Biotin deficiency in protein-energy malnutrition

Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM). Average plasma biotin concentrations were lower in 16 malnourished children (10 with marasmus, 3 with kwashiorkor and 3 with marasmic kwashiorkor) than in 31 controls. Lymphocyte mitochondrial carboxylase activities were studied in 11 controls and in 10 patients with PEM; on the average, they were lower in the patients. Their activation indices (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were higher in PEM. All these differences were statistically significant. None of these parameters were age-dependent in a range between 3 and 72 months. Carboxylase activities and plasma biotin levels increased to normal during nutritional recovery in two malnourished patients who were further studied. These results suggest that there is biotin deficiency in severe PEM. Urinary biotin concentrations, expressed per g of creatinine, were higher in the patients than in the controls; this may have been caused by increased renal clearance or by the reduced creatinine excretion which occurs in malnourished individuals. It will be important in future studies to determine the relative contribution of biotin deficiency to the malnourished phenotype.     

HIV-1 and hepatitis B virus infections in adolescents lodged in security institutes of Buenos Aires

The goal of this study was to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) infections in street youth lodged in security institutes, from February 1992 to March 1995, to correlate these infections with nontherapeutic drug use, and to compare these results with a previous study done in a similar population. A total of 1460 white adolescents, 276 females and 1184 males, were enrolled (mean age 16.6 years). Prevalence of HIV-1 was 4.58% and of HBV was 6.78%. The prevalence of dual HIV-1/HBV infection was 1.91%; the prevalence of HBV infection was significantly higher in HIV-positive subjects (p < 0.0000000, chi 2 = 136.17, OR = 13.37) than in those not infected with HIV-1. Prevalences were higher in males. Intravenous drug addiction proved to be a significant risk factor for both viruses (HIV-1, p < 0.0000000, chi 2 = 171.34, OR = 16.84; HBV, p = 0.000044, chi 2 = 16.67, OR = 3.17); 6.43% of the total population were intravenous drug users. Comparison of the current results with our previous study (1989-1992) showed that the prevalence of HIV-1, HBV, and concurrent HIV/HBV as well as intravenous drug addiction has decreased significantly in our current cohort (chi 2 = 134.85, p < 0.0000000; chi 2 = 126.62, p < 0.0000000; chi 2 = 110.05, p < 0.0000000; and chi 2 = 158.3, p < 0.0000000) respectively. Progress appears to have been made in the fight against acquired immunodeficiency syndrome (AIDS), and promising results have been obtained. However, if further viral spread is to be avoided, the emphasis on prevention should be energetically maintained.     

Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients

The purpose of this study was to evaluate the short-term efficacy of topical capsaicin treatment in patients severely affected by fibromyalgia. One hundred and thirty fibromyalgia patients were randomly divided into two groups. The control group, 56 women and 4 men who continued their medical treatment, and the capsaicin group, 70 women who apart from continuing their medical treatment, also underwent topical capsaicin 0.075 % 3 times daily for 6 weeks. At the beginning of the program, there were no significant differences between the two groups in any of the analyzed parameters. At the end of the treatment, there were significant improvements in the capsaicin group in the myalgic score (5.21 vs 3.8, p = 0.02) and global subjective improvement (22.8 vs 5 %, p = 0.001). Six weeks after the end of the treatment, the experimental group showed significant differences in Visual Analogue Scale of depression (5.63 vs 7.35, p = 0.02), Fibromyalgia Impact Questionnaire (67.89 vs 77.7, p = 0.02), role limitations due to emotional problems (36.17 vs 17.2, p = 0.05), Fatigue Severity Scale (6.2 vs 6.6, p = 0.04), myalgic score (3.94 vs 2.66, p = 0.02) and pressure pain threshold (79.25 vs 56.71, p = 0.004). In conclusion, patients severely affected by fibromyalgia can obtain short-term improvements following topical capsaicin 0.075 % treatment three times daily for 6 weeks.     

Acute administration of corticoids: a new and peculiar stimulus of growth hormone secretion in man

It is widely accepted that chronic administration of corticoids in man inhibits the GH response to all of the stimuli tested so far. To study the action of corticoids administered acutely, several dexamethasone challenge tests were performed, after which GH levels were measured for 7 h. In eight volunteers, administration of 4 mg dexamethasone (Dex), iv, induced a clear-cut GH release compared with saline administration. The secretion followed an unusual pattern; basal GH levels (1.5 +/- 0.1 micrograms/L) started rising 2 h after Dex injection, reaching a peak of 17.5 +/- 4.4 micrograms/L after 3 or 3.5 h. Peak levels were maintained until 5 h post-Dex and decreased thereafter. Similar data were obtained when Dex was administered to five volunteers at the dose of 8 mg, orally, with a 30-min delay of the GH peak (19.6 +/- 7.9 micrograms/L). To study whether there was a cholinergic input responsible for the Dex action, another group of eight volunteers underwent three Dex tests (4 mg, iv) on three occasions, followed 90 min later by the administration of placebo (control), atropine (0.5 mg, iv), or pyridostigmine (120 mg, orally). The Dex-induced GH peak (20.8 +/- 5.2 micrograms/L) was not significantly increased by pyridostigmine (cholinergic agonist) treatment (24.2 +/- 4.0 micrograms/L). The blockade of muscarinic receptors by atropine induced a delay in the Dex-induced secretory peak, which appeared at 5 h. However, the Dex-atropine GH peak (14.9 +/- 4.1 micrograms/L) was not different from the Dex-placebo one. In conclusion, Dex alone is able to induce a clear-cut GH secretion in man. The stimulus followed a peculiar time pattern, with peaks levels attained 3 h after either iv or oral administration.     

Depending on the time of administration, dexamethasone potentiates or blocks growth hormone-releasing hormone-induced growth hormone release in man

In humans, corticoids suppress growth hormone (GH) secretion elicited by a variety of stimuli, while in vitro they potentiate GH release. To further study this problem, the effect of two doses of dexamethasone on GH secretion elicited by GH-releasing hormone (GHRH) in 6 normal volunteers was studied. Each subject underwent three tests, on 3 separate days with GHRH 1-29 (1 microgram/kg i.v. at 12.00 h). On the control day, only GHRH was given, on the second day dexamethasone 4 mg i.v. was administered at 09.00 h (3 h before GHRH) and on the third day dexamethasone 8 mg p.o. was given 12 h before GHRH (at 00.00 h). The GHRH-induced GH peak was 9.9 +/- 2.0 ng/ml, while 4 mg dexamethasone significantly (p less than 0.05) potentiated GH secretion elicited by GHRH (29.2 +/- 5.7 ng/ml). When dexamethasone 8 mg was given 12 h before, GHRH-induced GH secretion was completely blocked (3.0 +/- 1.1 ng/ml) (p less than 0.05). These results indicate that corticoids have two different actions: an acute potentiating activity on GHRH, and a delayed blocking action on GHRH-induced GH secretion.     

Diagnosis and treatment of acromegaly complications

The Pituitary Society in conjunction with the European Neuroendocrine Association held a consensus workshop to develop guidelines for diagnosis and treatment of the co-morbid complications of acromegaly. Fifty nine pituitary specialists (endocrinologists, neurosurgeons and cardiologists) assessed the current published literature on acromegaly complications in light of recent advances in maintaining tight therapeutic control of GH hypersecretion. The impact of elevated GH levels on cardiovascular disease, hypertension, diabetes, sleep apnea, colon polyps, bone disease, reproductive disorders, and neuropsychologic complications were considered. Guidelines are proposed for effective management of these complications in the context of overall acromegaly control. When appropriate, requirements for prospective evidence-based studies and surveillance database development are enunciated. Effective management of co-morbid acromegaly complications will lead to improved morbidity and mortality in acromegaly.     

Serum leptin levels in acromegalic patients before and during somatostatin analogs therapy

GH excess is characterized by alterations of body composition such as decreased body fat mass; however, scant data are present regarding its effect on serum leptin levels. To better elucidate this topic, leptin secretion was studied in 20 acromegalic patients, before and after 6 months of treatment with somatostatin analogs (SR-lanreotide 30 mg and octreotide LAR). Basal GH, IGF-I, insulin, blood glucose and lipid levels were measured and the area under the curve (AUC) for insulin and glucose and oral glucose insulin sensitivity (OGIS) during oral glucose tolerance test (OGTT) were calculated. After 6 months of somatostatin analogs therapy, a significant reduction in GH and IGF-I plasma levels was observed (p<0.0005, both) with a significant increase of leptin levels (7.4+/-1.3 vs 13.2+/-1.6 ng/ml; p<0.05). Interestingly, the typical correlation of leptin with body mass index (BMI) was not present in active acromegaly, whereas it was restored after somatostatin analogs treatment; moreover, the gender difference in leptin secretion between men and women was preserved in active and controlled acromegaly. In conclusion, the gender-based leptin differences are preserved and leptin secretion/BMI ratio is normalized in acromegalic patients after somatostatin analogs therapy.     

Obesidomics: contribution of adipose tissue secretome analysis to obesity research

Obesity is presently reaching pandemic proportions and it is becoming a major health concern in developed and developing countries due to its comorbidities like type II diabetes, cardiovascular pathologies, and some cancers. The discovery of the adipose tissue role as an endocrine gland able to secrete adipokines that affects whole-body energy homeostasis has become a key break-through toward a better molecular understanding of obesity. Among the known adipokines involved in the regulation of energy metabolism very few have been clearly seen as central regulators of insulin sensitivity, metabolism, and energy homeostasis. Thus, the discovery and characterization of new adipocyte-derived factors is still in progress. Proteomics technology has emerged as a useful tool to analyze adipose tissue secretion (secretome) dynamics giving a wider picture into the molecular events that control body weight. Besides the identification of new secreted proteins, the advantage of using this approach is the possibility to detect post-translational modifications and protein interactions that generally cannot be predicted by genome studies. In this review, we summarize the recent efforts to identify new bioactive adipokines by proteomics especially in pathological situations such as obesity.