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Biomedical subjects

D Giannella-Neto

Publications and source records attributed to D Giannella-Neto.

24 records · Page 2Linked to original sources

Glucocorticoids and glucose metabolism: hepatic glucose production in untreated Addisonian patients and on two different levels of glucocorticoid administration.

Plasma glucose, insulin levels and hepatic glucose production rates were studied after an overnight fast in six Addisonian patients in three different conditions: off replacement treatment, on substitution therapy and on high-dose glucocorticoid treatment. For comparison eight normal subjects were evaluated in basal conditions. Fasting plasma glucose and hepatic glucose production did not change significantly with either level of glucocorticoid treatment when compared to the untreated state and the normal controls, but there was a significant increase in plasma glucose levels in the high-dose cortisone-treated Addisonian patients when compared to the untreated state. Insulin levels were significantly lower in the untreated state and significantly higher in the high dose-treated patients when compared to the normal controls. It is suggested that in these experimental conditions the peripheral actions of glucocorticoids are predominant over the hepatic effects by virtue of their ability to produce secondary changes in insulin levels, keeping the hepatic glucose production constant.

Addison Disease↗

Role of obesity and hyperinsulinemia in the insulin resistance of obese subjects with the clinical triad of polycystic ovaries, hirsutism and acanthosis nigricans.

The insulin resistance of 4 nonobese and 8 obese patients with polycystic ovaries, hirsutism and benign acanthosis nigricans, and of 6 'obese normal' apart from obesity and 10 normal female subjects was evaluated by means of an intravenous insulin tolerance test and by measuring basal and insulin responses to an oral glucose load. The patients with polycystic ovaries, hirsutism and acanthosis had a decreased hypoglycemic response to exogenous insulin. The subjects with polycystic ovaries presented a significantly greater mean glucose response area for the same or greater mean insulin response area than the obese or nonobese normal subjects. The insulin resistance in the patient with polycystic ovaries, hirsutism and acanthosis nigricans could not be exclusively ascribed to a reduced receptor number, but also appeared to be due to a simultaneous postbinding defect probably related to the high insulin levels in patients with polycystic ovaries be they obese or not. The elevated plasma androgens and the presence of acanthosis found in these patients are likely also related to the hyperinsulinemia. To evaluate the influence of obesity, obese and nonobese patients with acanthosis nigricans and polycystic ovaries were compared. Higher insulin levels were found in the thin subjects, which could explain their greater insulin resistance and more severe hyperandrogenism. The comparison between obese patients with and those without acanthosis nigricans and polycystic ovaries suggested that, despite similar insulin levels, the greater known duration of obesity (probably also of the hyperinsulinemia) of the former was a possible explanation for their more intense insulin resistance and higher testosterone levels.

Acanthosis Nigricans↗

X-chromatin in congenital virilizing adrenal hyperplasia.

X-chromatin body (XCB) frequencies in oral mucosa were investigated in 14 female patients with the simple non-salt-losing form of congenital virilizing adrenal hyperplasia (CVAH) due to 'partial' 21-hydroxylase deficiency (CVAH-type I), using toluidine blue (TBS) and Feulgen's stains (FS). They were found to be lower than normal controls by both TBS (12.6 +/- 1.73 vs 18.38 +/- 0.41) and FS (13.60 +/- 2.16 vs 17.94 +/- 0.76) methods. After 4-5 weeks on glucocorticoid therapy, XCB frequencies overlapped with those of normal controls using both TBS (16.54 +/- 1.76) and FS (17.09 +/- 1.98). Karyotypes performed in 8 of the 14 cases showed a normal female pattern. Two possible interpretations are proposed: First, variations of XCB counts may reflect the average nuclear size of the cell populations studied. Second, high androgen levels found in untreated cases with CVAH-type I might lead to partial chromosome depiralization and increasing euchromatic areas. At present the first possibility appears more likely.

Adolescent↗

Pattern of thyrotropin and thyroxine plasma concentrations during the 24-hour sleep-wake cycle in the male rhesus monkey.

The 24-h pattern of the plasma TSH concentration was investigated in five male rhesus monkeys prepared chronically with right atrial catheters and electroencephalogram (EEG) electrodes. The preparation allowed frequent blood sampling (every 15 min), TV monitoring, and EEG recording from the adjacent room for extended periods of time from undisturbed animals. In addition, nap deprivation, 5 h total sleep deprivation, and specific sleep stage deprivation experiments were performed in order to test their influence on the TSH pattern. T4 was also determined in approximately half of the profiles during undisturbed conditions. Both TSH and T4 patterns consisted of low amplitude, high frequency fluctuations which, however, did not exceed the assay variation. TSH showed superimposed higher amplitude spikes at unpredictable times (0-5/24-h). Intra- and interanimal variabilities of both TSH and T4 patterns were high. Power spectral maxima of the TSH time series indicated periodicities between 30-75 min which were not significant. No nyctohemeral difference in the TSH or T4 pattern or their mean concentrations was found, and there was no consistent pattern of a circadian cycle. Independent changes of average TSH and T4 concentrations were seen in 5 of the 16 profiles during undisturbed conditions, under which both hormones were determined. Cross-correlation analysis of the hormonal time series revealed no significant relation between TSH and T4 patterns. The deprivation procedures had no significant influence on the day or nighttime pattern of TSH. Cross-correlation analysis showed no relation between TSH and either activity during the day or sleep stages during the night. It is concluded that in the rhesus monkey, in contrast to man, TSH secretion shows no circadian variation and is not influenced by the sleep-wake cycle.

Animals↗

Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome.

Visceral adipose tissue (VAT) imaged by computed tomography (CT) or magnetic resonance imaging (MRI) is associated with the metabolic syndrome features, being morphologically and functionally different from subcutaneous adipose tissue (SAT). Insulin effect is lower and catecholamine effect higher in visceral adipose tissue, with its metabolites and its secretions draining through portal system, partially at least, to the liver. Thus, visceral cells transfer and release fatty acids more extensively, have increased glucocorticoid and reduced thiazolidinedione responses, produce more angiotensinogen, interleukin-6 and plasminogen activator inhibitor-1, and secrete less leptin and adiponectin than SAT. Furthermore, there are regional differences in the intrinsic characteristics of the preadipocytes, with those of SAT presenting greater differentiation and fat cell gene expression but less apoptosis than that of VAT. All features contribute to the morbidity associated with increased VAT. To evaluate the relationship between VAT and components of the metabolic syndrome, 55 non-diabetic women, 11 lean (VAT < 68 cm 2) and 44 obese were studied. The obese with VAT within the normal range (VAT < or = 68 cm 2) had higher BMI, WHR, BP and resistance to FFA suppression during oGTT in comparison to the lean controls. The obese with VAT > 68 cm 2 compared to those with VAT < or = 68 cm 2 had similar body mass index (BMI) but significantly higher in vivo homeostasis model assessment for insulin resistance (HOMA IR ) results and triglycerides. By pooling all data, correlation analysis indicated that VAT contributes more to insulin resistance (HOMA IR ) than SAT does, but not when insulin-suppressed plasma free fatty acids during oral glucose tolerance test as an index of insulin resistance are taken into consideration.

Adipose Tissue↗

Growth hormone and insulin-like growth factor I axis and growth of children with different sickle cell anemia haplotypes.

BACKGROUND: The purpose of this study was to examine the relationships between growth in children with sickle cell anemia and the different beta-globin haplotypes, as well as components of the insulin-like growth factor (IGF)/insulin-like growth factor binding protein (IGFBP) axis. PATIENTS AND METHODS: Growth parameters and plasma concentrations of growth hormone (GH), IGF-I, and IGFBP-3 were studied in 41 children with sickle cell anemia whose haplotypes were defined. RESULTS: Plasma concentrations of IGF-I (total, free, and free/total fraction) and IGFBP-3 were significantly reduced in all patients with sickle cell anemia compared with the healthy children. Patients with the CAR/CAR haplotype had significantly lower mean growth velocity compared with those with Ben/Ben. When the GH/IGF axis elements were compared in relation with the different haplotypes, total IGF-I levels in CAR/CAR patients were significantly lower compared with levels in patients with Ben/Ben. A positive correlation was found between hematocrit and total IGF-I and between fetal hemoglobin percentages and the z-scores for total IGF-I and IGFBP-3. There was a positive correlation between age, weight, height, bone age, and the various elements of the GH/IGF-I axis when all groups were considered, although the correlation was lost when the auxologic data were expressed as standard deviation score for age. Growth velocity and the z-score for growth velocity were not correlated with any element of the axis. CONCLUSIONS: The positive relationship between hematocrit and fetal hemoglobin percentages with total IGF-I, free/total IGF-I, and IGFBP-3 in patients with sickle cell anemia could show that the delayed growth of these patients may be linked to intrinsic factors of the disease, which also determine the low circulating concentrations of the various elements of the GH/IGF-I axis. It is reasonable to assume that decrease of total IGF-I concentrations in patients with CAR/CAR haplotype is secondary to the severity of the disease.

Adolescent↗