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Biomedical subjects

A M Sharma

Publications and source records attributed to A M Sharma.

At least 73 records · Page 4Linked to original sources
PubMed2000

Kinetic analysis of the thermic effect of food and its relationship to body composition in humans.

The course of energy expenditure after a meal can vary widely with regard to the slope of onset, amplitude, and duration of the thermic effect. The aim of the present study was to explore the relationship between the thermic effect of food (TEF), as characterized by kinetic analysis of postprandial energy expenditure, body composition, and variables related to the metabolic syndrome including central obesity, hypertension, and glucose tolerance. A total of 181 men and women (body mass index [BMI] range, 19.4 to 52.2 kg/m2) were characterized for body composition, blood pressure, oral glucose tolerance, and energy expenditure after a test meal. Energy expenditure, as measured by indirect calorimetry, was analyzed over a 6-hour period by 3-parameter curve fitting using equations derived from kinetics describing a biphasic reaction involving 2 consecutive first-order reactions (A-->B-->C). Apart from total thermic effect of food (TEFk), the curve also provided an estimate of time of peak (Tp) and amplitude of peak (Ap) for each subject. Multiple stepwise regression analysis with TEFk, Ap, and Tp as dependent variables showed significant effects of sex, age, body weight, body fat, beta-blockade, and body composition on TEF curve parameters. Cluster analysis based on Tp shown 2 distinct clusters with significant differences in age and body fat mass. This study shows that kinetic analysis of postprandial energy expenditure can be used to examine the determinants of the time course of the thermic effect of food in man.

Adult↗
PubMed2000

G-protein beta(3)-subunit C825T genotype and nephropathy in diabetes mellitus.

BACKGROUND: Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta(3) subunit of heterotrimeric G proteins (G:beta(3)) which is associated with enhanced activation of G-proteins and appears to be more common in hypertensive patients and possibly contributes to decreased kidney allograft survival. METHODS: In the present study we examined the relationship between this genetic variant, type 1 and type 2 diabetes and renal complications of diabetes in 1008 Caucasian patients recruited from an outpatient diabetes clinic and four dialysis centres. We also studied 1940 healthy controls. RESULTS: After multivariate adjustment and in univariate statistics, the G:beta(3) 825TT genotype was not associated with a significantly enhanced risk of diabetes or renal complications. CONCLUSIONS: These findings indicate that the G:beta(3) 825T allele apparently does not contribute to the development of diabetes or associated renal complications in patients with type 1 or type 2 diabetes mellitus.

Adult↗
PubMed2000

G-protein beta3 subunit 825T allele and response to dietary salt in normotensive men.

BACKGROUND AND AIMS: A functional single-nucleotide variant of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3 C825T), associated with enhanced G-protein activation and increased activity of the sodium-proton exchanger (NHE1), has been implicated in the development of hypertension. Given the possible involvement of NHE1 in sodium homeostasis, we tested the hypothesis that the Gbeta3 825T allele determines the response of the renin-angiotensin system and blood pressure to dietary salt restriction. METHODS: Young normotensive men (20-30 years old, n = 193) were recruited within the framework of the Berlin Salt-Sensitivity Trial and studied on low- (20 mmol/day) and high-salt (220 mmol/day) dietary protocols. Subjects were characterized for parameters of the renin-angiotensin system and blood pressure response and genotyped for the Gbeta3 C825T polymorphism. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium (CC = 90, CT = 81 and TT = 22). The responses of the renin-angiotensin system and blood pressure to the dietary protocol were virtually identical between the genotypic groups. Furthermore, when subjects were classified as salt-resistant (n = 145) or salt-sensitive (n = 48), genotype distribution was comparable between the two groups (salt-resistant: TT = 17, CT = 60, CC = 68, qT = 0.32; salt-sensitive: TT = 5, CT = 21, CC = 22, qT = 0.32). CONCLUSION: These findings do not support the hypothesis that the Gbeta3 C825T polymorphism determines the response of the renin-angiotensin system to salt depletion or can serve as an early genetic marker of salt sensitivity in young normotensive men.

Adult↗
PubMed2000

Physiology and pathophysiology of the adipose tissue renin-angiotensin system.

The renin-angiotensin system has long been recognized as an important regulator of systemic blood pressure and renal electrolyte homeostasis, and local renin-angiotensin systems have also been implicated in pathological changes of organ structure and function by modulation of gene expression, growth, fibrosis, and inflammatory response. Recently, substantial data have been accumulated in support of the notion that adipose tissue, besides other endocrine functions, also hosts a local renin-angiotensin system. In the first part of this review, we describe the components of the adipose tissue renin-angiotensin system in human and rodent animal models with respect to regulation of angiotensinogen expression and secretion, formation of angiotensin peptides, and the existence of angiotensin II receptors. In the second part, we describe the role of the adipose tissue renin-angiotensin system in the process of adipogenic differentiation and in the regulation of body weight. We also detail the differential regulation of the adipose tissue renin-angiotensin system in obesity and hypertension and thereby also speculate on its possible role in the development of obesity-associated hypertension. Although some findings on the adipose tissue renin-angiotensin system appear to be confusing, its involvement in the physiology and pathophysiology of adipose tissue has been confirmed by several functional studies. Nevertheless, future studies with more carefully described phenotypes are necessary to conclude whether obesity (by stimulation of adipogenic differentiation) and hypertension are associated with changes of renin-angiotensin system activity in adipose tissue. If so, the physiological relevance of this system in animal models and humans may warrant further interest.

Adipose Tissue↗
PubMed2000

Resting metabolic rate and substrate use in obesity hypertension.

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.

Adult↗
PubMed2000

Salt intake and hypertension in renal transplant patients.

BACKGROUND: Dietary salt restriction is currently widely recommended as an important non-pharmacological measure for the treatment of hypertension. However, the relationship between dietary salt intake and post-transplant hypertension has not been extensively investigated. PATIENTS AND METHODS: We examined the relationship between dietary salt intake and the prevalence of hypertension in 129 renal transplant patients with stable allograft function (serum creatinine < 400 micromol/l, variation in serum creatinine during the preceding two months < 20%). Salt intake was assessed by measuring 24-hour urinary excretion of sodium on an unrestricted diet. Hypertension was defined based on the prescription of antihypertensive medication, and the number of antihypertensive drugs was considered a surrogate marker for severity of hypertension. Patients were divided into tertiles based on urinary sodium excretion and analyzed by chi2-testing. RESULTS: The prevalence of hypertension was 74% and the mean sodium excretion was 178 mmol/d (range: 56 to 603). There was no statistical difference in the frequency of antihypertensive medication between patients with low (76%, UNa = 107 mmol/d), medium (73%, UNa = 178 mmol/d), or high sodium (73%, UNa = 272 mmol/d) excretion. Furthermore, the number of antihypertensive drugs (in treated patients) was similar between the tertiles. There was also no correlation between urinary sodium excretion and systolic (r = -0.05) or diastolic (r = 0.08) blood pressure levels. CONCLUSION: We conclude that dietary salt intake in transplant patients with stable allograft function is higher than currently recommended. There is, however, no relationship between salt intake and the prevalence of hypertension in these patients. These data do not support the hypothesis that the prevalence or severity of post-transplant hypertension is markedly affected by dietary salt intake.

Humans↗
PubMed1999

Pro12Ala missense mutation of the peroxisome proliferator activated receptor gamma and diabetes mellitus.

Peroxisome proliferator activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates adipocyte differentiation and possibly lipid metabolism and insulin sensitivity. Therefore, PPARgamma is a promising candidate gene for several disorders including diabetes, obesity, and dyslipoproteinemia. Screening for mutations in the entire coding region of the PPARgamma gene yielded a missense C --> G mutation at codon 12, resulting in the substitution of proline with alanine (Pro12Ala). The objective of our study was to examine the relationship between this genetic variant and diabetes and associated diseases in a large group of patients with type 1 (n = 522) and type 2 (n = 503) diabetes. Allelic frequencies of the PPARgamma2 12Ala allele were similar between patients with either type of diabetes and comparable to that in healthy controls (n = 310). There was also no significant relationship between dyslipoproteinemia or obesity and the PPARgamma2 Pro12Ala genotype. Thus, our data, in this large and ethnically homogenous group of patients, do not support the hypothesis that this genetic variant is strongly associated with diabetes, obesity, or dyslipidemia in patients with type 1 or type 2 diabetes mellitus. This genetic marker is therefore unlikely to serve as a clinically useful predictor of these disorders in Caucasian patients with diabetes mellitus.

Adult↗
PubMed1999

Monitoring dialysis efficacy by comparing delivered and predicted Kt/V.

INTRODUCTION: In Europe, especially in Germany, little is currently known about the relationship between delivered and predicted haemodialysis doses for patients on maintenance haemodialysis. We compared delivered and predicted Kt/V in patients of an outpatient dialysis centre in Berlin by calculating the ratio of delivered and predicted Kt/V, resulting in the efficacy quotient, QE. Moreover, we studied the influence of technical and anthropometric parameters on both delivered Kt/V and QE under routine clinical conditions. METHODS: Blood samples were taken after the long interval in a thrice-weekly regimen before and 10 min after ultrafiltration and 100 ml/min slow-pump method. Delivered Kt/V was computed using the Daugirdas III formula. Predicted Kt/V was estimated from the dialysis filter urea clearance given by the manufacturer, treatment time and the total body water (V) computed by the Watson formula and was corrected for real blood flow. As and when appropriate, bivariate and multivariate regression analyses were used to make comparisons. RESULTS: The mean quotient (QE) between delivered and predicted Kt/V was 1.02+/-0.20. Mean delivered Kt/V in 377 treatments of 128 patients was 1.28+/-0.27. Delivered Kt/V and QE were positively associated (P<0.001). QE was significantly associated with post-HD urea, body mass index (BMI) and sex, but not with session time. Significant positive predictors for delivered Kt/V were post-dialysis urea, sex, session time, blood flow and kind of vascular access. BMI was inversely related to delivered Kt/V. DISCUSSION: In this study, the relationship between delivered and predicted Kt/V (QE) was reproducible and close to the ideal value of 1.0. In contrast to delivered Kt/V, QE was not influenced by session time, and positively by BMI. Since QE gives a valid measure of technical dialysis efficacy we suggest the use of this parameter in addition to delivered Kt/V to monitor HD adequacy in clinical routine more comprehensively.

Body Mass Index↗
PubMed1999

Neurogenic hypertension. A new MRI protocol for the evaluation of neurovascular compression of the cranial nerves IX and X root-entry zone.

OBJECTIVE: Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been implicated in the pathogenesis of essential hypertension. Although MRI has been widely used to evaluate the morphologic relation of structures in this region, spatial resolution of the previously used techniques was limited. This article describes the use of a new MRI protocol that combines two sequences with improved spatial resolution and complementary image information as well as a set of defined criteria for image analysis. METHODS: MRI of the brain stem was performed in 60 hypertensive and 50 normotensive subjects using a 3D-CISS and a 3D-FISP-MRA sequence. Neurovascular contact in the RVLM was independently assessed by four readers using predefined criteria and compared with a consensus finding. Agreement was expressed by kappa statistics on a 0 to 1 scale. RESULTS: Left-sided neurovascular contact within the RVLM was found in 13 (22%) hypertensive and 6 (12%) control subjects. The inter-reader agreement for positive and negative findings ranged from 0.47 to 0.79; agreement to the consensus finding ranged from 0.65 to 0.90. CONCLUSIONS: The combination of 3D-CISS and arterial flow-sensitive 3D-FISP, together with the evaluation criteria defined in this study, can be used for describing the finer anatomic features of the brain stem, and in particular for investigation of neurovascular contact of the IX/X cranial nerve root-entry zone. The high quality of images and the substantial or almost perfect reader-consensus agreement should make this protocol useful for future investigations of the neurovascular compression syndrome in patients with essential hypertension and possibly in other neurovascular compression syndromes, such as trigeminal neuralgia and hemifacial spasm.

Adult↗
PubMed1999

Angiotensinogen M235T variant and salt sensitivity in young normotensive Caucasians.

BACKGROUND AND AIMS: A single-nucleotide variant of the angiotensinogen gene (AGT 235T) has been associated with essential hypertension and increased plasma levels of angiotensinogen. This variant may also serve as a genetic marker for the increased blood pressure response to dietary salt intake, but the relationship between AGT genotype and salt sensitivity has not been studied until now. We therefore examined the relationship between the AGT 235T genotype and the blood pressure response to short-term dietary salt restriction in young normotensive men. SUBJECTS AND METHODS: A total of 187 young normotensive men were characterized for family history of hypertension, salt sensitivity, plasma parameters of the renin-angiotensin system under high- and low-salt diets, and the AGT 235T genotype. RESULTS: While the T allele was significantly associated with a positive family history of hypertension (chi2 = 7.0; P< 0.03) and higher plasma angiotensinogen levels (P< 0.015) and renin activity (P < 0.037), blood pressure under both diets was not significantly affected by the AGT genotype. When the subjects were classified into salt-resistant and salt-sensitive groups, genotypic distribution was nearly identical between both groups (frequency of T allele: 0.45 versus 0.46). CONCLUSION: Our findings demonstrate that the AGT 235T allele is significantly associated with a positive family history of hypertension, but is not an important determinant of the blood pressure response to dietary salt intake in young normotensive subjects. It is therefore unlikely that the AGT 235T genotype can serve as an early genetic marker of salt sensitivity.

Adult↗
PubMed1999

Co-expression of renin-angiotensin system genes in human adipose tissue.

OBJECTIVE: The renin-angiotensin system plays a central role in blood pressure regulation, both by affecting renal function and by modulating vascular tone and structure. Recent studies in rodents demonstrated the existence of several components of this system in adipose tissue. The activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in obesity-associated hypertension. Few data are available on the presence of renin-angiotensin system components in human adipose tissue. MATERIALS AND METHODS: In order to explore the expression of renin-angiotensin system genes in human adipose tissue and adipocytes, total RNA was isolated from whole adipose tissue (subcutaneous and omental) or cultured adipocytes (mammary) and subjected to reverse-transcriptase polymerase chain reaction with primers specific for human angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors. RESULTS: Angiotensinogen, angiotensin converting enzyme and type 1 angiotensin receptor genes were widely expressed, both in human adipose tissue and in cultured human adipocytes. Furthermore, we found expression of the chymase and renin-binding protein genes in these samples. CONCLUSIONS: Our findings suggest the presence of a local renin -angiotensin system in human adipose tissue, with adipocytes being an important part of this system, and prompt speculation that this local renin-angiotensin system may be involved in obesity-related disorders, including hypertension and the metabolic syndrome.

Adipose Tissue↗
PubMed1999

Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST).

OBJECTIVE: Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, the T allele of a polymorphism in the 5'-flanking region of the CYP11B2 gene (C-344T) has been reported to be more frequent in hypertensives than in normotensives, and has also been associated with increased plasma aldosterone levels. We therefore hypothesized that this variant may be related to increased blood-pressure response to dietary salt intake. SUBJECTS AND METHODS: We genotyped 1 63 young normotensive men recruited within the framework of the Berlin Salt-Sensitivity Trial (BeSST) for the CYP11B2 C-344T polymorphism. Subjects were characterized for family history of hypertension, plasma parameters of the renin-angiotensin-aldosterone system and blood-pressure response to a high (220 mmol/day) and low (20 mmol/day) salt diet RESULTS: The frequency of the -344T allele (0.45) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (CC, n = 55; CT, n = 71; TT, n = 37). There was a trend towards a higher frequency of the T allele in subjects with a positive family history of hypertension (0.48 versus 0.42), but the C-344T genotype was not related to blood pressure under either diet Furthermore, when subjects were classified into salt-sensitive and salt-resistant groups, allelic distribution did not differ between the two groups (qT = 0.43 versus qT = 0.45). While renin activity and plasma aldosterone levels were not related to genotype, plasma angiotensinogen was significantly higher in T-allele carriers under both the high (P = 0.02) and low (P = 0.008) salt diet. CONCLUSION: Our findings do not support the hypothesis that the C-344T polymorphism of the CYP11B2 gene is associated with salt sensitivity or increased activity of the renin-angiotensin system in young normotensive subjects. It is, therefore, unlikely that the C-344T polymorphism is a genetic marker for salt sensitivity in young normotensive Caucasian men.

Adult↗
PubMed1999

G-Protein beta3 subunit C825T variant and ambulatory blood pressure in essential hypertension.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3) associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study we examine the relationship between this genetic variant and hypertension in 479 white patients with established essential hypertension recruited from the hypertension clinic of the Universitätsklinikum Benjamin Franklin in Berlin, Germany, and 1000 normotensive gender- and age-matched controls. All patients were screened for the presence of secondary hypertension and were further characterized by ambulatory blood pressure measurements performed in 295 treated and 184 untreated patients. Genotype distribution for the Gbeta3-C825T genotype in patients (CC=204, CT=224, TT=51) was significantly different from that in controls (CC=514, CT=412, TT=74; chi2=11.5, P<0.01), and the T allele was associated with an odds ratio of 1.5 (95% CI, 1.1 to 2.2) versus non-T carriers for the presence of hypertension. However, in both the whole group and the untreated subgroup, blood pressure levels between the genotypic groups were virtually identical. Furthermore, age of onset of hypertension and number of antihypertensive medications (in treated patients) were similar between the genotypic groups. Thus, while our data confirm the association between the Gbeta3-C825T variant and essential hypertension, they do not support the hypothesis that this marker is associated with more severe blood pressure in patients with already established hypertension.

Adult↗
PubMed1999

Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2.

Salt-sensitive subjects (SS) increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, we hypothesize that the activity of the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme is impaired in SS subjects as compared with salt-resistant (SR) subjects. The 11betaHSD2 enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. We performed an association study using a recently identified single AluI polymorphism in exon 3 and a polymorphic microsatellite marker of the HSD11B2 gene in 149 normotensive white males (37 SS and 112 SR). The activity of the enzyme 11betaHSD2 was assessed by determining the urinary ratio of cortisol (THF+5alphaTHF) to cortisone (THE) metabolites by gas chromatography in all the 37 SS subjects and in 37 age- and body habitus-matched SR volunteers. Mean (THF+5alphaTHF)/THE ratio was markedly elevated in SS subjects compared with SR subjects (1.51 +/- 0.34 vs. 1.08 +/- 0.26, P < 0.00001), indicating enhanced access of glucocorticoids to the mineralocorticoid receptor in SS subjects. In 58% of SS subjects this ratio was higher than the maximum levels in SR subjects. The salt-induced elevation in arterial pressure increased with increasing (THF+5alphaTHF)/THE ratio (r2 = 0.51, P < 0.0001). A total of 12 alleles of the polymorphic microsatellite marker were detected. Homozygosity for the allele A7 was higher in SS subjects than in SR subjects (41 vs. 28%, P < 0.005), whereas the occurrence of the allele A7 with allele A8 was lower in SS subjects than in SR subjects (8 vs. 15%, P < 0.03). The prevalence of salt sensitivity was 35% in subjects with allele A7/A7, whereas salt sensitivity was present in only 9% of the subjects with allele A7/A8. The (THF+5alphaTHF)/THE ratio was higher in subjects homozygous for the A7 microsatellite allele as compared with the corresponding control subjects. The prevalence of the AluI allele was 8.0% in SR subjects and 5.4% in SS subjects and did not correlate with blood pressure. The decreased activity of the 11betaHSD2 in SS subjects indicates that this enzyme is involved in salt-sensitive blood pressure response in humans. The association of a polymorphic microsatellite marker of the gene with a reduced 11betaHSD2 activity suggests that variants of the HSD 11B2 gene contribute to enhanced blood pressure response to salt in humans.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.

Adult↗