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Biomedical subjects

O L Silva

Publications and source records attributed to O L Silva.

At least 19 recordsLinked to original sources

Electrical field stimulation improves bone mineral density in ovariectomized rats.

Osteoporosis and its consequent fractures are a great social and medical problem mainly occurring in post-menopausal women. Effective forms of prevention and treatment of osteoporosis associated with lower costs and the least side effects are needed. Electrical fields are able to stimulate osteogenesis in fractures, but little is known about their action on osteoporotic tissue. The aim of the present study was to determine by bone densitometry the effects of electrical stimulation on ovariectomized female Wistar rats. Thirty rats (220 +/- 10 g) were divided into three groups: sham surgery (SHAM), bilateral ovariectomy (OVX) and bilateral ovariectomy + electrical stimulation (OVX + ES). The OVX + ES group was submitted to a 20-min session of a low-intensity pulsed electrical field (1.5 MHz, 30 mW/cm(2)) starting on the 7th day after surgery, five times a week (total = 55 sessions). Global, spine and limb bone mineral density were measured by dual-energy X-ray absorptiometry (DXA Hologic 4500A) before surgery and at the end of protocol (84 days after surgery). Electrical stimulation improved (P < 0.05) global (0.1522 +/- 0.002), spine (0.1502 +/- 0.003), and limb (0.1294 +/- 0.003 g/cm(2)) bone mineral density compared to OVX group (0.1447 +/- 0.001, 0.1393 +/- 0.002, and 0.1212 +/- 0.001, respectively). The OVX + ES group also showed significantly higher global bone mineral content (9.547 +/- 0.114 g) when compared to both SHAM (8.693 +/- 0.165 g) and OVX (8.522 +/- 0.207 g) groups (P < 0.05). We have demonstrated that electrical fields stimulate osteogenesis in ovariectomized female rats. Their efficacy in osteoporosis remains to be demonstrated.

Absorptiometry, Photon↗

Serum procalcitonin as an index of inhalation injury in burns.

The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal-region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury-associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients.

Biomarkers↗

Calcitonin as a marker for diethylnitrosamine-induced pulmonary endocrine cell hyperplasia in hamsters.

Immunoreactive calcitonin (iCT) has been localized in solitary endocrine cells and in clusters of these cells, called neuroepithelial bodies, in human and hamster lungs. It has been demonstrated that hyperplasia of hamster lung endocrine cells occurs following exposure to diethylnitrosamine (DEN), a systemic carcinogen. In the present study we have investigated iCT as a hormonal correlate of DEN-induced pulmonary endocrine cell hyperplasia in hamsters. Hamsters were given 3 mg of DEN per animal, subcutaneously, twice a week and then serially sacrificed at 2, 4, 8, and 12 weeks. By immunocytochemistry, iCT-containing cells could be demonstrated in thyroids, tracheal glands, and throughout the airway epithelium. At 8 or 12 weeks of DEN exposure, one to eight neuroepithelial bodies with iCT-containing cells were identified per square centimeter of lung sections, in contrast to zero to one neuroepithelial bodies/cm2 in control hamsters. By radioimmunoassay, pulmonary iCT increased significantly at 8 weeks of DEN exposure, amounting to 3.5-fold the control values at 12 weeks. Serum iCT increased at 4 weeks of exposure and by 12 weeks had tripled (183 +/- 62 pg/ml, mean +/- SD, p less than 0.001), as compared with control animals. Subsequently, DEN was stopped for 4 weeks, and the levels of both serum and lung iCT decreased, although they remained higher than those of controls. The serum and lung iCT of control hamsters was constant throughout the experiment (49 +/- 26 pg/ml and 1754 +/- 489 pg/gm of wet weight, mean +/- SD, respectively). Thyroidal iCT levels of exposed hamsters did not differ from those of the controls; both increased progressively. The DEN-exposed animals had retarded growth as compared with the controls. Column chromatography using superfine Sephadex G-75 demonstrated that both DEN-exposed and control lungs contained iCT with a predominant molecular size corresponding to the dimer of synthetic human calcitonin; whereas thyroidal iCT was mostly monomeric (approximately 3,500 daltons). The increase of pulmonary iCT correlates well with the 4-fold increase of pulmonary endocrine cells, reported earlier following similar DEN exposure. We conclude that iCT levels of hamster sera and lungs can be used as a biochemical parameter to monitor hyperplasia of the pulmonary endocrine cells in these animals.

Animals↗

Calcitonin secretion by continuous cultures of small cell carcinoma of the lung: incidence and immunoheterogeneity studies.

A study was made of immunoreactive calcitonin (iCT) secretion by continuous cultures of small cell carcinoma of the lung (SCCL). Using an antiserum region specific for the midportion of the molecule, 9/12 cultures were found to secrete iCT. Gel filtration studies were performed on both supernatant fluid (SF) and cell pellet (CP) extract from a culture secreting high levels of iCT. Multiple iCT fractions were found in the SF with the major fraction being of high molecular weight (MW). In contrast, the CP had apparently monomeric CT as its principal iCT fraction. These studies demonstrate frequent iCT secretion by SCCL cultures and significant disparities between the iCT moieties found extra- and intracellularly.

Animals↗

Hypothesis: the bronchial Kulchitsky (K) cell as a source of humoral biologic activity.

The bronchial Kulchitsky cells are scattered specific cells which lie close to the basement membrane of the bronchi and bronchioles. Electron microscopy reveals that they contain electron-dense granules similar to that seen in cells with a known endocrine function. In addition, experimentally induced degranulation of the K cell suggestive of a secretory process, and the likelihood that these cells are precursors of small cell lung carcinoma (which often elaborates humoral substances) has led to the postulate that this bronchial cell serves a humoral role of either a paracrine or endocrine nature. We have found that the bronchial K cell of man contains a calcitonin-like polypeptide which, immunologically and chemically, is not dissimilar to the hormone produced by the C cells of human thyroid. This finding may help explain the persistence of serum immunoreactive calcitonin (iCT) after total thyroidectomy, the fact that thyroidectomized man does not manifest any profound alteration of calcium metabolism, and why small cell cancer of the lung is frequently associated with hypercalcitonemia. In addition, the finding of K cell hyperplasia in chronic bronchitis and emphysema may explain the occurrence of hypercalcitonemia in patients with these diseases and some lung cancers of cell types other than the small cell variety. Further studies are needed to elucidate the role of K cell iCT, and to determine what other hormones might also be elaborated by this diffuse system of bronchial cells.

Bronchi↗

Increased serum and urinary calcitonin levels in patients with pulmonary disease.

Serum and urinary calcitonin levels were measured in patients with acute and chronic inflammatory diseases of the lung. Using both carboxyl terminal and midportion antisera, the incidence of increased immunoreactive values of this hormone was 68 percent for patients with emphysema, 59 percent for tuberculosis, and 89 percent for acute bacterial pneumonitis. In order to determine the source of the high levels of calcitonin, immunoperoxidase stains were made of sections of human lung; the hormone was found within the bronchial Kultschitzky cell (K cell). This suggests a specific endocrine role for the K cell, and may explain not only the high calcitonin levels in patients with inflammatory lung disease, but also the high levels associated with both carcinoid tumor and small cell carcinoma, which may originate from K cells. It is apparent that moderately high levels of calcitonin in a patient with pulmonary disease cannot always be associated with tumor.

Adult↗

Increased serum calcitonin in pregnancy.

Calcitonin, the hypocalcemic, hypophosphatemic polypeptide hormone of C cell origin, has been reported to be high in pregnant women at delivery. Levels of this hormone were determined by radioimmunoassay in 56 pregnant women in all trimesters and found to be above normal in 72 percent. Values were also increased during the first two days postpartum. Calcitonin levels were not correlated with serum calcium or phosphate, except in the first trimester when levels of this hormone were inversely correlated with serum phosphate. Perhaps the hypercalcitonemia of pregnancy serves to protect the maternal skeleton, while allowing the fetus to accumulate calcium.

Adult↗

Hypercalcitonemia in pernicious anemia.

Gastrin has been suggested as a natural secretogogue of the hormone calcitonin. We have found hypercalcitonemia in 55% of patients with pernicious anemia, and the gastrin levels, although usually increased, did not correlate.

Anemia, Pernicious↗

Immunoreactive calcitonin in cerebrospinal fluid of man.

We have detected immunoreactive calcitonin (iCT) in the cerebrospinal fluid (CSF) of normal individuals. Using an antibody with midportion recognition, the mean +/- S.D. of the cerebrospinal iCT in 27 normal subjects was 28 +/- 14 pg/ml. The mean serum iCT was 89 +/- 68 pg/ml, the CSF/serum distribution ratio being 0.31. There were no significant correlations between CSF iCT or serum iCT and the calcium, magnesium, phosphate, sodium, potassium or chloride in the CSF or serum. Although there was a trend for serum iCT values to be related to CSF iCT values, it did not attain statistical significance. The demonstration that the CSF contains iCT may have important physiologic implications, and its measurement offers a useful parameter to study its effects on calcium metabolism and/or other aspects of brain function.

Adult↗

Calcitonin in tissues of thyroidectomized monkey.

Immunochemical studies indicate that immunoreactive calcitonin (iCT) is present in many tissues of monkey following thyroidectomy (thx) (e.g. liver, thymus, lung). Extrathyroidal iCT may play a role in calcium metabolism.

Animals↗

Urine calcitonin levels in patients with bronchogenic carcinoma.

We demonstrated previously that high serum calcitonin values in bronchogenic carcinoma are useful clinically as a parameter of progress of the disease and response to therapy. After developing a procedure for the measurement of calcitonin in urine, we studied serum and urine levels in 41 patients with lung cancer, using both a carboxyl terminus and a midportion recognizing antiserum. In general, midportion antiserum was more useful. Urine calcitonin measurements alone were superior to serum in terms of numbers of patients having increased values with one or both antisera (76% vs 46%). When both antisera were used to assay both serum and urine, 90% of patients had abnormal values. Once a tissue diagnosis has been established, the radioimmunoassay of urinary calcitonin offers a new dimension to the utility of this hormone as a marker for bronchogenic carcinoma.

Adenocarcinoma↗

Immunocytochemical localization of calcitonin in Kulchitsky cells of human lung.

Because of the persistence of serum and/or urinary calcitonin in patients with thyroidectomies and the presence of high levels of immunoreactive calcitonin in the pulmonary tissue of primates with intact thyroids and primates on whom thyroidectomies were done, an immunocytochemical study was made of the lungs of human neonates. With the use of a specific antibody to calcitonin and the application of immunoperoxidase staining, reactivity was located within the bronchial and bronchiolar Kulchitsky (K) cells. This study, which strongly suggests that these cells have an endocrine role, offers a pathophysiologic rationale for the high calcitonin levels associated with the carcinoid tumor and small cell carcinoma, which may originate from the K cell. In addition, this study may explain why the removal of the thyroid gland is not followed by a profound change in calcium metabolism.

Bronchi↗

Calcitonin as a marker for bronchogenic cancer: a prospective study.

A prospective study was done of serum calcitonin (HCT) levels in 61 patients with bronchogenic cancer. Initially, 52% of patients had hypercalcitonemia. Hypercalcitonemia was not confined to patients with any particular histologic type. Seventy-eight percent of those with high calcitonin remained normocalcemic. There was no correlation between high calcitonin levels and osseous metastases. Selective thyroid venous sampling delineated two types of hypercalcitonemia: thyroidal and ectopic. To date, the ectopic type has been associated with the small cell bronchogenic carcinoma. High initial calcitonin levels decreased significantly in 75% of patients on antitumor therapy. In 13 evaluable patients calcitonin levels mirrored clinical status changes 67% of the time. Calcitonin may be a useful marker to assess the results of therapy in patients with bronchogenic cancer.

Bone Neoplasms↗