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Biomedical subjects

J A Yanovski

Publications and source records attributed to J A Yanovski.

At least 19 recordsLinked to original sources
PubMed2004

Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer.

Uncontrolled trials have reported significant weight gain in women with breast cancer during treatment with adjuvant chemotherapy. We prospectively evaluated body composition before (visit 1), immediately after (visit 2), and 6 months after (visit 3) chemotherapy in 20 women with stages I-IIIA breast cancer [body mass index (BMI): 24.1 +/- 3.9 kg/m(2)]. We compared their weight change to 51 age- and BMI-matched healthy controls (BMI: 25.5 +/- 3.8 kg/m(2)). In women with breast cancer, there was no weight change from visit 1-2, or from visit 1-3, but weight increased from visit 2-3 (+1.09 +/- 2.46 kg; P = 0.05). Weight change was not different from controls during either interval. In the breast cancer group, the percentage of body fat assessed by air displacement plethysmography increased, and fat-free mass decreased from visit 1-2 (+2.3 +/- 4% and -2.2 +/- 4%; P = 0.02) and from visit 1-3 (+4.0 +/- 6% and -3.8 +/- 6%; P = 0.01). By dual energy x-ray absorptiometry, the percentage of body fat increased from visit 2-3 (+0.9 +/- 1.6%; P = 0.02). Bone mineral content decreased from visit 2-3 (-0.02 +/- 0.04 kg; P = 0.02) and from visit 1-3 (-0.04 +/- 0.06 kg; P = 0.005). By computed tomography, the visceral adipose to sc adipose tissue ratio decreased from visit 1-3 (-0.02 +/- 0.05 ml; P = 0.02). We conclude that, compared with controls, women with breast cancer receiving modern adjuvant chemotherapy regimens show no significant changes in weight during the first year of their treatment. They do, however, appear to undergo unfavorable changes in body composition.

Absorptiometry, Photon↗
PubMed2003

Associations between a polymorphism in the 11 beta hydroxysteroid dehydrogenase type I gene and body composition.

We investigated 11 beta hydroxysteriod dehydrogenase type 1 (11betaHSD-1) sequence variants in 103 healthy overweight (BMI >2 s.d.) and 160 nonoverweight (BMI -2 to +2 SD) children to examine the associations between body composition and 11betaHSD-1 polymorphisms. A total of 4.3% of children were homozygous and 30.0% heterozygous for an adenine insertion in intron 3 (ins4436A). By ANCOVA (adjusting for age, sex, race, and height), BMI-s.d. differed according to ins4436A genotype (P<0.005), with the greatest BMI-SD for ins4436A homozygotes (mean +/-s.d., 3.4+/-3.4, vs heterozygotes, 0.8+/-5.5, or wild-type, 1.8+/-7.5). Homozygotes also had greater waist circumference, waist-to-hip ratio, and insulin resistance indices than heterozygote or wild-type children (all P<0.05), but no significant differences in trunk fat by DXA, or in serum lipids. We conclude an intronic 11betaHSD-1 gene polymorphism is associated with greater body mass, altered body composition, and insulin resistance in children. 11betaHSD-1 may be one of the genes relevant for pediatric-onset obesity and its complications.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

Comparison of insulin sensitivity, clearance, and secretion estimates using euglycemic and hyperglycemic clamps in children.

The euglycemic clamp is the gold standard for estimating insulin sensitivity. The hyperglycemic clamp is easier to perform and is the gold standard for estimating beta-cell secretion. Reports in adults suggest that hyperglycemic clamps can estimate insulin sensitivity with results equivalent to euglycemic clamps. We investigated whether insulin sensitivity measures from both clamps are equivalent in children. Thirty-one lean and obese children (mean body mass index, 25.1 +/- 4.9 kg/m(2); mean age, 8.7 +/- 1.4 yr; 15 girls and 16 boys; 12 black and 19 white) were studied. All subjects underwent hyperglycemic clamps, then euglycemic clamps 2-6 wk later. Body composition was estimated by dual energy x-ray absorptiometry. Visceral and sc abdominal fat was estimated by abdominal magnetic resonance imaging. Whole-body glucose disposal and insulin sensitivity (SI clamp) derived from both clamps and normalized for total or visceral fat and lean mass were significantly correlated (r, 0.45-0.65; P < 0.05). However, absolute SI clamp values were not equivalent. Bland-Altman comparisons found that SI clamp estimates from hyperglycemic clamps became less precise as SI clamp increased. There were significant correlations between indices of beta-cell secretion from the hyperglycemic clamp and mean C-peptide values from the euglycemic clamp (P < 0.05). However, no correlation was found between measures of total insulin clearance (derived from the euglycemic clamp) and surrogates of hepatic insulin clearance (derived from the hyperglycemic clamp). In this cohort of diverse children, SI clamp values from euglycemic and hyperglycemic clamps were significantly correlated but were not equivalent, whereas the insulin clearance measures were not correlated. It cannot be assumed that the hyperglycemic clamp obviates the need for euglycemic clamp studies to accurately estimate insulin sensitivity in children.

Black People↗
PubMed2001

Intensive therapies for pediatric obesity.

The intensive therapies that have been used to treat pediatric and adolescent obesity include very-low-calorie diets, pharmacotherapy, and bariatric surgery. None of these approaches have been reported in sufficient numbers of subjects who have taken part in well-designed experiments with long-term follow-up to demonstrate convincingly their true value for the treatment of pediatric obesity. As the potency of the therapy increases, so does its possible adverse consequences. Of the intensive approaches, only bariatric surgery can be said to have even small studies supporting its ability to induce long-lasting (> 1 year) effects on body weight in severely obese adolescents. The risks and benefits of intensive weight-management therapies should be weighed carefully before they are used with pediatric-aged patients. Until further controlled trials become available, intensive therapies for pediatric obesity should be considered only for children who have not responded to conventional weight-management programs but have significant complications of their obesity. Intensive approaches generally should be restricted to specialized centers that have experience with those treatments and should be carried out in the context of a comprehensive weight-management program.

Adolescent↗
PubMed2001

Pediatric obesity.

Pediatric obesity can be defined as BMI > 95th percentile for age and sex from large surveys that were carried out in the past. Using these cut points, over 10% of all children and adolescents are obese, and another 10% are overweight (BMI > 85th percentile). Obesity in childhood is associated with many immediate consequences, including orthopedic, neurologic, pulmonary, gastroenterologic, endocrinologic, metabolic, and cardiovascular disorders. Psychosocial and economic problems also are seen in obese adolescents. Long-term consequences of pediatric obesity include risks for cardiovascular disease and death that are independent of adult body weight. The differential diagnosis of pediatric obesity includes many multi-system genetic syndromes and a limited number of endocrine disorders that include abnormalities in the leptin signaling pathway, but most children with excess body weight do not have an established diagnosis. Treatment is best carried out at specialized centers, and usually involves a program of behavioral modification, caloric restriction, increased activity, and decreased sedentary behaviors. Medication for pediatric obesity cannot be recommended at present outside the context of clinical trials. Gastric bypass surgery is effective, but should be considered a last resort for the child with life-threatening complications of obesity.

Body Mass Index↗
PubMed2001

Effect of growth hormone treatment on testicular function, puberty, and adrenarche in boys with non-growth hormone-deficient short stature: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of growth hormone (GH) therapy on pubertal onset, pubertal pace, adult testicular function, and adrenarche in boys with non-GH-deficient short stature. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. GH (0.074 mg/kg, subcutaneously, 3 times per week) or placebo treatment was initiated in prepubertal or early pubertal boys and continued until near final height was reached (n = 49). Statistical significance was assessed by survival analysis, repeated-measures analysis of variance, and Student t test. RESULTS: GH therapy did not affect the age at pubertal onset, defined either by testicular volume >4 mL or by testosterone concentration >1.0 nmol/L (30 ng/dL). GH treatment also did not affect the pace of puberty, defined either by the rate of change in testicular volume or testosterone concentration during the 4 years after pubertal onset. In boys followed up to age > or =16 years during the study, there were no significant differences in final testicular volume or in plasma testosterone, luteinizing hormone, or follicle-stimulating hormone concentrations. The pace of adrenarche, assessed by change in dehydroepiandrosterone sulfate levels over time, also did not differ significantly between the GH and placebo groups. CONCLUSION: Our findings suggest that GH treatment does not cause testicular damage, alter the onset or pace of puberty, or alter the pace of adrenarche in boys with non-GH-deficient short stature.

Adolescent↗
PubMed2001

Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children.

OBJECTIVES: Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinism has not been systematically evaluated in overweight children. We examined the relationship of AN to hyperinsulinemia and body adiposity. STUDY DESIGN: One hundred thirty-nine children underwent physical examination for AN, body composition studies, an oral glucose tolerance test, and a hyperglycemic clamp. RESULTS: Thirty-five children (25%) had AN. AN was more prevalent in African Americans (50.1%) than in white subjects (8.2%, P < .001). Independent of race, children with AN had greater body weight and body fat mass (P < .001); greater basal and glucose-stimulated insulin levels during oral glucose tolerance test (P < .001); greater first-phase, second-phase, and steady-state insulin levels (P < .001); and lower insulin sensitivity (P < .001) during the hyperglycemic clamp. After adjusting for body fat mass and age, none of these differences remained significant. When categorized by fasting insulin, 35% with fasting insulin levels > 20 microU/mL and 50% with fasting insulin levels > 15 microU/mL did not have AN. Eighty-eight percent of children with fasting insulin levels > or = 15 microU/mL had a body mass index SD score > or = 3.0. CONCLUSIONS: AN is not a reliable marker for hyperinsulinemia in overweight children. Children with a race-, sex-, and age-specific body mass index SD scores > or = 3.0 should be screened for hyperinsulinemia, whether or not they have AN.

Acanthosis Nigricans↗
PubMed2001

The relation between skeletal maturation and adiposity in African American and Caucasian children.

OBJECTIVE: African American children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for by their greater adiposity. STUDY DESIGN: We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (BMI SDS), and fat mass by dual energy x-ray absorptiometry (DXA). RESULTS: African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P <.05). Both BA - CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P <.05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P <.05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SDS, and DXA fat mass (all r > 0.46, P <.001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SDS, or DXA fat mass. CONCLUSION: Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity.

Absorptiometry, Photon↗
PubMed2001

Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study.

In this study, the authors investigated the physiologic effects of the altered body composition that results from surgical removal of large amounts of subcutaneous adipose tissue. Fourteen women with body mass indexes of greater than > 27 kg/m2 underwent measurements of fasting plasma insulin, triglycerides, cholesterol, body composition by dual-energy x-ray absorptiometry (DXA), resting energy expenditure, and blood pressure before and after undergoing large-volume ultrasound-assisted liposuction. There were no significant intraoperative complications. Body weight had decreased by 5.1 kg (p < 0.0001) by 6 weeks after liposuction, with an additional 1.3-kg weight loss (p < 0.05) observed between 6 weeks and 4 months after surgery, for a total weight loss of 6.5 kg (p < 0.00006). Body mass index decreased from (mean +/- SEM) 28.8 +/- 2.3 to 26.8 +/- 1.5 kg/m2 (p < 0.0001). This change in body weight was primarily the result of decreases in body fat mass: as assessed by DXA, lean body mass did not change (43.8 +/- 3.1 kg to 43.4 +/- 3.6 kg, p = 0.80), whereas DXA total body fat mass decreased from 35.7 +/- 6.3 to 30.1 +/- 6.5 kg (p < 0.0001). There were significant decreases in fasting plasma insulin levels (14.9 +/- 6.5 mIU/ml before liposuction versus 7.2 +/- 3.2 mIU/ml 4 months after liposuction, p < 0.007), and systolic blood pressure (132.1 +/- 7.2 versus 120.5 +/- 7.8 mmHg, p < 0.0002). Total cholesterol, high-density lipoprotein cholesterol, plasma triglycerides, and resting energy expenditure values were not significantly altered after liposuction. In conclusion, over a 4-month period, large-volume liposuction decreased weight, body fat mass, systolic blood pressure, and fasting insulin levels without detrimental effects on lean body mass, bone mass, resting energy expenditure, or lipid profiles. Should these improvements be maintained over time, liposuction may prove to be a valuable tool for reducing the comorbid conditions associated with obesity.

Absorptiometry, Photon↗
PubMed2001

Estimation of body fatness by air displacement plethysmography in African American and white children.

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal African American and white children. One hundred nineteen nonoverweight and overweight boys (N = 56) and girls (N = 63), age (mean +/- SD) 9.8 +/- 1.7 y, body mass index 25.9 +/- 7.6 kg/m2 (range, 14.2-47.0 kg/m2), and mean percent body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 +/- 11.7% (range, 12.2-57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and with body fat by several field methods: skinfold thicknesses using the Slaughter et al. equations (Hum Biol 60: 709-723, 1988), bioelectrical impedance analysis (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366-373, 1992), and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et al.: Am J Clin Nutr 63: 299-305, 1996). All methods used to estimate %BF were significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85 (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated %BF by -1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as +/-2 SD) were +/-7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP and DXA did not vary with age, race, or pubertal stage. Application of the age-adjusted Lohman model to ADP significantly increased the magnitude of the underestimation to -6.9% (p < 0.0001). Prediction of %BF by the Slaughter skinfold thickness equation showed no significant mean bias for the overall data, but significantly underestimated %BF in girls (-3.7%) while overestimating %BF in boys (+2.4%) with wide limits of agreement (+/-17.7%, p < 0.01 versus ADP). %BF by the Houtkooper BIA equation or Goran model underestimated %BF to a significantly greater degree than ADP (Houtkooper, -8.1%; Goran, -10.1%; both p < 0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model slightly underestimates %BF as determined by DXA in girls, but appears to be superior to existing field methods both in accuracy and limits of agreement. Because of the ease with which it can be performed, ADP may prove useful for investigations of adiposity in children.

Adipose Tissue↗
PubMed2001

Relationships between walk/run performance and cardiorespiratory fitness in adolescents who are overweight.

BACKGROUND AND PURPOSE: Little is known about the methods used to assess the physical fitness of adolescents who are overweight. We investigated the relationship between walk/run performance and cardiorespiratory fitness in adolescents who are overweight. SUBJECTS: Eight African-American adolescents (5 female, 3 male) and 10 Caucasian adolescents (5 female, 5 male) who were overweight (mean age=14.5 years, SD=2.0, range=12-17; mean body mass index [BMI]=42.9 kg/m2, SD=11.5) participated in this study. METHODS: Subjects performed a 12-minute walk/run test. The distances traveled at both 9 minutes (D9) and 12 minutes (D12) were recorded, and the distance traveled between 9 and 12 minutes (D9-12) was calculated. Subjects also completed a maximal cycle ergometry test, during which peak oxygen uptake (VO2peak), anaerobic threshold (AT), peak power (Wpeak), and power at the anaerobic threshold (WAT) were determined. Body composition was determined by air displacement plethysmography. RESULTS: The mean percentage of body fat was 48.6% (SD=5.3%, range=40.3%-60.4%). Percentage of body fat and BMI were each inversely related to D9, D12, and VO2peak (all P<.005). Peak oxygen uptake (r=.72, P=.0001), VO2peak/kg lean body mass (r=.60, P<.005), Wpeak (r=.88, P<.0001), and WAT (r=.72, P=.0007) were all related to D12, with greater r values than for D9. If D9-12was included in regression analyses, D9 did not account for additional variance in any of the cycle ergometry variables. DISCUSSION AND CONCLUSION: These results suggest that an easily obtained measurement of physical performance (distance traveled during a 12-minute walk/run test) is related to cardiorespiratory fitness and to body composition in adolescents who are overweight. The 12-minute walk/run distance is more predictive of cycle ergometry test results than the 9-minute distance.

Adolescent↗
PubMed2000

Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy.

BACKGROUND: HAART has been associated with metabolic abnormalities (hyperlipidemia, insulin resistance, alterations in cortisol metabolism) and fat redistribution. SETTING: A prospective study of 26 Caucasian men (median age 43.5 years) with HIV-1 viral loads < 500 copies/ml for 12 months while on highly active antiretroviral therapy (HAART) who interrupted treatment for a median of 7.0 weeks (range 4.9-10.3 weeks). Seventeen (65.4%) patients reported at least one fat redistribution symptom at baseline. METHOD: Serum lipids, glucose and insulin levels during an oral glucose tolerance test, 24-h urinary free cortisol and 17-hydroxycorticosteroids, and anthropometric parameters were measured before HAART cessation and prior to its reinstitution. RESULTS: When baseline values were compared with those obtained after HAART interruption (means +/- SD), there was a significant decrease in total cholesterol (194+/-47.3 versus 159+/-29.3 mg/dl; P < 0.0001), low density lipoprotein (LDL) cholesterol (114+/-32.6 versus 96+/-24.7 mg/dl; P = 0.0013), triglycerides (261+/-244.3 versus 185+/-165.4 mg/dl; P = 0.008), and 24-hour urinary 17-hydroxycorticosteroids (15+/-7.9 versus 5+/-2.5 mg/24 h, P < 0.0001) and a significant increase in 24-hour urinary free cortisol (45+/-34.1 versus 62+/-32.2 microg/24 h; P = 0.016). There were no significant changes in glucose or insulin levels or in anthropometric measurements. CONCLUSIONS: A relatively brief interruption of HAART resulted in significant improvements in total cholesterol, LDL cholesterol, and triglyceride levels. No changes were observed in insulin resistance profiles or anthropometric measurements, perhaps because of the brief duration of HAART interruption. These results suggest that hyperlipidemia and alterations in corticosteroid metabolism in the setting of HAART are a direct drug effect that reverses with drug withdrawal. However, glucose metabolism and fat redistribution do not change over the short term.

Adult↗
PubMed2000

A prospective study of holiday weight gain.

BACKGROUND: It is commonly asserted that the average American gains 5 lb (2.3 kg) or more over the holiday period between Thanksgiving and New Year's Day, yet few data support this statement. METHODS: To estimate actual holiday-related weight variation, we measured body weight in a convenience sample of 195 adults. The subjects were weighed four times at intervals of six to eight weeks, so that weight change was determined for three periods: preholiday (from late September or early October to mid-November), holiday (from mid-November to early or mid-January), and postholiday (from early or mid-January to late February or early March). A final measurement of body weight was obtained in 165 subjects the following September or October. Data on other vital signs and self-reported health measures were obtained from the patients in order to mask the main outcome of interest. RESULTS: The mean (+/-SD) weight increased significantly during the holiday period (gain, 0.37+/-1.52 kg; P<0.001), but not during the preholiday period (gain, 0.18+/-1.49 kg; P=0.09) or the postholiday period (loss, 0.07+/-1.14 kg; P=0.36). As compared with their weight in late September or early October, the study subjects had an average net weight gain of 0.48+/-2.22 kg in late February or March (P=0.003). Between February or March and the next September or early October, there was no significant additional change in weight (gain, 0.21 kg+/-2.3 kg; P=0.13) for the 165 participants who returned for follow-up. CONCLUSIONS: The average holiday weight gain is less than commonly asserted. Since this gain is not reversed during the spring or summer months, the net 0.48-kg weight gain in the fall and winter probably contributes to the increase in body weight that frequently occurs during adulthood.

Adult↗
PubMed2000

Insulin-like growth factors and bone mineral density in African American and White girls.

OBJECTIVES: African American children have greater bone mineral density (BMD) and bone mineral content (BMC) than white children. We examined the hypothesis that differences in insulin-like growth factors (IGFs) are important determinants of BMD during childhood. METHODS: We measured IGFs and IGF binding proteins in 59 African American and 59 white girls matched for age, body mass index, socioeconomic status, and pubertal stage. BMD and BMC were determined by dual emission x-ray absorptiometry. RESULTS: African American girls had greater total BMD (P <.001), BMC (P <.01), total IGF-1 (P <.001), and free IGF-1 (P <.01) than white girls. IGFBP-1, IGFBP-2, and IGFBP-3 were similar in both groups or lower in African Americans. IGF-1 was positively correlated with IGF-2 in white girls (P =.012) but was negatively correlated with IGF-2 in African Americans (P =.015). IGF-1 and free IGF-1 were positively correlated with BMD/BMC. Multiple regression analyses showed 80% of the variance in BMC could be accounted for by the use of body weight, height, and IGF-1 in the model. When IGF-1 was included as a factor, race did not add to the model's predictive power. CONCLUSION: IGF-1 and free IGF-1 are greater in African American than in white girls and may contribute to the greater BMD of African Americans.

Black People↗
PubMed2000

Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children.

BACKGROUND: Little is known about genes that affect childhood body weight. OBJECTIVE: The objective of this study was to examine the association between alleles of the mitochondrial uncoupling protein 2 (UCP2) gene and obesity because UCP2 may influence energy expenditure. DESIGN: We related UCP2 genotype to body composition and resting energy expenditure in 105 children aged 6-10 y. Overweight children and nonoverweight children of overweight parents were genotyped for a 45-base pair deletion/insertion (del/ins) in 3'-untranslated region of exon 8 and for an exon 4 C to T transition. RESULTS: Eighty-nine children were genotyped for the exon 8 allele: 50 children had del/del, 33 had del/ins, and 6 had ins/ins. Mean (+/-SD) body mass index (BMI; in kg/m(2)) was greater for children with del/ins (24.1 +/- 5.9) than for children with del/del (20.4 +/- 4.8; P < 0.001). BMI of ins/ins children (23.7 +/- 7.8) was not significantly different from that of del/ins children. A greater BMI in del/ins children was independent of race and sex. Body composition was also different according to UCP2 genotype. All body circumferences and skinfold thicknesses examined were significantly greater in del/ins than in del/del children. Body fat mass as determined by dual-energy X-ray absorptiometry was also greater in del/ins than in del/del children (P < 0.005). For 104 children genotyped at exon 4, no significant differences in BMI or body composition were found among the 3 exon 4 genotypes. Neither resting energy expenditure nor respiratory quotient were different according to UCP2 exon 4 or exon 8 genotype. CONCLUSIONS: The exon 8 ins/del polymorphism of UCP2 appears to be associated with childhood-onset obesity. The UCP2/UCP3 genetic locus may play a role in childhood body weight.

Asian People↗
PubMed2000

Retinoic acid is a potent regulator of growth plate chondrogenesis.

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.

Alkaline Phosphatase↗