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Biomedical subjects

N Kumar

Publications and source records attributed to N Kumar.

At least 199 records · Page 11Linked to original sources
PubMed1995

Feedback regulation of gonadotropins by androgens in rats: is 5 alpha-reduction involved?

The action of testosterone (T) on the sex accessory organs, such as ventral prostate (VP) and seminal vesicles (SV) is amplified by its 5 alpha-reduction to dihydrotestosterone (DHT). This does not happen in the case of muscle (levator ani, LA) which contains little or no 5 alpha-reductase activity. It has been suggested that the regulation of gonadotropins by T may also be mediated by its 5 alpha-reduced metabolites. We investigated this question by utilizing two types of androgens: (1) T and 17 alpha-methyl-testosterone (17MT), whose potency increases following 5 alpha-reduction; and (2) 19-nortestosterone (NT) and 17 alpha-methyl-19-nortestosterone (17MNT) whose potency decreases following 5 alpha-reduction. Castrated rats were used to investigate the ability of these androgens to stimulate VP, and SV (androgenic action) and LA growth (anabolic action) and to suppress the post-castration rise in LH levels. In addition, modification of these actions by a 5 alpha-reductase inhibitor (5 alpha-RI) was studied. Compared to T, NT was approximately 5 times less potent in stimulating VP and SV. By contrast, it was twice as potent as T in stimulating LA growth. Similarly, 17MNT was 5 times less androgenic but twice as anabolic as 17MT. The antigonadotropic potency of both the 19-nor compounds was 2-3 times greater than that of their respective 19-methylated parent compounds. The similarity in their anabolic and antigonadotropic potency suggested that 5 alpha-reduction is not a factor in their antigonadotropic action. This was confirmed by the use of the 5 alpha-RI. Treatment of rats receiving the androgens with 5 alpha-RI showed that it decreases the androgenic activity of T and 17MT while it increases the androgenic activity of NT and 17 MNT. In all cases the anabolic activity and the antigonadotropic potency remained unchanged. It is concluded that the regulation of pituitary gonadotropin secretion by T does not depend upon its 5 alpha-reduction to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens.

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5 alpha-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5 alpha-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5 alpha-reduction of the steroids does not occur in the muscle. 7 alpha-methyl-19-nortestosterone (MENT) does not get 5 alpha-reduced due to steric hindrance from the 7 alpha-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7 alpha-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.

Anabolic Agents↗
PubMed1995

Aortic valve replacement with freehand autologous pericardium.

Fifty-one patients with a mean age of 31.2 years underwent aortic valve replacement with glutaraldehyde-treated autologous pericardium. Pure aortic regurgitation was present in 28 (54.9%), stenosis in 9, and mixed disease in 14. Simultaneous mitral valve repair was done in 17 patients and replacement in 1. There were no hospital and two late deaths. Three patients required reoperation because of failure of the pericardial valve as a result of infective endocarditis in two (5 and 31 months after operation) and commissural tear at 8 months in another. One patient underwent reoperation at 24 months because of failure of the mitral valve repair. The pericardial aortic valve, which had 2+ regurgitation since the first operation, was also replaced. Macroscopic and microscopic examination findings in the excised pericardium were excellent. No thromboembolic events have been detected and no patient received anticoagulation therapy except one after mitral valve reoperation and replacement with a mechanical valve. The actuarial survival was 84.53% +/- 12.29% at 60 months, freedom from failure of the aortic reconstruction 83.83% +/- 8.59%, and freedom from any event 72.59% +/- 12.79%. Doppler echocardiographic study at most recent follow-up showed a mean gradient of 12.56 +/- 8.10 mm Hg and mean regurgitation on a scale from 0 to 4+ of 0.80 +/- 0.66. Although the maximum follow-up is only 5 years, the results obtained so far encourage us to continue replacing the aortic valve with stentless autologous pericardium.

Adolescent↗
PubMed1995

Photoinstability of some tyrphostin drugs: chemical consequences of crystallinity.

PURPOSE: The purpose of this work was to study the photostability of the antiproliferative tyrphostin drug compounds RG 13022(I) and RG 14620(II) as a part of preformulation program. METHODS: The compounds were exposed to cool white fluorescent light in solution as well as in the solid state and analyzed by HPLC. The degradation products were isolated chromatographically and their structures determined by spectroscopic methods. X-ray crystallographic analyses of the above compounds and their solid state degradation products were carried out to understand the mechanism of photodegradation. RESULTS: The compounds were found to undergo efficient photochemical transformations in solution as well as in the solid state. The degradation in the solution was due to the photoisomerization into their E-isomers (III and IV). The solid state photodegradation products were [2 + 2]-cycloaddition products (V and VI). The stereochemistry of the photocycloaddition products was indicative of the crystal packing of their monomeric precursors. The photocycloaddition product of RG 13022 possesses the head-to-tail linkage as expected from the head-to-tail packing of RG 13022 molecules in the crystal. The photocycloaddition product of RG 14620, however, was found to involve head-to-head linkage in agreement with the head-to-head crystal packing of RG 14620. CONCLUSIONS: Drug compounds containing open chain olefinic double bonds could be sensitive to mild condition of light in the solid state if the distance between the two double bonds in the crystal approaches 4.2 degrees A and they have suitable UV absorption characteristics. Attractive interactions between chlorine atoms have significant influence in controlling the crystal packing of chlorinated aromatic compounds.

Alkenes↗
PubMed1995

Antagonism of mivacurium block with edrophonium from various degrees of spontaneous recovery.

Seventy adult patients received mivacurium 0.15 mg kg-1 during anaesthesia with thiopentone, nitrous oxide and 0.5% halothane. Neuromuscular block was monitored using mechanomyography and train-of-four stimulation. Edrophonium 0.75 mg kg-1 was administered 5 or 10 min after mivacurium, or when the first response in the TOF (T1) had recovered to 5, 10, 25 or 50% of control in groups of 10 patients each. A control group was allowed to recover spontaneously. The mean time taken from administration of mivacurium to attaining a TOF ratio of 0.7 was between 19.3 and 24.9 min in the groups given edrophonium, regardless of the time of administration, compared with 26.7 min in the spontaneous recovery group. The differences, however, were not significant among the groups showing little advantage in antagonizing mivacurium block.

Adult↗
PubMed1995

Aortic valve replacement with autologous pericardium: surgical technique.

The surgical technique of aortic valve replacement with freehand glutaraldehyde-treated autologous pericardium is described. Forty-nine patients underwent this procedure without hospital mortality and no thromboembolic episodes without anticoagulation. Three patients underwent reoperation: for infective endocarditis in two; and tear of one commissure 8 months after surgery in another. This technique because of its excellent hemodynamics and low thrombogenicity might be a valid alternative particularly in patients with a small aortic annulus.

Adolescent↗
PubMed1995

Comparison of fresh and glutaraldehyde-treated autologous stented pericardium as pulmonary valve replacement.

The use of fresh autologous pericardium in valve surgery has shown poor results in the past mainly due to thickening and retraction. Recently, it has been suggested that a short treatment with glutaraldehyde might radically change its behavior. In an attempt to determine whether this disparity in results is due to the glutaraldehyde treatment or to a better present-day surgical technique, fresh and glutaraldehyde-treated autologous pericardium was mounted in a frame and implanted in the pulmonary position of adult sheep. Six survivors obtained in each group were sacrificed between 2 and 8 months in the "fresh" group and between 2 and 6 months in the "glutaraldehyde-treated" group. Macroscopically, the fresh pericardium became thickened and retracted in all specimens, eventually resulting in severe regurgitation, while the glutaraldehyde-treated, although slightly thickened, retained its pliability without significant retraction. Microscopically, viability of the central core of the collagen was more often preserved in the fresh pericardium. Endothelialization was irregular. In conclusion, short glutaraldehyde treatment seems to improve the results of autologous pericardium mounted on a valve stent. Its effect on calcification remains to be ascertained.

Animals↗
PubMed1995

Transmission blockade of Plasmodium falciparum malaria by anti-Pfs230-specific antibodies is isotype dependent.

By use of the parental hybridoma cell line 63F2A2 that produces specific antibodies of immunoglobulin isotype G1 (IgG1; 63F2A2.1) against Pfs230, we attempted to enrich for the synthesis of the downstream switch variant IgG2b and IgG2a monoclonal antibodies (MAbs) of the hybridoma cell line (63F2A2.2b and 63F2A2.2a, respectively). The parental IgG1 did not reduce the Plasmodium falciparum transmission in a bioassay irrespective of the presence of complement. MAbs 63F2A2.2b and 63F2A2.2a were effective in reducing the infectivity of P. falciparum parasites to Anopheles gambiae mosquitoes in membrane-feeding experiments. A transmission reduction of 91% was accomplished by the 63F2A2.2b switch variant, and a reduction of greater than 99% was accomplished by the 63F2A2.2a switch variant, but only in the presence of active human complement. Subsequently, the transmission-reducing effect of MAb 63F2A2.2b or 63F2A2.2a was confirmed in vitro by the rapid lysis of newly formed macrogametes or zygotes in the presence of active complement. MAb 63F2A2.1 did not lyse the newly formed macrogametes or zygotes irrespective of the presence of complement.

Animals↗
PubMed1995

Mechanism of androgen-induced thymolysis in rats.

To investigate the mechanism of androgen-induced thymolysis, the effects of various androgens, including testosterone (T), 19-nortestosterone, and 7 alpha-methyl-19-nortestosterone (MENT), were compared with those of estradiol and dexamethasone (DEX) in intact, castrated, and adrenalectomized male rats. The potency comparisons on thymus regression, based on mass of steroids, showed DEX to be the most potent, followed by estradiol and the androgens. Among the androgens, MENT was the most potent, followed by nortestosterone and T, an order similar to their anabolic potency on muscle. As the thymolytic effects of T and MENT were not altered by the concomitant administration of an aromatase inhibitor or a 5-reductase inhibitor, it was concluded that the effects of androgens were not mediated by their conversion to estrogens or 5 alpha-reduced metabolites. Involvement of glucocorticoid receptors in androgen action was excluded because mifepristone (an antiglucocorticoid) blocked DEX-induced, but not T- or MENT-induced, thymus regression. Flutamide, an antiandrogen, significantly blocked the thymolytic effect of T and MENT, providing further support for this conclusion. This suggested that the thymolytic action of androgens is an intrinsic property mediated via androgen receptors (AR). The occurrence of AR in the thymus was demonstrated by binding assays and the presence of AR messenger RNA (mRNA) by reverse transcriptase-polymerase chain reaction. Quantitative reverse transcriptase-polymerase chain reaction for AR mRNA in the thymus showed 6-fold more AR mRNA in the thymic epithelial cells than in the thymocytes. However, epithelial cells represent only a small fraction of the thymus. Hence, it is hypothesized that the androgens produce their thymolytic effects by stimulating the secretion of a factor(s) by the thymic epithelial cells that, in turn, causes regression of the thymus.

Adrenalectomy↗
PubMed1995

A revised terminology for recording surgical findings of the mitral valve.

The existing terminology for the various structures of the mitral valve are diverse and numerous. With the resurgence of interest in reparative procedures for mitral valve disease, it becomes imperative to have a unified terminology which would convey precise connotations in recording the pathology as well as the corrective procedures applied. In an effort to suggest a commonly acceptable nomenclature, we reviewed the available terminology and propose a simple system which will fulfil the needs of recording the intraoperative observations of the pathology of each valve and the manouveres carried out to correct them by the surgeon. This involves designating all structures anterior to the intercommissural line as "anterior" or "A" and those posterior as "posterior" or "P". The structures, as observed by the surgeon through a standard left atriotomy, to the left of the line dropped perpendicular to the middle of the aortic curtain will be designated by the numeral "1" and those to the right "2". The chords will be termed in groups based on their point of insertion, irrespective of whether they are inserted to the free edge or the ventricular surface of the leaflet. The anterior leaflet chords will further be subdivided based on their relation to the stay chords. We hope that this system of naming the structures would provide a unified method of reporting intraoperative findings of mitral valve disease.

Heart Valve Diseases↗
PubMed1995

Understanding the factors behind the decision to purchase varying coverage amounts of long-term care insurance.

OBJECTIVE: This article examines the factors related to an individual's decision to purchase a given amount of long-term care insurance coverage. DATA SOURCE AND STUDY SETTING: Primary data analyses were conducted on an estimation sample of 6,545 individuals who had purchased long-term care (LTC) insurance policies in late 1990 and early 1991, and 1,248 individuals who had been approached by agents but chose not to buy such insurance. Companies contributing the two samples represented 45 percent of total sales during the study year. STUDY DESIGN: A two-stage logit-OLS (ordinary least squares) choice-based sampling model was used to examine the relationship between the expected value of purchased coverage and explanatory variables that included: demographic traits, attitudes, risk premium, nursing home bed supply, and Medicaid program configurations. DATA COLLECTION: Mail surveys were used to collect information about individuals' reasons for purchase, attitudes about long-term care, and demographic characteristics. Through an identification code, information on the policy designs chosen by these individuals was linked to each of the returned mail surveys. The response rate to the survey was about 60 percent. PRINCIPAL FINDINGS: The model explains about 47 percent of the variance in the dependent variable-expected value of policy coverage. Important variables negatively associated with the dependent variable include advancing age, being married, and having less than a college education. Variables positively related include being male, having more income, and having increasing expected LTC costs. Medicaid program configuration also influences the level of benefits purchased: state reimbursement rates and the presence of comprehensive estate recovery programs are both positively related to the expected value of purchased benefits. Finally, as the difference between the premium charged and the actuarially fair premium increases, individuals buy less coverage. CONCLUSIONS: An important finding with implications for policymakers is that changes in Medicaid policy affect the decisions of consumers regarding the acquisition of private LTC policies as well as the level of protection chosen. This is particularly important to states interested in pursuing public-private partnerships in long-term care financing.

Actuarial Analysis↗
PubMed1995

Ring enhancing CT lesions--a diagnostic dilemma.

We studied 68 such cases of RECTL with follow up ranging from 3 months to 3 years. Patients were divided into 3 groups depending on the size of ring ie. Group I (less than 5 mm), Group II (5-10 mm), Group III (10-20 mm). Maximum cases were in Group II (42), in the age group 20-40 years. 60 cases presented with seizures. Single ring was seen in 46 cases and multiple rings in remaining 22 cases. There were 22 cases of tuberculoma, 15 neurocysticercosis, 15 disappearing lesions, 4 malignancy, 2 abscess, 1 each showing infarction and gliosis and 8 of unknown etiology. Partial or total excision biopsy was done in 18 cases of which 3 were due to tuberculoma, 7 neurocysticercosis, 4 tumours, 2 abscess and 1 each due to infarction and gliosis. We found that RECTL could be a real diagnostic problem, which could be solved only be repeated clinical examination and CT Scan with excision biopsy in some selected cases.

Diagnosis, Differential↗