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Biomedical subjects

S Mahajan

Publications and source records attributed to S Mahajan.

At least 91 records · Page 5Linked to original sources

Role of calcium in regulating intracellular pH following the stepwise release of the metabolic blocks at first-meiotic prophase and second-meiotic metaphase in amphibian oocytes.

31P-NMR has been used to monitor changes in intracellular pH following the sequential release of the block at first-meiotic prophase by hormones and the block at second-meiotic metaphase by fertilization in Rana eggs and oocytes. The broad phosphoprotein signal was eliminated by a combination of spin-echo and deconvolution techniques. pHi was determined from the pH-dependent separation of intracellular Pi and phosphocreatine resonances. Agents that release the prophase block (progesterone, insulin, D-600, La3+) increased pHi from 7.38 to 7.7-7.8 within 1-3 h. Noninducers such as 17 beta-estradiol were without effect. By second-metaphase arrest (ovulated, unfertilized) the pHi had fallen to 7.1-7.2. pHi underwent a transient increase to about 7.7 within the first 30 min at fertilization, with a slow 0.1-0.2 pH unit oscillation during early cleavage. The progesterone-induced elevation of intracellular pH is not blocked by amiloride and occurs in Na+-free medium. A transient rise in pHi occurs when the prophase-arrested oocyte is transferred to Ca2+-free medium or when ionophore A23187 is added to the Ca2+-containing medium. Agents that inhibit the resumption of the first meiotic division either block the rise in pHi (procaine, PMSF) or shorten the time-course of the rise in pHi (ionophore A23187). Conditions that elevate intracellular Ca2+ levels and/or increase Ca2+ exchange produce an increase in pHi, whereas those conditions that decrease intracellular Ca2+ levels and/or exchange produce a fall in pHi within 1 h. The time-course of the increase in pHi both following release of the prophase block and at fertilization coincide with a fall in intracellular cAMP and release of surface and/or intracellular Ca2+. These results suggest that: (1) pHi is a function of cytosolic free Ca2+ levels and/or Ca2+ exchange across the oocyte plasma membrane, and (2) meiotic agonists (progesterone, insulin, D-600) and mitogens (sperm, ionophore A23187) modulate intracellular and/or membrane Ca2+ with the resulting changes in pHi and cAMP and resumption of the meiotic divisions.

Animals↗

Changes in short-latency somatosensory evoked potentials during hemodialysis in chronic renal failure.

Short-latency SEPs were monitored in eight patients undergoing hemodialysis for end-stage renal disease. The peak latencies of EP,N13, and N20 were significantly delayed compared with those of the control group. Because the interpeak latency of N13 - N20 (central conduction time) was not significantly prolonged, there could be no possible subclinical involvement of the ascending sensory fibers in the brainstem. The dialysis did alter the peak latencies of EP,N20, and interpeak latencies of EP-N13 and EP-N20; these changes, however, were not highly significant. The evoked potential changes did not correlate with the routine biochemical data. Monitoring short-latency SEP may lead to early recognition of pathologic involvement of the peripheral nervous system.

Adult↗

Leukocyte metabolism and function in uremia.

Leukocyte metabolism was studied in 13 non-diabetic hemodialysis patients, 8 clinically stable, nondiabetic transplant recipients, and 13 control subjects. Metabolic parameters included rates of oxygen consumption (nmoles/min/10(6) cells), glucose uptake, lactate production (nmoles/hr/10(6) cells), and 14C-l-glucose oxidation to 14CO2 (nmoles/hr/10(6) cells). Granulocyte metabolism was stimulated by phagocytosis of opsonized zymosan (Z) and by the membrane perturbing agent phorbol myristate acetate (PMA). Granulocyte motility in response to zymosan-activated plasma (ZAP) was also studied. Granulocytes from hemodialysis patients showed significantly impaired stimulated oxygen consumption (Z = 2.41 +/- 0.30 vs. 3.73 +/- 0.39; PMA = 2.63 +/- 0.33 vs. 3.67 +/- 0.19), resting glucose uptake (17.7 +/- 2.9 vs. 36.5 +/- 3.5), stimulated glucose uptake (Z = 44.2 +/- 7.1 vs. 71.8 +/- 5.3; PMA = 63.7 +/- 5.5 vs. 92.8 +/- 5.6), stimulated lactate production (Z = 68.4 +/- 5.1 vs. 97.5 +/- 9.3; PMA = 70.7 +/- 4.9 vs. 92.7 +/- 5.4), and ZAP-stimulated granulocyte motility (16 +/- 3 vs. 30 +/- 4 mu). Metabolic responses of granulocytes from transplant recipients were frequently intermediate between those of hemodialysis patients and controls, but not significantly different from controls. Abnormalities of glucose and oxygen metabolism in granulocytes from uremic patients may cause or contribute to granulocyte dysfunction and vulnerability to infection in such patients.

Adult↗

An intravasal non-occlusive contraceptive device in rats.

An implantable miniature biogalvanic cell was developed to kill the spermatozoa in the vas deferens by an electric current. Experiments in vitro and in vivo showed that a combination of aluminum/silver electrodes connected with platinum wires with the vas deferens fluid as n electrolyte is effective in killing spermatozoa. Female rats paired with males having biogalvanic devices in the vas deferens, which remained patent, did not produce any young.

Aluminum↗

Theoretical studies on tricyclic antidepressants: III. Analysis of stereospecificity.

By dynamic simulation of molecular structures in a digital computer, search was made for all possible ways of superposing a phenyl ring of a tricyclic antidepressant on the phenyl ring of norepinephrine. Using all available structure activity data and deductive reasoning, attempt was then made to reject all but one superposition. A significant outcome was information regarding 2-hydroxydesipramine. Although manifestly inactive when administered, this drug is likely to be potent if delivered at the neuronal site of action. From the chosen superposition a dihydroxy derivative is predicted to be even more potent if it can be endogenously generated or suitably modified to enable delivery at the site of action. Among the various superpositions obtained, it was indirectly possible to make a Monte Carlo type of conformational analysis on the side chain of norepinephrine. Previous conformational studies on norepinephrine are reviewed in this context.

Antidepressive Agents, Tricyclic↗

Theoretical studies on tricyclic antidepressants. IV. Probable submolecular topographic structures of the "amine pump" receptor.

A probable structure for the best tricyclic antidepressant with respect to inhibition of reuptake of norepinephrine into peripheral adrenergic nerve terminals has been reported. Using tha result as indicating the particular conformation in which the tricyclic antidepressant is likely to mimic the biogenic amine at the membrane "pump" receptor site, the topography of the receptor surface has been worked out by simulating space-filling models of the best inhibitors of the two types in the superposed state. With appropriate computer graphic facilities such surfaces can be used to screen other untested molecules and to predict their activity.

Animals↗

Theoretical studies on tricyclic antidepressants. I. Molecular structures.

Tricyclic antidepressants are believed to act by inhibiting reuptake of biogenic amines into the presynaptic neuron. This fundamental information can be exploited to characterize the reuptake mechanism in detail and to suggest modifications in drug structure aimed at improving therapeutic value. Knowledge of the three-dimensional geometry of tricyclic antidepressants is a prerequisite for such a research. Hence generation of possible geometries for such structures by theoretical and computer simulation methods has been attempted. Only a limited number of reasonable structures were obtained for most of the molecules, indicating that the obtained structures are likely to be close to actual structures. This has been somewhat substantiated by a study on the structure of imipramine hydrochloride by X-ray crystallographic methods.

Antidepressive Agents, Tricyclic↗

Injectable non-occlusive chemical contraception in the male-I.

A new contraceptive technique has been proposed and tested. The method uses a novel polymer which when injected into the vas deferens, lowers the pH sufficiently kill the spermatozoa passing through. The polymer itself does not degrade in the process but can be flushed out to regain fertility. Experiments carried out on rats demonstrate the efficacy of the technique so as to have non-surgical, non-occlusive and reversible male contraception.

Animals↗

Correlation of biochemical data with Apgar scores at birth and at one minute.

A prospective study of 66 unselected neonates revealed a better correlation of umbilical artery blood biochemical data with the Apgar score at birth compared with the score at 1 min. The data confirmed also that inclusion of the score for "colour" detracts from the value of the total score. An Apgar score at birth is more valuable than the score at 1 min.

Apgar Score↗