Bone mineral density in young women of the city of Säo Paulo, Brazil: correlation with both collagen type I alpha 1 gene polymorphism and clinical aspects

Osteoporosis is a multifactorial disease with great impact on morbidity and mortality mainly in postmenopausal women. Although it is recognized that factors related to life-style and habits may influence bone mass formation leading to greater or lower bone mass, more than 85 percent of the variation in bone mineral density (BMD) is genetically determined. The collagen type I alpha 1 (COLIA1) gene is a possible risk factor for osteoporosis. We studied a population of 220 young women from the city of Säo Paulo, Brazil, with respect to BMD and its correlation with both COLIA1 genotype and clinical aspects. The distribution of COLIA1 genotype SS, Ss and ss in the population studied was 73.6, 24.1 and 2.3 percent, respectively. No association between these genotypes and femoral or lumbar spine BMD was detected. There was a positive association between lumbar spine BMD and weight (P<0.0001), height (P<0.0156), and body mass index (BMI) (P<0.0156), and a negative association with age at menarche (P<0.0026). There was also a positive association between femoral BMD and weight (P<0.0001), height (P<0.0001), and BMI (P<0.0001), and a negative correlation with family history for osteoporosis (P<0.041). There was no association between the presence of allele s and reduced BMD. We conclude that a family history of osteoporosis and age at menarche are factors that may influence bone mass in our population

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 + 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 + 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 + 6.6 years (mean+SD). Analysis of VDR gene polymorphism by restriction fragment lenght polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5 percent BB, 42.5 percent and 37 percent bb did not differ significantly from the values obtained for group II (16 percent BB, 36 percent Bb and 48 percent bb) or for group III (10.2 percent BB, 47.6 percent Bb and 41.8 percent bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurence of osteoporotic fractures with advancing age.

Calcitonina monomérica plasmática e hipercalcemia em pacientes portadores de neoplasia pulmonar / Monomeric plasmatic calcitonin and hypercalcemia in lung cancer patients

A calcitonina (CT) é um hormonio peptídico relacionado ao metabolismo de calcio produzido pelas células C da tiróide. Encontra-se com níveis plasmaticos bastante elevados no carcinoma medular de tiróide e mostra-se como excelente marcador dessa doença. No entanto, existem relatos na literatura que demonstraram níveis elevados deste peptídio em pacientes portadores de outras neoplasias, principalmente no carcinoma de pulmao. Objetivo. Avaliar a validade da dosagem da CT sérica como possível marcador tumoral em pacientes portadores de tumor de pulmao de diferentes tipos histológicos. Métodos. Foram dosados CT plasmatica e calcio ionizado sanguíneo em 56 pacientes portadores de tumores malignos de pulmao. Para as dosagens de CT os autores utilizaram um método de radioimunoensaio específico, realizado após extraçao prévia do soro em coluna de sílica. Resultados. Observou-se prevalência de hipercalcemia de 21,4 por cento; apenas três (5,4 por cento) dos 56 pacientes investigados apresentaram níveis pouco elevados de calcitonina, e o restante manteve níveis normais ou identectaveis do peptídio. Conclusao. Os resultados demonstram que, com a utilizaçao de um método bastante específico para dosagem da calcitonina em sua forma monomérica, nao se encontram níveis elevados deste hormonio em pacientes portadores de neoplasia pulmonar, desestimulando sua utilizaçao como marcador tumoral nesta patologia.

Monoclonal antibodies specific for the free alpha subunit of glycoprotein hormones and their use in the development of a sensitive immunofluorometric assay

Glicoprotein hormone free alpha subunit has been used as a marker for some pituitary tumors and to study the reactivity of glycoprotein hormone-producing cells under different circunstances. We describe a highly sensitive ans specific immunofluorometric assau for the measurement of serum free alpha subunit levels. The assay is based on a monoclonal antibody, specific for free alpha subunit, bound to microtiter plates. As tracer antibody we employed an europium-labelled free/complexed alpha subunit specific monoclonal antibody. Using overnight incubation and 50µl samples, the least detectable dose was of the order of 4 ng/1. Cross-reactivity with LH, TSH, FSH, and hCG was 6.5, 1.2, 4.3 and 1.1 percent, repectively. Normal adult males showed values ranging from 120 to 790ng/l, not different from normal adult premenopausal females (88 to 604 ng/l). In post-menopausal females, serum concentrations were significantly highler, ranging from 341 to 407 ng/l. In 56 patients with untreated pituitary tumors (18 "non-secreting", 25 GH-producing and 13 prolactin-producing tumors), 10 showed high values, 3 of them from the first group, 3 from the second and 4 from the third. We conclude that this highly sensitive assay can be a valualbe tool for the diagnosis and follow-up of selected patients with pituatary tumors and in other circumstances in which the glycoprotein hormone-producing cells of the pituitary require evaluation

Development and clinical application of an immunoflurometric assay for intact parathyroid hormone

Parathyroid hormone (PTH) is a linear peptide of 84 amino acids that is found in serum mainly in the form of carboxyl-terminal fragments. The biological activity of PTH depends on the presence of the amino-terminal portion and in circulation is limited to the intact molecule. We describe an immunmofluorometric assay for the measurement of PTH-(1-84) based on a chicken egg yolk-derived amino-terminal antibody bound to microtiter plates by an anti-chicken Ig monoclonal antibody. As tracer antibody we employed a Europium-labelled carboxyl-terminal specific monoclonal antibody produced from a mouse immunized with hPTH-(53-84)-BSA conjugate. The assayincluded an initial overnight incubation of the sample and the solid phase-bound amino-terminal antibody, followed by washing and addition of the tracer antibody, and an additional two hours of incubation prior to fluorescence reading. The least-detectable dose was in the order of 2.5 pg/.ml and preliminary studies in 40 normal adults showed values in the range of 4 to 70 pg/ml; fo 12 patients with surgery-proven primary hyperparathyroidism values ranged from 109 to 743 pg/ml and for 34 patients with humoral hypercalcemia of malignancy from 2.5 to 66 pg/ml. We conclude that this assay, with its increased sensitivity and specificity, will be a valuable tool in the study of PTH secretion in normal and pathological situations

Parathyroid hormone secretory reserve in patients submitted to 131-iodine therapy for hyperthyroidism

Twelve euthyroid patients who had treated with I for hyperthyroidism due to Fraves' disease and six normal controls were submitted to an EDTA infusion test. Ionized calcium and parthyroid hormone were measured in serum samples collected every 10 min during the 2-h-test. Basal values for calcium (1.22 ñ 0.03 vs 1.23 ñ 0.03 pmol/l, mean ñ SD, controls vs patients) and parathyroid hormone (3.3 ñ 0.65 vs 5.5 ñ 2.32 pmol/l_ as well as maximum response during infusion (1.01 ñ 0.04 vs 1.01 ñ 0.05 for calcium and 12.0 ñ 2.2 vs 13.1 ñ 3.7 for parathyroid hormone) were not significantly different. We conclude that I treatment for hyperthyroidism due to Graves' disease had no effect on the parathyroid gland secretory reserve of the patients studied

Circulating molecular forms of parathyroid hormone in primary and secondary hyperparathyroidism

To study the circulating forms of parathyroid hormone (PTH), sera from 5 patients with primary hyperparathyroidism (PHP) and 12 patients with secondary hyperparthyroidism due the chronic renal failure (SHP) were submitted to gel filtration chromatography. The eluent samples were analyzed using two sequence-specific radioimmunoassays (RIA), one amino-terminal (NH2), the other carboxyl-terminal (COOH). The results obtained with the NH2RIA showed a single molecular form in both groups co-eluting with the intact hormone. The COOH assay identified several molecular forms with a broader distribution in the SHP patients. These results confirm the diagnostic superiority of the NH2 assay under both conditions