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Osmar Monte

Publications and source records attributed to Osmar Monte.

10 recordsLinked to original sources

Antiproliferative and apoptotic potencies of glucocorticoids: nonconcordance with their antiinflammatory and immunosuppressive properties.

Relative antiinflammatory and immunosuppressive potencies of glucocorticoids (GC) were previously well defined. Nonetheless, GC also regulate cell proliferation and programmed death (apoptosis). The aim of this study was to determine the relative potency of different GC on the modulation of cell survival. The GC-sensitive lymphoblast cell line CEM-c7/14 was submitted to 48 h-exposure to GC (dose-response curve from 10(-8) to 10(-5) M). Cell survival was analyzed employing the DimethylTiazol-Tetrazolium (MTT) test. For each GC at least 4 experiments were performed in quadruplicate. Responses to different GC at the same molarity were analyzed by ANOVA on Ranks. Cell responses to the same GC in different concentrations were tested by repeated measures ANOVA. The EC50 for each GC was calculated with the GraphPad Prism 3.0 software. The use of low concentrations (10(-8) and 10(-7) M) of hydrocortisone and methylprednisolone determined a similar effects on cell survival, which was less prominent than that observed with betamethasone, budesonide or momethasone. Momethasone was the most potent GC, inducing the most intense dexamethasone reduction on cell survival at the lowest concentration (10(-8) M). Momethasone and methylprednisolone were the two GC with the strongest impact on cell survival. Our findings suggest that antiproliferative and apoptotic potencies of GC are different from those previously reported antiinflammatory and immunosuppressive actions.

Analysis of Variance↗

[Mutation screening in Angiotensin II receptors, AGTR1 and AGTR2, and evaluation of AGTR1 polymorphisms C573T and A1166C in patients with premature adrenarche].

Precocious pubarche is the appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The most frequent etiology is idiopathic precocious adrenarche, suggested, after long-term follow-up, to be associated with metabolic syndrome. One of the factors involved in the genesis of precocious adrenarche is Angiotensin II (Ang II), which promotes cell proliferation and steroidogenesis through type 1 (AT1) and type 2 (AT2) receptors. In order to study Ang II receptors mutations, 50 children with idiopathic precocious adrenarche were evaluated and compared to a control group of normal individuals. Mutations were not detected in the AGTR1 and AGTR2 genes; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3' untranslated region). The polymorphic allele T573 was found in 35% of the patients and 38% of controls. The polymorphic allele C1166 was present in 24% of the patients and 26% of controls. There was no statistical difference between groups. There was also no correlation between the polymorphisms and clinical and laboratory findings, as well as their family history of metabolic syndrome.

Adrenarche↗

[Influence of propyl-thiouracil-induced hypothyroidism on rat gingival mucosa].

This work aimed at verifying the influence of propyl-thiouracil (PTU)-induced thyroid hormone deficiency on gingival mucosa of young male rats, measuring total protein concentration, collagen content and DNA concentration as indices of cellular population. Fifty Sprague-Dawley rats were used. The animals were grouped in: PTU-treated (i.p. 10 mg/d) and control rats (C). The experience was maintained for a period of 10 weeks. Total protein content of gingival mucosa tissue was determined by the Lowry method; hydroxyprolin rate, as prototype amino acid of collagen, was determined using the Newman method, and DNA concentration was measured by Burton's methodology. The results showed decreased amounts of PTU-treated rats gingival total protein content (PTU= 41.23 +/- 24.05 vs. C= 63.36 +/- 18.05); no alterations were seen in hydroxyprolin concentration neither in DNA content of PTU treated rats, respectively (PTU= 2.18 +/- 1.48 vs. C= 2.29 +/- 1.51) and (PTU= 0.33 +/- 0.19 vs. C= 0.46 +/- 0.41). Thus, PTU treatment promotes a decrease in total protein content of rat gingival mucosa that may be interpreted as a decrease in protein synthesis induced by the hypothyroid condition, but with no alteration either in collagen or nucleic acid rates.

Animals↗

[Dopaminergic and somatostatinergic pathways decrease serum thyrotropin in rats bearing the 256-Walker mammary carcinoma].

The hypothalamus-pituitary-thyroid axis was studied in rats with the "low T(3) syndrome" caused by the implantation of the Walker-256 mammary carcinoma. Male adult rats were injected s.c. with 1 x 106 viable tumoral cells and killed 10 days later. The tumor development was associated with decreased thyroid activity characterized by a approximately 15% reduction in the nuclear area of the thyrocytes and 131I-thyroid uptake (down by approximately 50%), as well as about 70% lower serum levels of T4 and rTg. The functional thyroidal response to exogenous TSH was decreased in the tumor-bearing rats, as well as the rTSH secretion in response to TRH (50 microg/kg). To investigate the role of other hypothalamic neuromediators in this process, tumor-bearing rats received an i.v. injection of metoclopramide (5 mg/kg) and/or physostigmine (12.5 microg/kg), with or without concomitant stimulus with TRH. Each drug improved the rTSH response to TRH, which in the case of physostigmine, almost normalized. When both drugs were injected simultaneously the rTSH response to TRH returned to normal. Thus, in addition to the well known alterations in the extrathyroidal metabolism of thyroid hormones, TSH secretion is decreased in rats with the Walker-256 tumor, indicating a generalized reduction in the thyroid function.

Animals↗

Abnormal inhibin A and inhibin B secretion in obese women with and without insulin resistance.

AIM: The present study aimed to establish inhibin A and B serum levels during the menstrual cycle of obese women, and its usefulness as an index of luteal-phase follicular development. MATERIALS AND METHODS: Twenty-one obese patients (mean body mass index: 34.9+/-3.7 kg/m2; range: 30.0-45.0 kg/m2) were submitted to basal hormonal measurements and an oral glucose tolerance test after challenge with 75 g glucose. Progesterone and inhibin A and B levels were determined 5-7 days after the menstrual cycle and 7 days prior to expected menses. RESULTS: As expected, an increase in inhibin A and a decrease in inhibin B were observed when first-phase samples were compared with samples obtained after 15-20 days. On the other hand, the percentage variation of both inhibin A and B was at least four times smaller than the values for normal women described previously by other authors employing the same enzyme-linked immunosorbent assays. A small number of obese women presented ovulatory cycles characterized by progesterone concentration higher than 5.8 ng/ml. The percentage elevation (>190%) of inhibin A in the second samples was in agreement with the progesterone levels, but it seemed to be more sensitive for the detection of follicle luteinization. CONCLUSION: We conclude that obese women present less percentage variation of both inhibin A and B during the menstrual cycle, associated with a low frequency of ovulatory cycles. In obese women, the percentage increase of inhibin A can represent an additional marker to recognize follicle luteinization.

Adolescent↗

[Radioactive iodine therapy for Graves' disease in childhood and adolescence].

While the diagnosis of Graves' disease in childhood and adolescence is relatively straightforward, its treatment remains controversial. The first choice therapy is the use of anti-thyroid drugs, although side effects are more frequent than in adults and remission is low. Surgery is not usually indicated as initial treatment. Instead, it is generally recommended after recidive of the disease or due to side effects of medical treatment. The use of radioiodine therapy is increasing in this age group, especially in North America, and control of the hyperthyroidism is achieved in 3 to 6 months in 90% of the cases. There is no evidence that radioiodine therapy is associated with a higher risk of thyroid cancer, and the occurrence of side effects is lower than surgery. Based on the positive results obtained with this therapy, patients with poor responsiveness to medical treatment should be considered for early radioiodine therapy.

Adolescent↗

Fast acquisition sagittal T1 magnetic resonance imaging (FAST1-MRI): a new imaging approach for the diagnosis of growth hormone deficiency.

Routine magnetic resonance imaging (MRI) is an established standard method to investigate the etiology of pituitary insufficiency. Among the anatomic abnormalities usually observed, ectopic hyperintense signal on T1 sequence is the most frequently associated with pituitary dysfunction. We developed a new protocol (FAST1-MRI) which is able to detect anatomic hypothalamic-pituitary abnormalities with 100% concordance when compared to the routine MRI protocol. FAST1-MRI takes only 3.25 minutes, and is performed without contrast, sedation or anesthesia. We studied 17 controls and 31 patients with growth hormone (GH) deficiency (18/31 with abnormal MRI). Patients with ectopic hyperintense signal were shorter in height, had lower IGF-I and IGFBP-3 levels, and reduced GH response after clonidine. In conclusion, we describe a new simplified MRI protocol that we propose should be used in the diagnosis of GH deficiency.

Adolescent↗

Partial glucocorticoid resistance in obese children detected by very low dose dexamethasone suppression test.

The effects of glucocorticoids (GC) are mediated by the activation of specific receptors that can be quantified in vitro by several laboratory tests. In vivo, other tests to determine GC sensitivity have been described, but only employing pharmacological doses. In this study, we used a very low dose of dexamethasone, an in vivo model to assess individual GC sensitivity. Fifty-five obese children and adolescents and 17 controls were studied. The patients were submitted to four 12-h urine collections, starting at 22:00 h; dexamethasone was administered orally at the end of the second urine sample. Patients were divided in the following groups: group Ob75 (n = 29) and the control group (n = 17) received dexamethasone 75 microg/m2, and group Ob150 (n = 26) received dexamethasone 150 microg/m2. Urinary cortisol was determined by RIA and expressed as microg/m2/12 h. All patients and controls showed a circadian rhythm before GC, which was maintained after dexamethasone only in controls. In the obese patients the circadian rhythm was abolished following both doses of dexamethasone, but more prominently with the dose of 150 microg/m2. In the obese group given 75 microg/m2, urinary cortisol inhibition was only observed in the first 12 h after dexamethasone, suggesting a partial and shorter suppression of the hypothalamic-pituitary axis. In both control and obese patients, the very low dose of dexamethasone was able to create a gradient of cortisol suppression that could be useful to identify an individual's sensitivity to glucocorticoids.

Administration, Oral↗

Molecular detection of XO - Turner syndrome.

Turner syndrome is caused by haploinsufficiency of the short arm of X-chromosome, and is usually diagnosed by karyotyping. This procedure is time-consuming, expensive and unfeasible for population screening. We propose molecular detection of 45XO Turner patients based on the ability of HpaII, a methylation sensitive endonuclease, to induce the cleavage of non-methylated DNA in the active X-allele. Genomic DNA was obtained from 22 patients with Turner syndrome confirmed by karyotype (45XO, N = 18; 45XO/46XX, N = 4). After digestion, DNA was amplified with primers directed to exon 1 of the androgen receptor (AR) gene and to the GAPDH control gene. Normal control females or mosaic patients, with a second methylated X-chromosome, escaped from HpaII digestion and produced a band corresponding to AR gene amplification. 45XO patients have just one active non-methylated X-chromosome, completely digested by HpaII, thus preventing the amplification of the AR gene. Three of the 45XO cases gave amplified bands, suggesting low-frequency mosaicisms that are not detected by karyotyping. Compared to classical karyotype studies for the detection of 45XO Turner patients, this new molecular method is simpler, faster and less expensive.

Base Sequence↗

[Evaluation of the hypothalamic-pituitary-thyroid axis in children with Down syndrome].

OBJECTIVE: To determine the thyroid stimulating hormone (TSH) secretion in children with Down syndrome (DS), who do not present clinical and laboratory evidence of classical hypothyroidism and concomitant undetectable antibodies. METHODS: Fourteen children with DS with a mean age of 3.4 (+/- 1.8) years were studied. Patients with classical hypothyroidism or hyperthyroidism or those with positive antithyroid antibodies were excluded. The DS group was compared to a control group of 16 children with a mean age of 11.8 (+/- 3.8) years, diagnosed as having familial short stature or constitutional growth delay. Both groups underwent hormonal measurements at basal condition to determine serum TSH, T3, T4, free T4 and prolactin concentrations and after stimulation with thyrotropin releasing hormone (TRH). Thyroid hormones concentrations were also compared when children with DS were subdivided into two groups according to their basal TSH levels. RESULTS: Basal TSH and prolactin levels were significantly higher in DS group. After stimulation with TRH, TSH peak was higher in the DS group. The number of patients presenting basal TSH levels higher than 5 microU/mL and TSH peaks higher than 30 microU/mL were significantly higher in the DS group. CONCLUSIONS: Children with Down syndrome present frequent increase in basal TSH concentrations, despite the presence of normal basal thyroid hormones levels and negative antithyroid antibodies. Most of them (65%) show early intense response after TRH stimulation. Our data demonstrate that in spite of the absence of classic hypothyroidism and/or antithyroid antibodies, an abnormal pattern of TSH secretion occurred in patients with Down syndrome, possibly related to hypothalamic dysfunction.

English Abstract↗