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Biomedical subjects

R K Shrivastava

Publications and source records attributed to R K Shrivastava.

9 recordsLinked to original sources

Clozapine in tardive dyskinesia.

Clozapine, which has had limited clinical testing in the U.S.A., was evaluated in 12 chronic schizophrenic patients with tardive dyskinesia. Its antipsychotic activity was again demonstrated and it suppressed the symptoms of tardive dyskinesia with a marked rebound occurring in these symptoms when it was withdrawn; there was no rigidity or other Parkinsonian symptoms. However, out of a total of 12 patients, neutropenia (800 and 1120) occurred in two patients, convulsion in one patient, marked withdrawal effects in three patients, and a hypotensive collapse with atrial fibrillation in one patient. If these adverse effects are confirmed in a larger sample size, then despite the novel desirable effects of clozapine it would seem unlikely that it will gain widespread or routine use.

Adult

Studies on the cholesterol synthesis in the human adipose tissue. II. Mechanism of metabolic shifts and regulation of cholesterol through ascorbic acid.

Ratios of yields of cholesterol in different media with different metabolites (200 estimations) show that if the initial normal quantity in a system is X, glucose makes it 4X which is then reduced by the amino acids and ascorbic acid. Alanine, Serine, Threonine, Cysteine, Cystine and Lysine reduce it to 2X. Glycine, Valine, Leucine, Aspartic, Phenylalanine, Tyrosine, Tryptophan roughly increase it to 6X. Other amino acids are intermediate between the above sets. Balanced amino acids and fatty acids keep up the glucose value 4X but the individual amino acids behave as above. Ascorbic acid reduces the quantity of cholesterol everywhere from one third to one half bringing it back to normal X. Since it is not directly involved in the cholesterol synthesis, it must be acting through the pyridine nucleotides. The interesting feature is that the C/H ratio in the amino acids corresponds to the yield of cholesterol with respect to glucose saline yield = 1. Mechanism of metabolic shifts has been discussed on the empirical basis as also on the basis of the change in ratios of NAD+ (NADP+) to NADH2 (NADPH2) through ascorbic acid.

Acetates

3:4-Dihydroxyphenzylalanine and biosynthesis of cholesterol in vivo and in vitro experimental studies.

In vitro incubation of 24 amino acids with frog liver homogenate shows 4 grades of cholesterogenic values. 1. Alanine, Phenylalanine, Tyrosine and DOPA give positive results. Other amino acids were able to sustain the original amounts of cholesterol to different proportions e.g. 2. Aspartic acid, Proline and Valine (50%). 3. Sodium Acetate, Arginine, Cysteine, Leucine, Norleucine, Methionine and Serine (more than 50%). 4. Aminobutyric, Glutamic, Glycine, Histidine, Hydroxyproline, Isoleucine, Lysine, Ornithine, Threonine and Tryptophan (less than 50% to negligible). DOPA gives the maximum yield of 73.1% It also shows high cholesterogenic values in different organs both in vitro and in vivo. It is thus a major precursor of cholesterol in animal tissues. Scheme of biosynthesis of cholesterol from DOPA ARE GIVEN ON THE BASIS OF KNOWN FACTS. A postulated scheme of direct synthesis of sterid molecule from DOPA is also provided. DOPA also showns sympathomimetic effects upon subcutaneous administration and blood cholesterol is reduced to more than 50%. Although there are numerous publications detailing the various aspects of biosynthesis of cholesterol and hyper and hypo-cholesterolemia yet the exact realtionship between the amino acids and cholesterol synthesis is not properly understood. Recent publications of Shrivastava (1975 a,b,c) have aspecially drawn attention to the high cholesterogenic effects of 3:4-dihydroxyphenylalanine. This work presents evidence that DOPA is infact a major and potential source of cholesterol not only in liver but in other animal tissues as well.

Amino Acids

Investigation of the presence of chromaffin tissue in the ovary of the percoid teleost fish, Nandus.

The ovary of Nandus shows chromaffin tissue at different sites below the tunica albuginea, along the ovigerous lamellae and near the oocytes. The tissue can be mistaken for interstitial cells as it shows intense sudanophilia. That it is chromaffin tissue is confirmed by its positive reaction to all the usual histochemical tests for chromaffin. This tissue may represent some stage in the development of "corpora lutea".

Animals

Studies on sterol/steroid biosynthesis from 3:4 dihydroxy phenyl alanine.

Homogenated tissue of gonads of Rana tigrina were incubated in Young's Ringer solution containing 5 mg of 3:4 dihydroxy phenylalanine. An increase in the cholesterol and neutral-17-ketosteroids was found when compared with the control. Perfusion of ovary with DOPA gave similar results. However, there was a sharp drop (greater than 50%) in the cholesterol contents of the kidney and suprarenal under similar conditions. A postulated scheme of steroid biosynthesis from DOPA is given.

17-Ketosteroids