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Biomedical subjects

M Desai

Publications and source records attributed to M Desai.

At least 145 records · Page 8Linked to original sources

Dynamics of the protein metabolic response to burn injury.

The protein metabolic response to burn injury was assessed in 17 children aged 7.1 +/- 1.1 years (mean +/- SEM) and a mean burn size of 65 +/- 7% total body surface area (TBSA) during the acute, flow, convalescent, and recovery phases. Stable isotopes of leucine, valine, lysine, and urea were infused in postabsorptive patients in order to measure protein kinetics. The absolute rate of protein breakdown was assessed from the plasma flux of the essential amino acids (EAA), and the rate of urea production (Ra urea) was used as an index of net protein catabolism. Compared to values obtained in recovered patients, the plasma fluxes of all three EAAs were significantly increased (P less than .05), indicating an increased protein breakdown, during the acute, flow, and convalescent phases of injury. Ra urea, however, was only significantly increased during the flow phase (P less than .01), suggesting that protein breakdown was adequately counteracted in the acute and convalescent phases by elevations in protein synthesis but not in the flow phase. The protein kinetic response did not correlate with changes in the metabolic rate since resting energy expenditure (REE) was significantly increased above predicted levels during the acute and flow phases (by 40% and 50%, respectively), and returned to normal in convalescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Essential↗

Synthesis and biological properties of (carboxyalkyl)amino-substituted bicyclic lactam inhibitors of angiotensin converting enzyme.

Syntheses of the potent angiotensin converting enzyme inhibitor (3S)-1-(carboxymethyl)-3-[[(1S)-1-carboxy-3-phenylpropyl]amino]- 2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (4b; CGS 14831) and the related monoester prodrug (17a; CGS 14824A) are described together with preparative details for six- and eight-membered ring analogues. Inhibitory potencies and in vivo biological activity of the compounds are discussed. The data indicate that 17a has a biological profile comparable to that of enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

Bicyclic lactam inhibitors of angiotensin converting enzyme.

Syntheses of the potent angiotensin converting enzyme inhibitor 1-(carboxymethyl)-3-(mercaptomethyl)-2,3,4,5-tetrahydro-1H-1- benzazep in -2-one (4a) and the corresponding eight-membered ring analogue (4b) are described. The influence of ring size on the inhibitory potencies of these substances is discussed.

Angiotensin-Converting Enzyme Inhibitors↗

The importance of reverse triiodothyronine in hypothyroid children on replacement treatment.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) values were measured by radioimmunoassay in 40 children with congenital hypothyroidism who were being given levothyroxine (0.05-0.35 mg/day) and in 14 normal controls. In 15 of the children with hypothyroidism the treatment, judged by serum T4 and TSH values and thyrotrophin releasing hormone (TRH) test, seemed to be adequate and their mean rT3 value and rT3:T4 ratio were comparable with the controls. The remaining 25 children had a raised serum T4 and a low TSH value. Only 4 (16%) of these children had an abnormally high T3 concentration but the rT3 value was raised in 23 (92%) and their mean rT3 value and rT3:T4 ratio were significantly higher than in the control children. Less than 20% of this 'overtreated' group, however, had clinical hyperthyroidism. We suggest that in patients on T4 replacement treatment the peripheral thyroid homeostatic mechanisms produce larger amounts of rT3, thereby preventing high T3 values where serum T4 values are raised. This may explain why the 'overtreated' children showed no clinical evidence of hyperthyroidism. These findings emphasise the protective and selective role of peripheral monodeiodination.

Adolescent↗

Synthesis and biological properties of thiophene ring analogues of mianserin.

The synthesis of two thiophene-containing analogues of mianserin, i.e., 1,2,3,4,10,13b-hexahydro-2-methylpiperazino[1,2-a]thieno[2, 3-c][1]benzazepine (2), and the corresponding [3,2-c] isomer (12) is described. The key step in the synthesis is the nucleophilic aromatic substitution reaction of the N-lithio derivative of 1-methyl-3-(2-thienyl)piperazine (4) with the oxazoline derivative of o-anisic acid (7) to give the N-phenylpiperazine 8. This substance was converted via ethyl ester 10 to 1-[2-(hydroxymethyl)phenyl]-4-methyl-2-(2-thienyl)piperazine (3), which was cyclized with polyphosphate ester to a 5:1 mixture of 2 and 12. The antidepressant potential of 2 maleate (CGS 11049A) and 12 fumarate (CGS 15413A) were compared with that of mianserin hydrochloride in a variety of biochemical and pharmacological test systems. The three substances exhibited generally similar profiles. However, the results suggest that 2 and 12 bind more strongly to central presynaptic alpha-receptors than does mianserin.

Animals↗

Bone marrow transplantation for acute lymphoblastic leukaemia.

Twenty patients have undergone bone marrow transplantation for acute lymphoblastic leukaemia (ALL). Eighteen patients were in complete remission and two had less than 10% leukaemic blasts in the marrow aspirate in the week prior to transplantation. Eighteen patients were grafted from HLA/MLC compatible siblings. One identical twin and one fully compatible parent were also used as donors. Two patients died of graft-versus-host disease and one of radiation-induced pneumonitis. Four have subsequently relapsed. Thirteen patients remain well and in remission from 202 to 1126 d post transplantation. These results show that morbidity and mortality from the bone marrow transplantation procedure is low. However, the major obstacle to permanent success in marrow transplantation of patients with ALL is recurrence of the disease (35% actuarial disease free survival at 1126 d).

Adolescent↗