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Biomedical subjects

S K Singh

Publications and source records attributed to S K Singh.

At least 19 recordsLinked to original sources

Inhibition of hog liver folylpolyglutamate synthetase by 5-substituted 5,8-dideaza analogues of folic acid bearing a terminal L-ornithine residue.

Five new N alpha-(5,8-dideazapteroyl)-L-ornithines have been prepared using multistep synthetic sequences. These include N alpha-[5-(trifluoromethyl)-5,8-dideazapteroyl]-L-ornithine, 3, as well as N alpha-[5-(trifluoromethyl)-5,8-dideazaisopteroyl]-L-ornithine, 4, and its 5-fluoro and 5-chloro analogues. Both of the compounds containing a 5-(trifluoromethyl) group (3 and 4) were found to be excellent inhibitors of homogeneous hog liver folylpolyglutamate synthetase, having Ki values in the same range as N alpha-(5-chloro-5,8-dideazapteroyl)-L-ornithine, 2, (approximately 10 nM). However, the bridge-reversed isomer of 2 was 60-fold less inhibitory than 2.

Animals

Synthesis and biological evaluation of N alpha-(5-deaza-5,6,7,8-tetrahydropteroyl)-L-ornithine.

A novel folic acid analogue, N alpha-(5-deaza-5,6,7,8-tetrahydropteroyl)-L-ornithine, 3, was prepared via a multistep synthetic sequence. The key steps involved the conversion of 5-deazapteroic acid to its N10-formyl derivative followed by catalytic hydrogenation of the pyridine ring and subsequent heating in dilute sodium hydroxide to afford the new 5-deaza-5,6,7,8-tetrahydropteroic acid. After trifluoroacetylation, this compound was coupled to N delta-(tert-butyl-oxycarbonyl)-L-ornithine using conventional peptide bond forming conditions. Deprotection first in base and then in acid gave the title compound. Compound 3 was an effective inhibitor of hog liver folylpolyglutamate synthetase (Kis, estimated = 64 nM), and was shown to retard the formation of polyglutamates of a structurally related folic acid analogue in HCT-8 cells in vitro.

Adenocarcinoma

Tuberculous pyomyositis in a renal transplant recipient.

Infections are a major cause of morbidity and mortality in renal transplant recipients. Although these patients are susceptible to many types of infection, soft tissue infections are rare. We report a case of tuberculous pyomyositis involving the left erector spinae muscle but with no other manifestations of tuberculosis. The diagnosis was suspected from the CT scan appearance and confirmed by microscopy and culture of the pus. Surgical incision and drainage, together with antituberculosis therapy, cured the infection. The relevant literature is briefly reviewed.

Adult

Degree of asymmetry in lateral preferences: eye, foot, ear.

Lateral asymmetry in eye, foot, and ear preference was measured using a 15-item questionnaire administered to 442 subjects. Degree and magnitude of asymmetry were greatest for eye, followed by foot and ear. Intercorrelations of lateral preferences were all positive and significant. Two primary factors, eyedness and earedness, were established.

Adult

Giant calculus in anterior urethral diverticulum.

The case of probably the largest stone in a giant anterior urethral diverticulum presenting with septicemia and renal failure is reported. Stage surgical reconstruction had an excellent result.

Diverticulum

Kala-azar in Ballia district, Uttar Pradesh.

Door to door search during 1991 in 85 villages in Ballia district of Uttar Pradesh revealed 29 sporadic cases of Kala-azar in four villages. Epidemiological investigations indicated indigenous transmission in Phulwaria village (PHC: Dubhar) with 25 cases while the remaining three villages showed four imported cases from the endemic states. No kala-azar cases had been reported in Ballia between 1947 and the present investigation. Phlebotomus arqentipes, the known vector of kala-azar in India, was encountered in 10 PHCs including the four villages having kala-azar cases. Regular vigilance in Ballia and the neighbouring districts in Uttar Pradesh bordering Bihar is suggested in view of indigenous transmission detected in one village with multiple infection in families. The presence of high vector density, ambient environmental factors and absence of regular residual insecticidal spray warrant constant surveillance in Kala-Azar prone areas in Uttar Pradesh.

Adolescent

Isolated invasive candidal prostatitis.

Fungal prostatitis is an uncommon entity. Herein we report a case of isolated candidal prostatitis in an elderly patient who presented with acute urinary retention and was clinically diagnosed as having benign hypertrophy of the prostate. Histology of the resected prostate demonstrated invasive prostatic involvement by Candida albicans. There was no evidence of systemic involvement by Candida. The relevant literature and treatment of isolated Candidal prostatitis have been highlighted.

Aged

Effect of fenfluramine on serum T3, T4 and TSH levels in obesity.

A prospective, randomised case-control trial of an anorectic drug, fenfluramine was conducted on 30 patients of simple obesity. The study revealed that the drug was well tolerated, non-toxic and effective in reducing the body weight and normalising the thyroid profile. Reduction in body weight, rise in serum thyroxine (T4) and fall in serum triiodothyronine (T3) was highly significant (p less than 0.01) in drug treated group as compared to controls (p less than 0.05) after 12 weeks of therapy. There was also fall in serum thyroid stimulating hormone (TSH) levels but without any statistical significance.

Adult

Immuno-modulation by exercise: review.

Chronic and exhaustive exercise leads to a decline in mitogen-induced lymphocyte proliferation in-vitro and in-vivo. This is suggestive of decrease in cellular and humoral immunity. Majority of workers are of opinion that exercise-induced immunosuppression is related to the production of glucocorticoids in response to the stress associated with exercise.

Adult

Does the Kaufman prosthesis still have a place? Review of thirteen years' experience.

The cases of 57 patients who underwent implantation of a Kaufman prosthesis for urinary incontinence at this center are reviewed. All except one of the patients were incontinent following prostatic surgery. Although many of the patients required revision or adjustments after the initial implantation, 55 percent of the cases eventually had a satisfactory outcome. Patients rendered incontinent after retropubic prostatectomy had a higher success rate with the Kaufman prosthesis than patients after other types of prostatectomy. This simple and relatively inexpensive device can still play a useful role in the treatment of patients with mild and moderate stress incontinence following prostatectomy.

Aged

Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues.

Prompted by recent disclosures concerning the potent antitumor activities of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8-tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4- oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9-CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also synthesized. Each of the new analogues was evaluated with a variety of folate-requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of ca. 1 microM against MCF-7 cells and was nearly 100-fold less potent than DDATHF in this regard. The three oxidized isofolate analogues were all poor inhibitors of tumor cell growth.

Animals

Growth hormone response to clonidine in obese children.

Basal and stimulated serum growth hormone (GH) levels after exercise, insulin induced hypoglycemia (IIH) and oral clonidine were evaluated in 20 (16 M, 4 F) normal statured obese (body mass index greater than or equal to 25 kg/M2) children. Basal serum GH levels (mean +/- SEM, 2.0 +/- 0.38 ng/ml) were not different from basal levels in non-obese children. The mean peak levels were 3.16 +/- 1.17 ng/ml, 2.15 +/- 0.36 ng/ml and 3.15 +/- 1.12 ng/ml (+/- SEM) after exercise, IIH and oral clonidine, respectively. The positive responses (peak level of serum GH greater than 7 ng/ml) were seen in 10% with exercise, in 10% with clonidine and in none with IIH test. These observations suggest that GH response to oral clonidine is subnormal in obese children.

Adolescent

Ethanol potentiates in vivo hepatotoxicity of endosulfan in adult male rats.

In an attempt to evaluate the effect and interaction of ethanol on endosulfan-induced hepatotoxicity in vivo to adult male rats, both, endosulfan (7.5 mg/kg body wt) and ethanol (1.5 g/kg body wt) were studied separately as well as in combination after a chronic oral exposure of 30 days. When fed separately, both the agents were found to induce microsomal mixed function oxidase (MFO) system in treated animals. A simultaneous induction in the activity of cytosolic GSH-s-transferase was found to be associated with significantly induced ascorbate-induced microsomal lipid peroxidation. Both endosulfan and ethanol showed increasing trends in the activities of reducing equivalent (NADPH)-generating enzymes in liver. The activity of hepatic alcohol dehydrogenase was, however, found to be relatively unaffected. When ethanol was administered in combination with endosulfan, the observed effects on the activities of major drug metabolizing enzymes, microsomal lipid peroxidation and NADPH generation were further pronounced. Findings demonstrated the MFO inducing capability of both endosulfan and ethanol, and showed further that chronic ethanol ingestion might potentiate the in vivo hepatotoxicity of endosulfan if administered in combination.

Animals

Multiple mechanisms of ethanol-induced gonadal toxicity to adult male rats.

In an attempt to elucidate the mechanism(s) underlying the alcohol-induced pathogenesis of testis, acute as well as chronic studies were undertaken in adult male rats. Ethanol reduced significantly the plasma and testicular testosterone contents in treated rats even at moderate dose levels. The alterations in pituitary gonadotrophins, LH and FSH, demonstrated a central defect in the hypothalamo-hypophyseal-gonadal axis. Major microsomal enzymes involved in the biosynthesis of testosterone, viz. 3 beta-hydroxysteroid dehydrogenase and steroidogenic mixed function oxidases were markedly inhibited in a dose and duration dependent manner. The terminal enzyme 17 beta-hydroxysteroid dehydrogenase was, however, unaffected by ethanol treatments except at a higher dose level of 6 g/kg body wt. Although, the activity of testicular alcohol dehydrogenase was relatively unchanged, a marked induction in the activity of cytosolic conjugation enzyme, GSH-s-transferase was noticed. The present study demonstrates the major role of the metabolism of ethanol in the underlying cause for in vivo toxicity of ethanol and warrants its further consideration.

Animals