53 to 46 mm in group 1, 52.5 to 46 mm in group 2). The median LV enddiastolic dimension increased from 47 to 48 mm in group 1 while it decreased from 56.5 to 49 min in group 2. The median LV endsystolic dimension remained unchanged in group 1 but decreased in group 2 (37.6 to 36 mm). Echocardiographic documentation of such early changes in the LV dimensions after modified MVR indicates that the beneficial effects of chordal preservation become evident early in the postoperative period and may explain the improved perioperative LV function after modified MVR compared to conventional MVR.

Adolescent

Structure-activity relationship in buffalo spleen cathepsin B.

Effect of pH, urea, and guanidine hydrochloride on the activity and structure of buffalo spleen cathepsin B was investigated. At alkaline pH, there was an irreversible loss of the structure as well as the activity of the buffalo enzyme. At acidic pH, however, the inactivation of the enzyme was reversible. The enzyme reversibly lost most of its activity at denaturant concentrations which did not cause a significant change in its secondary structure. The inactivation could be attributed to minor perturbations in the environment of the amino acid residue(s) at and/or around the active site of the enzyme. High urea/guanidine hydrochloride concentrations leading to the structural changes in cathepsin B made the inactivation process irreversible.

Animals

Salting-out behaviour of the domains of ovomucoid.

The solubility of ovomucoid and of four fragments comprising domain I, I+II, and III of the protein in concentrated ammonium sulphate solution were studied at different pHs (25 degrees C) and at various temperatures (pH 7.0), and the salting-out parameters Ks and beta were determined for the five proteins. The aqueous solubilities of ovomucoid and the four fragments were highly dependent on temperature which causes structural alteration due to thermal unfolding of the proteins. The values of KS and beta for domain III and domain II+III at different pHs were similar to those of other globular proteins whereas those of ovomucoid and domain I and domain I+II were atypical. They were explained in terms of the lack of structural stability and the presence of carbohydrate moieties in domains I and II.

Ammonium Sulfate

Colonic immunity in patients and amoebic liver abscess.

Secretory immunoglobulin A (S-IgA), coproantibody titre (antiamoebic) and IgA, IgG, IgM immunocytes in rectal mucosa were studied in 13 patients with amoebic liver abscess (ALA) prior to and 4-6 weeks after completion of antiamoebic therapy. Ten asymptomatic Entamoeba histolytica cyst passers and 17 healthy age and sex matched volunteers served as controls. Fecal S-IgA levels and counts of IgA bearing immunocytes in mucosa were significantly higher in patients with ALA and cyst passers as compared to healthy controls and showed a significant fall after treatment. Fecal antiamoebic antibodies were high in cyst passers and in cases of ALA after treatment. Raised levels of S-IgA and IgA class immunocyte counts probably indicate a local mucosal immune response directed at containing the infection.

Antibodies, Protozoan

Kinetics of specific IgM in patients of hepatic amoebiasis.

Entamoeba histolytica (EH) specific IgM was measured in 54 patients with diagnosed amoebic liver abscess (ALA), 13 with non-suppurative hepatic amoebiasis (NSHA) and 50 controls. The mean levels of EH specific IgM, estimated by ELISA were significantly raised in patients of invasive amoebiasis (both ALA and NSHA) compared to controls (P less than 0.05). EH specific IgG was also raised in both groups of patients. Follow up of patients with ALA showed a significant decline (P less than 0.05) in the specific IgM levels three months after treatment while the specific IgG antibodies persisted in high titres (1:160). Only four patients of NSHA could be followed up and all showed a decline in specific IgM levels. Raised specific serum IgM seems to be an indicator of active (invasive) amoebiasis.

Adult

Auxotyping of Neisseria gonorrhoeae as an additional epidemiological marker.

Auxotypes and penicillin sensitivity of 102 strains of N. gonorrhoeae were studied. Ten distinct auxotypes on the basis of growth requirement to seven amino acids were observed. The commonest pattern seen was zero auxotype (33.3%), followed by auxotype requiring proline (18.6%). MIC of 72 (71.5%) strains ranged from < 0.003 IU/ml to 0.062 IU/ml of benzyl penicillin. MIC of the other 30 (29.5%) strains was found to be > or = 0.125 IU/ml, indicating penicillin resistance. None of the strains were penicillinase producers. A case of reinfection was also detected on the basis of change in auxotype pattern.

Amino Acids

Sucralfate versus ranitidine in non-ulcer dyspepsia: results of a prospective, randomized, open, controlled trial.

In an open trial, 100 patients with non-ulcer dyspepsia were randomized to receive either ranitidine 150 mg twice daily (n = 47) or sucralfate 1 g four times a day (n = 53) for four weeks. An 'intention to treat' analysis revealed that global relief in symptoms was significantly more frequent in the sucralfate group than in the ranitidine group after two weeks (77.4% vs 59.6%; p less than 0.05) and four weeks (86.8% vs 63.8%; p less than 0.001) of treatment. It is concluded that sucralfate is superior to ranitidine in providing symptomatic relief in patients with non-ulcer dyspepsia.

Adult

Microinjection of glycine into the nucleus ambiguus elicits tachycardia in spinal rats.

In 30 male Wistar spinal (C1) rats, anaesthetized with urethane and artificially ventilated, experiments were done to study the effect on heart rate (HR) and arterial pressure (AP) of microinjection of the inhibitory amino acid glycine (Gly) into the nucleus ambiguus (NA). L-Glutamate (Glu; 1.5 nmol) was microinjected into the region of the right NA to search for sites from which decreases in AP and HR could be elicited. The decreases in HR were found to be 73.1 +/- 7.0 bpm (n = 30). No changes in AP were observed. Microinjection of Gly (1 M; 2-20 nmol in 2-20 nl; n = 12) elicited a dose dependent increase in HR with no changes in AP. Microinjection of Gly 1-2 min before microinjection of Glu in 7 sites reduced significantly (P less than 0.05) the decrease in HR elicited by Glu from 87.0 +/- 27.3 bpm to 17.7 +/- 7.2 bpm. Increases in HR elicited by Gly in the right NA of another 12 rats were not affected significantly by prior microinjection of the Gly antagonist strychnine hydrochloride (30-90 pmol in 10-30 nl in one group of animals, n = 6; and 2.5 nmol in 50 nl in another group, n = 6). In addition, to determine whether the effects of Gly were caused by actions on N-methyl-D-aspartate (NMDA) receptors, kynurenic acid (KYN; 4.5 nmol in 30 nl) was microinjected into the right NA of 6 rats prior to microinjection of Gly. KYN failed to block the response to Gly microinjection and instead potentiated the HR increase elicited by Gly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Enkephalins, substance P and acetylcholine microinjected into the nucleus ambiguus elicit vagal bradycardia in rats.

Little is known about putative transmitters in the nucleus ambiguus (NA) mediating parasympathetic control of the heart, although Met-enkephalin (m-ENK), Leu-enkephalin (l-ENK), substance P (SP) and acetylcholine (Ach) have been detected in the cell bodies and fibers of this nucleus. The effects of these substances on arterial pressure (AP) and heart rate (HR) were studied by microinjecting them (4-20 nl) into the NA. Experiments were done in 26 spinal (high cervical) rats that were anesthetized with urethane and artificially ventilated. L-Glutamate (GLU) was microinjected into the right NA to identify the location of cell bodies from which decreases in HR and AP could be elicited. m-ENK, l-ENK, SP or Ach was then microinjected into these sites. Microinjection of 1 nmol of GLU elicited significant decreases in HR (-72.2 +/- 9.7 bpm, n = 15) which were not accompanied by significant decreases in mean AP. Microinjection of m-ENK (15-200 pmol; n = 7), l-ENK (15-200 pmol; n = 6), SP (0.9-15 pmol; n = 7) and Ach (2.0-20 pmol; n = 7) into the NA decreased HR in a dose-dependent manner but did not affect AP. The magnitudes of HR responses to m-ENK, l-ENK, SP and Ach were smaller but of longer duration than the changes in HR to microinjection of GLU. These results suggest a physiological role for GLU, enkephalins, SP and Ach in the vagal control of HR mediated by the NA.

Acetylcholine

Monosynaptic connection from caudal to rostral ventrolateral medulla in the baroreceptor reflex pathway.

Experiments were done to test the hypothesis that caudal ventrolateral medulla (CVLM) neurons excited by activation of arterial baroreceptors and by stimulation of depressor sites in the nucleus tractus solitarii (NTS) project monosynaptically to the rostral ventrolateral medulla (RVLM). In urethan anaesthetized and artificially ventilated rats we recorded extracellular activity from 46 spontaneously firing units in the CVLM. Twenty of these units were excited by baroreceptor activation (1-3 micrograms phenylephrine i.v.) and of these 6 were excited (mean latency of 9.8 +/- 2.3 ms) by single pulses (0.1 ms, 30 +/- 8.3 microA) delivered once per second to a depressor site in the ipsilateral NTS. These 6 units were also antidromically activated with a latency of 4.1 +/- 0.12 ms by stimulation of a pressor region in the ipsilateral RVLM. These results provide evidence for the existence of an excitatory projection from the NTS to the CVLM which, in turn, projects monosynaptically to sympathoexcitatory neurons in the RVLM.

Action Potentials