RESUMO

Measurement of the insulin-like growth factors (IGFs) and their binding proteins has become commonplace in the indirect assessment of the integrity of the GH axis. However, the relative effect of GH deficiency (GHD) on each component of the IGF axis and the merit of any one parameter as a diagnostic test have not been defined in a homogeneous population across all ages. We therefore measured IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3, and acid labile subunit (ALS) in 27 GHD subjects (aged 5-82 yr) from an extended kindred in Northeast Brazil with an identical GHRH receptor mutation and in 55 indigenous controls (aged 5-80 yr). The effect of GHD on the theoretical distribution of IGFs between the IGFBPs and the ternary complex was also examined. All components of the IGF axis, measured and theoretical, showed complete separation between GHD and control subjects, except IGFBP-1 and IGFBP-2 concentrations, which did not differ. The most profound effects of GHD were on total IGF-I, IGF-I in the ternary complex, and ALS. The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes. IGF-I in the ternary complex was determined principally by concentrations of ALS in GHD and IGFBP-3 in controls, implying that ALS has greater GH dependency. In the controls, IGF-II was associated primarily with IGFBP-3 and to a lesser extent with IGFBP-2, whereas in GHD the reverse was found. There was also a dramatic decline in the proportion of free ALS in GHD adults that was not evident in controls. As diagnostic tests, IGF-I in the ternary complex and total IGF-I provided the greatest separation between GHD and controls in childhood. Similarly, in older adults the best separation was achieved with IGF-I in the ternary complex, with free ALS being optimal in younger adults. Severe GHD not only reduces the amounts of IGFs, IGFBP-3, and ALS, but also modifies the distribution of the IGFs bound to each IGFBP. Diagnostic tests used in the investigation of GHD should be tailored to the age of the individual. In particular, measurement of IGF-I in the ternary complex may prove useful in the diagnosis of GHD in children and older adults, whereas free ALS may be more relevant to younger adults.

Assuntos

RESUMO

OBJECTIVE: A positive correlation between 24-h spontaneous growth hormone (GH) and cortisol secretion was previously reported in children. This observation prompted us to examine the relationship between physiological diurnal cortisol variation and the levels of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) under physiological conditions. DESIGN AND PATIENTS: Starting at 0800 h, blood was sampled every 20 minutes over 24 h for measurement of GH and cortisol concentration in nine non-GH- deficient boys as part of a protocol for the investigation of short stature. MEASUREMENTS: IGFBP-1 and insulin were measured in samples drawn every 4 h over the 24-h period while IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in samples collected at the end of the study. RESULTS: No correlation was observed between IGF-I or IGF-II and mean cortisol levels. IGFBP-1 concentrations showed a marked circadian variation that was superimposed on the circadian rhythm for cortisol while a significant positive correlation was found for single point measurements between IGFBP-1 concentrations and cortisol levels measured in the same sample (r = 0.53) or at the preceding 20 minutes (r = 0.43), 40 minutes (r = 0.47) and 2 h (r = 0.38), suggesting an interplay between cortisol and IGFBP-1. A negative correlation (r = - 0.54) was found between IGFBP-1 and insulin levels determined in the same sample. A negative correlation (r = - 0.93) was also found between IGFBP-2 levels and mean cortisol concentrations during the preceding 12 h. No correlation was observed between plasma IGFBP-3 measured by IRMA and mean cortisol levels. CONCLUSION: Our data indicate a clear correlation between cortisol and IGFBP-1 and IGFBP-2 levels. Thus, the interplay of spontaneous GH and cortisol secretion in children may involve changes in IGFBP-1 and IGFBP-2 levels.

Assuntos

RESUMO

Glucocorticoid excess is associated with a blunted GH response to GHRH. IGF-I levels in hypercortisolism are controversial and have been reported as low, normal or high. The aim of this study was to evaluate longitudinally time-dependent changes in the GH response to GHRH, IGF-I, IGFBP-3 and albumin values in patients during corticotherapy. Six patients received GHRH before and after one week and one month of prednisone administration (20-60 mg/d, orally). IGF-I, IGFBP-3 and albumin were determined in each test, at time 0. Ten normal controls were also evaluated in one occasion. There were no differences in basal GH values, GH response to GHRH, IGF-I and IGFBP-3 levels between controls and patients before starting corticotherapy. Albumin (g/l; mean+/-SE) values were lower in patients before treatment (31+/-4) than in controls (43+/-1). After one week of prednisone administration there was a significant decrease in peak GH (microg/l) levels (before: 18.8+/-7.4; 1 week: 5.0+/-1.3), which was maintained after one month (8.1+/-3.5). IGF-I (microg/l) levels increased significantly, from 145+/-23 to 205+/-52 after one week of therapy, reaching levels of 262+/-32 after one month. IGFBP-3 (mg/l) values did not increase significantly (before: 2.1+/-0.2; 1 week: 2.5+/-0.3; 1 month: 2.8+/-0.2). Albumin levels showed a significant rise both after one week (36+/-4) and one month (42+/-3) of corticotherapy. In summary, we observed a marked decrease in the GH response to GHRH after one week and one month of prednisone administration associated with an increase in circulating IGF-I and albumin values. The physiological implications of these findings are still uncertain. It is possible that glucocorticoids increase hepatic IGF-I and albumin synthesis, although other mechanisms may have a role.

Assuntos

RESUMO

Dysfunction of the alpha-tocopherol transfer protein causes ataxia with isolated vitamin E deficiency. A 14-year-old male patient presented with ataxia and mental symptoms caused by a homozygous (552G-->A) alpha-tocopherol transfer protein mutation. After initiation of high-dosage alpha-tocopherol therapy, the organic mental syndrome disappeared and cognitive function improved rapidly. Neurologic recovery, however, was slow and incomplete.

Assuntos

RESUMO

Crassulacean acid metabolism (CAM) plants are dependent on the organic acids that accumulate overnight in the vacuoles as a source of CO(2) during the daylight deacidification period, when stomata are closed and high irradiances generally prevail. We performed an integrative analysis of diurnal changes in gas exchange, chlorophyll fluorescence parameters and organic acid decarboxylation to understand the adjustments in photochemical and non-photochemical processes during the different CAM phases in Clusia hilariana Schlecht., a dominant tree species in the sandy coastal plains of southeastern Brazil. A linear relationship was obtained between the quantum yields of photochemical and non-photochemical quenching, irrespective of the CAM phase and prevailing irradiance. Degradation of malic and citric acids during the midday stomatal closure period could lead to potential CO(2) fixation rates of 23 &mgr;mol m(-2) s(-1), whereas CO(2) losses, measured as CO(2) evolution, corresponded to about 3% of this value. Thus, decarboxylation of malate and citrate provided high internal CO(2) concentrations during phase III of CAM, even though the stomata were closed, allowing optimal utilization of light energy, as indicated by the non-saturating electron transport rates (ETR) in the light response curves, with highest rates of ETR occurring at midday in the diurnal curves. At the transition from phase III to IV of CAM, depletion of internal CO(2) sources and low stomatal conductances, which restricted the supply of exogenous CO(2), reduced the demand for photochemical energy to drive carbon assimilation. This was compensated by increases in thermal energy dissipation as indicated by higher rates of non-photochemical quenching, while high irradiances still prevailed. Shifts in the CAM phases and changes in protective thermal dissipation potential allowed C. hilariana to match changes in PPFD patterns for leaves of different orientations. Evidence that most of the decline in photochemical efficiency was probably related to the fast-relaxing component of non-photochemical quenching is provided by the high values of the quantum yield of photosystem II after 20 min of relaxation in darkness, and an almost complete recovery after sunset. These adjustments in photosynthetic machinery minimized the danger of photo-inhibition in C. hilariana, which is commonly found in fully exposed habitats.

RESUMO

OBJECTIVE: Several abnormalities in the GH response to pharmacological stimuli have been described in hyperthyroidism. Both normal and high serum IGF-I levels have been reported, as well as a decrease in IGF-I bioactivity. We have evaluated the GH response to GH-releasing hormone (GHRH) in hyperthyroid patients and the effects of hyperthyroidism on serum IGF-I levels. The possible relations between nutritional status, thyroid hormones and IGF-I levels were also investigated. We also studied the influence of long-term beta-adrenoceptor blockade on the GH response to GHRH in these patients. DESIGN: In 18 hyperthyroid patients and in 12 control subjects, GHRH (100 micrograms) was administered as an i.v. bolus injection. Eight hyperthyroid patients and 8 control subjects received 50 micrograms GHRH i.v. Seven hyperthyroid patients were reevaluated after beta-adrenoceptor blockade. IGF-I and albumin levels were measured initially in all hyperthyroid patients and control subjects. Body composition was determined in 11 hyperthyroid patients and in a group of 33 matched normal controls. PATIENTS: Hyperthyroid patients were compared to control subjects. MEASUREMENTS: GH, TSH and free T4 were measured by immunofluorometric assay. IGF-I, total T3 and total T4 were measured by radioimmunoassay. Body composition was determined using a dual-energy X-ray absorptiometer. RESULTS: The GH response to 100 micrograms GHRH in hyperthyroid patients was blunted compared to control subjects. The mean peak GH levels and the area under the curve were significantly lower in hyperthyroid patients compared to control subjects (11 +/- 1 vs 27 +/- 5 micrograms/l and 820 +/- 113 vs 1879 +/- 355 micrograms/l 120 min, respectively; P < 0.01). IGF-I levels were significantly reduced in hyperthyroid patients compared to controls (131 +/- 10 vs 201 +/- 16 micrograms/l, respectively; P < 0.01). Ideal body weight, serum albumin levels and the lean body mass were also reduced in hyperthyroid patients. After beta-adrenoceptor blockade there were no changes in the blunted GH response to GHRH in hyperthyroid patients. CONCLUSION: Our data suggest that the blunted GH response to GHRH in hyperthyroidism is apparently not related to circulating IGF-I levels. It is possible that nutritional factors could play a role in the reduced circulating IGF-I levels found in these patients.

Assuntos

RESUMO

A hand dynamometer was used to measure muscle strength in 207 patients admitted to the Gastroenterology service of a general hospital. Validation of international standards in a normal population of both sexes and different ages revealed that our normals perform at the 25% percentile of international values. Results were correlated with other measurements of nutritional status, namely anthropometric measurements, serum albumin level and tuberculin test. Compared to normals, muscle strength was significantly (p < 0.01) lower in patients with body mass index under 19, cutaneous tricipital folding < 85%, brachial circumference < 85%, and serum albumin < 3.5 g/dl. No difference in muscle strength between tuberculin positive or negative subjects was observed. None of the nutritional parameter was helpful to predict complications in patients submitted to surgery. Thus, muscle strength is a useful parameter to evaluate nutritional status but, similar to other measurements, is not predictive of surgical complications.

Assuntos

RESUMO

Structural brain abnormalities in schizophrenia have been reported by several computertomographic (CT) studies. However the prevalence and the localization of the abnormalities vary widely among studies. These differences might stem from samples heterogeneity, from the choice of the CT parameter to be investigated and from the use of different criteria for defining abnormalities. In spite of some contradictory findings, it seems established that at least one subgroup of schizophrenic patients shows mild or moderate brain atrophy; this subgroup might be characterized by a chronic course of the disease, poor response to neuroleptic therapy, and the presence of other neurodiagnostic signs of a diffuse brain dysfunction such as neuropsychological impairment, EEG abnormalities and neurological "soft signs". Atrophic findings have been observed in young schizophrenic patients at the first onset of the disease, indicating that the development of the structural abnormalities are not a consequence of a chronic disease and treatment. Schizophrenics with atrophy are unlikely to have a genetic loading (family history) with schizophrenia and they present more frequently pregnancy and birth complications as well as brain trauma in the first years of development. Because schizophrenics with brain atrophy might represent a more homogeneous subgroup with regard to clinical and aetiopathological variables, it is still an important task to identify more precisely these patients on the basis of CT data and then to study the features that could characterize this subgroup.

Assuntos

Assuntos

Assuntos

Assuntos