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A Carrascosa

Publications and source records attributed to A Carrascosa.

At least 19 recordsLinked to original sources
PubMed2006

The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.

CONTEXT: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy. OBJECTIVE: The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients. DESIGN: This was a 2-yr prospective, controlled, randomized trial. SETTING: Thirty Spanish hospitals participated. Auxologic and GH secretion evaluation was hospital based, whereas molecular analyses and auxologic data computation were centralized. PATIENTS: Patients included 170 short SGA children: 140 remained prepubertal and 30 entered puberty during the second follow-up year. INTERVENTION: Eighty-six were treated with GH (66 microg/kg.d) for 2 yr and 84 were not treated. MAIN OUTCOME MEASURES: Previous and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR genotypes determined, and data analyzed for patients who remained prepubertal (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group 2). RESULTS: In group 1 GH-treated patients, growth velocity, and height-sd score during the first and second years, total 2-yr height gain (18.5 +/- 2.4 cm in d3/d3; 18.4 +/- 2.6 in d3/fl; 19.5 +/- 2.3 in fl/fl), Delta 2-yr height increase (9.1 +/- 2.4 cm in d3/d3; 9.4 +/- 3.0 in d3/fl; 10.4 +/- 2.1 in fl/fl), first-year growth prediction and studentized residual values (0.08 +/- 1.26 in d3/d3; 0.28 +/- 1.21 in d3/fl; 0.67 +/- 0.95 in fl/fl) did not differ among the d3/fl-GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor height-sd score changed significantly, and values were similar in each d3/fl-GHR genotype. Results in all patients (group 2) were similar to those in group 1. CONCLUSIONS: In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR genotype carried.

Body Height↗
PubMed2006

[Anthropometric patterns in non-Caucasian full-term neonates of African, Moroccan and South American origin born in Catalonia (Spain)].

INTRODUCTION: The rise in immigration to Spain in recent decades has increased the number of non-Caucasian newborns in our environment. The aims of this study were to establish normal intrauterine development values for weight, length and head circumference in a population of non-Caucasian full-term newborns (FTN). PATIENTS AND METHODS: We studied 2,444 healthy full-term singleton newborns (37-42 weeks' gestational age; 1,230 boys, 1,214 girls) with the following ethnic origins: black (n =1,257; 622 boys, 635 girls), Moroccan (n =520; 297 boys, 223 girls) and South-American (n =667; 356 boys, 311 girls). Mean values and standard deviations were estimated for each week of gestation for sex and race and these values were compared with those of a Spanish population of the same gestational age and sex. RESULTS: Anthropometric values in black FTN were similar to those of the Catalan population. By contrast, these values were higher in Moroccans and South-American FTN than in the native population. Statistically-significant differences were observed in all the parameters evaluated from the 38th week of gestation in full-term Moroccan newborns compared with the reference population. Statistically significant differences were observed in full-term South-American newborns from the 38th week of gestation in girls and from the 40th week in boys. The presence of sexual dimorphism in the anthropometric patterns evaluated was not constant at all the gestational ages evaluated. CONCLUSIONS: Anthropometric patterns of the Spanish Caucasian FTN population are not extrapolable to FTN of other ethnicities.

Africa↗
PubMed2004

[Anthropometric growth patterns of preterm and full-term newborns (24-42 weeks' gestational age) at the Hospital Materno-Infantil Vall d'Hebron (Barcelona)(1997-2002].

BACKGROUND AND OBJECTIVE: Gestational age and neonatal anthropometric parameters are significant predictive factors of neonatal and adult morbidity. Our objective was to evaluate these parameters in a population of preterm and full-term newborns. SUBJECTS AND METHOD: We retrospectively analyzed neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1470 live preterm neonates born at 24-36 weeks' gestation between 1997 and 2002. The same parameters were prospectively analyzed in 1786 live newborns born at 37-42 weeks after uncomplicated pregnancies between 2001 and 2002. All preterm and full-term neonates were the result of single pregnancies and were born at the Hospital Materno-Infantil Vall d'Hebron in Barcelona. Only Caucasian neonates whose parents were born in Spain were included. In the group of full-term neonates all measurements were made by the same researcher. RESULTS: The mean and standard deviation and percentile distribution values of weight, length and head circumference according to sex and gestational age are presented. These parameters progressively increased with gestational age and sexual dimorphism from the 30th week of gestation onwards, with statistically significant differences (p < 0.05) for all parameters at 38-42 weeks' gestational age. The mean gains in male full-term newborns compared with female full-term newborns were: 129.1 g of weight, 0.68 cm of length and 0.45 cm of head circumference (P < 0.05). In our population, 10th percentile values for weight and length were higher than those in other Spanish populations reported in 1988 and 1996. CONCLUSIONS: Sexual dimorphism was found in intrauterine anthropometric growth parameters. These parameters change over time and should be updated periodically.

Anthropometry↗
PubMed2004

[Pancreatectomy level in the persistent hyperinsulinic hypoglycemia].

INTRODUCTION: Persistent neonatal and infantile hyperinsulinemic hypoglycemia (PNHH) is a rare entity which remains to be elucidated but associated with severe lesions in pediatric patients. The aim of this study is to present our current surgical strategy face to this disease, based on our pathology findings and clinical experience. MATERIAL AND METHODS: It is a retrospective study of 29 patients treated at our centre, medically and surgically. In 15 surgical patients, morphologic, morphometric and immunohistochemical studies for insulin, somatostatin and glucagon were performed and consequently it has been possible to establish a focal and different forms of a diffuse type. RESULTS: Out of 29 patients studied, 25 were diagnosed before their first year old and 4 patients between the first and second infancy. Of the 25 first patients, one died at 7 hours postpartum. Twelve patients only received medical treatment, one of them died at 45 days of life and the remaining 11 patients had good outcome. Another 12 patients received in addition surgical treatment. In 2 of them we observed adenoma which was removed and patients cured. In the remaining 10 patients a subtotal pancreatectomy was performed. (One case was informed as normal and cured and the other 9 had the diffuse type). Of these 9 patients with diffuse type, 4 died, 3 cured and 2 underwent second surgery. Out of the 4 patients diagnosed in infancy, 3 underwent surgery (2 adenomas and 1 diffuse type) and the other one received only medical treatment. CONCLUSIONS: Currently, we give medical treatment in all types and forms of PNHH. If the patient is resistant, we dismiss adenoma. If this is diagnosis we remove it. If the type is diffuse, near-total pancreatectomy is performed with a peroperatory biopsy. In cases of hyperplasia or mixed form we recommend a total pancreatectomy and in case of nesidioblastosis we recommend a partial pancreatectomy.

Child↗
PubMed2002

Pancreatectomy extension in persistent hyperinsulinaemic hypoglycaemia: a new strategy.

INTRODUCTION: Persistent neonatal and infantile hyperinsulinaemic hypoglycaemia (PNHH) is a rare entity which remains to be elucidated but is associated with severe lesions in paediatric patients. The aim of this study was to present our current surgical strategy with this disease, based on our pathologic findings and clinical experience. MATERIALS AND METHODS: This is a retrospective study of 29 patients treated, medically and surgically, at our centre. In 15 surgical patients, morphologic, morphometric and immunohistochemical studies for insulin, somatostatin and glucagon were performed and consequently it was possible to establish a focal and different forms of a diffuse type. RESULTS: Of 29 patients studied, 25 were diagnosed before one year of age and 4 between the first and second year of infancy. Of the first 25 patients, one died 7 hours post partum. Twelve patients received medical treatment alone: one died at 45 days of life and the remaining 11 had a good outcome. Another 12 patients additionally received surgical treatment. In 2 of these, adenoma were observed and removed and the patients cured. Subtotal pancreatectomy was performed in the remaining 10. (One case was normal and cured and the other 9 had the diffuse type.) Of these 9 patients with diffuse type, 4 died, 3 were cured and 2 underwent repeat surgery. Of the 4 patients diagnosed later, 3 underwent surgery (2 with adenomas and 1 diffuse type) and the other received medical treatment alone. CONCLUSIONS: We currently give medical treatment for all types and forms of PNHH. If the patient is resistant to therapy, adenoma is ruled out. If adenoma is diagnosed, it is removed. If the type is diffuse, near-total pancreatectomy is performed with a perioperative biopsy. In cases of hyperplasia or mixed forms we recommend total pancreatectomy and in cases of nesidioblastosis, partial pancreatectomy.

Adenoma, Islet Cell↗
PubMed2002

Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth.

Most children born small for gestational age (SGA) experience extensive catch-up growth during the first months of life (87%) and by the age of 2 years only 13% are below -2 SDS for height. The long-term outcome, including pubertal growth spurt, of the subset of children born SGA without postnatal catch-up (SGAWPC) has been evaluated in very few surveys, and in none of them was the landmarks of puberty well described. Thus, a longitudinal study was conducted in these children throughout puberty since this is the only reliable way to accurately evaluate the pubertal growth spurt. In an observational, retrospective and multicenter collaborative study, from an initial group of 553 SGA children, a subset of 15 boys (BW = 2,070 +/- 379.6 g) and 16 girls (BW = 2,244 +/- 331.1 g) SGAWPC whose data were recorded regularly during puberty were selected. Growth standards for growth and maturity during puberty were Tanner and Whitehouse and Spanish Hernandez and Sobradillo charts. In pubertal growth spurt, 'take-off' occurred later than in the reference populations with a height SDS deficiency of -2.3 and -2.2 for boys and -2.0 and -1.9 for girls, compared with Spanish and Tanner references, respectively. Peak height velocity was normal in chronology and intensity, but the total pubertal gain was smaller. However, considering their growth from the same chronological age at which the reference populations took off until adulthood, the total gain was not significantly different in the three cohorts (32.5 +/- 5.4 cm vs 30.9 +/- 4.4 in boys, and 23.3 +/- 4.1 vs 25.7 +/- 5.4 cm in girls - Spanish reference - and 27.2 +/- 6.3 vs 27.6 +/- 3.5 cm in boys - Tanner charts), except in the case of girls (21.1 +/- 3.9 vs 25.3 +/- 4.1 cm, p <0.005 - Tanner charts). Adult height was significantly reduced (161.9 +/- 3.9 cm in males and 147.0 +/- 2.6 cm in females). Therefore, although the pubertal growth was smaller in these children, puberty probably did not modify their short final height.

Adolescent↗
PubMed2001

Growth hormone/insulin-like growth factors axis in children undergoing cardiac surgery.

OBJECTIVES: To describe the sequential changes in the growth hormone (GH)/insulin-like growth factors axis and their relationship with nitrogen balance in children following cardiac surgery. DESIGN: Prospective, descriptive study. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: Twenty three postoperative cardiac surgical patients after bypass. INTERVENTIONS: Blood and urine samples were taken on days 1, 2, and 7 of pediatric intensive care unit admission. An intraanesthesia, presurgery sample was also obtained. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of insulin, insulin growth factor-I (IGF-I), insulin growth factor binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), growth hormone binding protein (GHBP), and urinary concentrations of GH and free cortisol (UFC) were measured on days 1, 2, and 7 of the study period. C-reactive protein and prealbumin, were also measured in blood samples as conventional markers of inflammatory or nutritional status. Pediatric Risk of Mortality II score and UFC were used as indicators of acute stress. The nitrogen balance and urinary nitrogen urea excretion were used as markers of catabolic state. Urinary concentrations of GH were high from days 1 to 7. Plasma concentrations of IGF-I and GHBP were low and remained low throughout the study period. IGFBP-3 levels were below normal but without reaching statistical significance. The IGFBP-1 levels were initially high but descended progressively toward normal values. Urinary nitrogen urea production was persistently elevated and was associated with a negative nitrogen balance. No relationship was found between nitrogen balance and IGF-I, prealbumin, or C-reactive protein. CONCLUSIONS: A GH-resistant state is observed in postoperative children following cardiac surgery. Stress response is characterized by an elevation of growth hormone secretion that is not followed by the corresponding increment in IGF-I and IGFBP-3 concentrations. These hormonal changes may be permissive for the catabolic state of these patients. IGF-I and IGFBP-1 and -3 are not related to either nitrogen balance or urinary nitrogen urea excretion.

Analysis of Variance↗
PubMed2001

Hyperinsulinemia in pre- and post-pubertal children born small for gestational age.

BACKGROUND: Reduced fetal growth is a potential risk factor for development of metabolic abnormalities in later life. The relationship between low birthweight and impaired glucose tolerance, type 2 diabetes and insulin resistance in adulthood has been well documented. PURPOSE: Assuming that fetal undernutrition is associated with insulin resistance in middle age, we elected to study whether this process may already be present in young adults and adolescents born small for gestational age (SGA). SUBJECTS AND METHODS: Children born in Vall d'Hebron Hospital Infantil, Barcelona, between 1986 and 1989 and between 1978 and 1983 with birthweights below the third centile for the local standard values, were invited to participate in the present study. Of those, 51 (22 girls and 29 boys) were pre-pubertal with 9.4 +/- 0.2 years of age and 49 (29 girls and 20 boys ) were post-pubertal, with 17.3 +/- 0.3 years of age. All patients underwent a standard, 2-hour oral glucose tolerance test. Insulin and glucose responses were compared with our previously published data in control children with normal birthweight. RESULTS: The insulin response at 30 min after glucose load was significantly higher (p < 0.001) in pre- and post-pubertal girls and boys formerly SGA than in controls. In addition, the girls also had a higher insulin response at 60 and 120 min. Mean serum insulin (MSI), the area under the insulin curve during the glucose challenge, was statistically increased in pre- and post-pubertal boys and girls born SGA when compared to controls. CONCLUSION: The presence of high insulin levels after an oral glucose challenge in children and adolescents born SGA might be considered as an early marker of subsequent insulin resistance in adulthood. Furthermore, our population offers the opportunity to study the natural course of hyperinsulinemia and its outcome. Follow-up of this cohort may be helpful in distinguishing a subset of young children and adolescents in whom therapeutic intervention could be done.

Adolescent↗
PubMed2000

Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients.

Type A insulin resistance syndrome is characterized by the association of ovarian hyperandrogenism, acanthosis nigricans, and severe insulin resistance. We have identified three novel mutant alleles of the insulin receptor gene in 3 patients with type A syndrome, a severe form of insulin resistance. Two of the patients were sisters (A1, A2), 1 of them was a compound heterozygote for a mutation at the 3'-splice acceptor site of intron 21 (AG-->AA), and a missense mutation Val140Leu in exon 2. Her sister was a simple heterozygote for the 3'-splice acceptor mutation. The third patient (A3) was heterozygous for the missense mutation Ala1028Val in exon 17, in the consensus sequence for ATP binding.

Adolescent↗
PubMed2000

Low areal bone mineral density values in adolescents and young adult turner syndrome patients increase after long-term transdermal estradiol therapy.

OBJECTIVE: To study the effects of long-term estradiol therapy on areal bone mineral density (aBMD) values in young adult Turner syndrome patients. METHODS: The effects of 2-year transdermal estradiol administration on lumbar, L2-L4, aBMD values were evaluated in 12 Turner syndrome patients, 15.41-21.85 years old, who had reached adult height and had low aBMD values. Puberty was induced in all at a chronological age above 12 years and menarche appeared between 13.82 and 15.40 years. The patients were on oral estrogen/gestagen therapy from then until the start of the study. Adhesive patches of 17-beta-estradiol designed to be worn for 72 h and deliver 100 microg of estradiol per day, which results in a steady mean serum estradiol level of 75 pg/ml, were used for 21 days. From day 11 to day 21, 10 mg of oral didrogesterone were also added. Nutritional and physical activity habits were evaluated at the beginning, after 1 year and at the end of the study. RESULTS: aBMD values significantly increased from 0.910 +/- 0.065 to 1.005 +/- 0.086 g/cm2 (10.06 +/- 3.37%) and the z-score from -2.38 +/- 0.63 to -1.54 +/- 0.71 (0.81 +/- 0.30 z-score). No significant differences were observed in body mass index, calcium intake and physical activity habits at the start, during and at the end of the study. CONCLUSION: In summary, our results underline the importance of estrogens for bone mass peaking and suggest that this therapeutic protocol may be useful in the therapy of Turner syndrome patients with low bone mass.

Adolescent↗
PubMed2000

Spontaneous, but not induced, puberty permits adequate bone mass acquisition in adolescent Turner syndrome patients.

Lumbar L2-L4 bone mineral density (BMD) values were measured in 37 adolescent and young adult Turner syndrome patients. Nine had developed spontaneous puberty and had had regular menses since menarche (12.55 years +/- 1.17 years) to the time of BMD evaluation (14.96 years +/- 1.26 years). In the other 28, puberty was induced with increasing doses of oral ethinyl estradiol (2.5-10.0 microg/day, for 2 years) and later administration of estrogen/gestagen therapy up to the time of BMD evaluation. In 18, the adolescent group, menarche appeared at 14.68 years +/- 0.63 years and BMD was evaluated at 17.77 years +/- 0.70 years, and in the other 10, the young adult group, menarche appeared at 14.47 years +/- 0.53 years and BMD was evaluated at 20.90 years +/- 0.68 year. BMD values were in the normal range in those who had developed spontaneous puberty (Z score values, -0.24 +/- 0.22) and in the osteopenia range in those in whom puberty was induced (Z score values, -2.09 +/- 0.79 and -2.18 +/- 0.32 for the adolescent and young adult groups, respectively) p < 0.0001. Height Z score values were similar in all three groups (-3.45 +/- 0.77, -3.15 +/- 0.83, and -3.08 +/- 0.33, respectively). No significant differences in calcium intake or physical activity were found among groups. Neither the karyotype distribution nor growth hormone (GH) therapy (five in the spontaneous puberty and six in the induced puberty groups had been treated for a 3.5- to 4.4-year period) explained the differences in BMD values. Because the main difference between groups was the availability of estrogens to bone tissue from infancy to menarche and of estrogens/gestagens from then on up to the time of BMD evaluation, our results suggest that normal gonadal function from infancy to adulthood may be required for adequate bone mass peaking. Early detection of osteopenia and improvement in general measures for adequate bone mass peaking (calcium intake and physical activity) should be considered mandatory in the health care of these patients.

Absorptiometry, Photon↗
PubMed2000

Vascular endothelial growth factor is expressed in human fetal growth cartilage.

Angiogenesis is a crucial event in endochondral ossification. Chemoattractants and mitogens for endothelial cells (such as basic fibroblast growth factor [bFGF] and transforming growth factor beta [TGF-beta]), which act as local regulators of the process, are synthesized by chondrocytes under several stimuli and in relation to the differentiation stage of the cartilage. Vascular endothelial growth factor (VEGF) is a 44-kDa protein well known as a potent angiogenic molecule owing to its mitogenic and permeability-causing properties. In this work, VEGF was located by immunohistochemistry in growth plate cartilage of human fetuses (20-22 weeks old) and its expression was demonstrated by reverse-transcription polymerase chain reaction (RT-PCR). Primary culture of human fetal epiphyseal chondrocytes (HFEC) maintained VEGF expression at protein and messenger RNA (mRNA) levels and this expression was stimulated by cartilage-promoting growth factors incorporated into the culture media (rFGF-b, rTGF-beta1, and insulin-like growth factor [rFGF-b] at 50 ng/ml). The conditioned medium (CM) of HFEC stimulated the proliferation of endothelial cells, and this was partially blocked by anti-VEGF antibody. These studies showed VEGF production by chondrocytes of the epiphyseal growth cartilage and suggested a role of this factor in cartilage physiology and the angiogenic process.

Alternative Splicing↗
PubMed1999

[The effectiveness of recombinant growth hormone in height deficiency due to intrauterine growth retardation].

BACKGROUND: Intrauterine growth retardation (IUGR) is considered to be responsible for approximately 20% of short stature in adulthood. Although GH secretion is normal in the majority of cases, excellent results have been published by some authors using GH to treat children with height deficiency due to IUGR. PATIENTS AND METHODS: Thirty children with a history of IUGR with chronological ages between 2 and 7 years and height less than 2 SD were randomized in two groups for one year: a) control group, no treatment, 14 cases, and b) treatment group, 1 U/kg/week of recombinant GH, 16 cases. Growth and maturation were analysed periodically in both groups. In addition, serum levels of GH, IGF-I, IGFBP3 and GHBP were measured before and under treatment and adverse events were assessed in treatment group. RESULTS: In the treated group significant increments in growth rate, cm/year (median = 6.91 vs 9.94), improvement in height SDS (median = -2.19 vs -1.63) and positivation of growth rate (median = -0.13 vs 3.17) were observed compared with the control group. Bone age evolved parallelly to chronological age and the height age/bone age ratio increased throughout the study under GH therapy. Hormonal findings in the treated group showed a significant increase in IGF-I and IGFBP3 values. Glycaemia levels increased without exceeding upper normal levels in the treated group. CONCLUSION: GH was effective in promoting growth in this short-term study in children with height deficiency due to IUGR. Close follow-up is required to detect any adverse event, particularly those related to carbohydrate metabolism.

Age Determination by Skeleton↗
PubMed1999

Leptin values in placental cord blood of human newborns with normal intrauterine growth after 30-42 weeks of gestation.

OBJECTIVE: To evaluate leptin values in placental cord blood of newborns with normal intrauterine growth after 30-42 weeks of gestation. DESIGN: Leptin, a protein encoded by the ob gene, plays an important role in the regulation of feeding behaviour and energy balance in rodents, primates and humans. The presence of leptin in human amniotic fluid and cord blood has recently been reported in human gestations at term and the possible role of leptin in human fetal growth suggested. However, little is known of leptin synthesis during human foetal development. Thus, the aim of our work was to measure leptin (RIA, Linco Research, Inc.) in placental cord blood of human newborns at different fetal ages. PATIENTS: One hundred and twenty-six healthy newborns with normal intrauterine growth were studied. Twenty-nine were preterm (15 males and 14 females; gestational age: 30-36 weeks) and 99 were at term (49 males and 48 females; gestational age: 37-42 weeks). RESULTS: Leptin values increase progressively throughout gestation from 1.30 +/- 0.53 ng/ml at 30 weeks of gestation to 7.98 +/- 4.96 ng/ml (mean +/- SD) at term, and correlate positively with birth weight (r = 0.56, p < 0. 005, n = 126), length (r = 0.37, p < 0.005, n = 126), BMI (r = 0.57, p < 0.005, n = 126), head circumference (r = 0.37, p < 0.005, n = 126), gestational age (r = 0.48, p < 0.005, n = 126) and placental weight (r = 0.38, p < 0.003, n = 59). Leptin values are statistically significantly lower (p < 0.005) preterm (median: 2.05 ng/ml; range: 0.7-8.3 ng/ml) than at term (median: 7.0 ng/ml; range: 1.1-28.1 ng/ml). Leptin values are also significantly (p < 0.005) higher in females (median: 7.2 ng/ml; range: 0.9-23.6 ng/ml, n = 62) than in males (median: 4.8 ng/ml; range: 0.7-28.1 ng/ml, n = 64), although there are no differences in weight (2,864 +/- 536 g in females vs. 2,937 +/- 744 g in males). Multiple regression analysis shows weight to be a positive sex-independent predictor of serum leptin values (p < 0.0005). Sex also proves to be a predictor of leptin, independently of weight and is higher in females than in males (p < 0.003). CONCLUSION: Leptin is present in placental human cord blood after 30-42 weeks of gestation. Newborn weight and sex are independent predictors of leptin values.

Birth Weight↗
PubMed1999

Genetic determinants of bone mass.

A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1alpha1, TGF-beta1, interleukin-6, calcitonin receptor, alpha2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.

Animals↗
PubMed1999

Effects of TGF-beta1 on proliferation and IGFBP-3 production in a primary culture of human fetal epiphyseal chondrocytes (HFEC).

Proliferation and differentiation of chondrocytes from growth cartilage are modulated by hormones and growth factors, among which TGF-betas have been recognized as some of the more potent regulators although their specific cell effects on cartilage physiology are not fully understood. Primary human fetal epiphyseal chondrocytes (HEFC) constitutively produce TGF-beta1 at different times of culture progression. Treatment of 48-h. serum-deprived semiconfluent HFEC with 0.1-50 ng/ml of TGF-beta1 for 48-h. decreased (3H)Thymidine incorporation by 25-50 % and cell number by 25 %. In addition, IGFBP-3, the main insulin-like bonding protein produced by HFEC, showed a slight increase by TGF-beta1 in culture media. The changes in IGFBP-3 protein levels correlated well with its mRNA, indicating that TGF-beta1 is able to up-regulate IGFBP-3 synthesis in chondrocytes. Nevertheless, the IGFBP-3 accumulation in culture media does not produce a clear growth inhibitory effect on chondrocytes. Thus, we conclude that even though TGF-beta1 is able to up-regulate IGFBP-3, the growth inhibitory action produced by TGF-beta1 is not mediated by IGFBP-3 increase and appears to be mainly a direct TGF-beta1 effect on HFEC.

Cell Division↗