Assessment of vitamin D status and parathyroid hormone during a combined intervention for the treatment of childhood obesity

Background: Obesity is associated with vitamin D deficiency. The aim of this work is to analyze the changes in vitamin D status and PTH levels in a group of children with obesity receiving combined intervention program in order to get BMI status reduction. Methods: Longitudinal study in 119 children with obesity, aged 9.1–13.9 years, included in a 1-year combined dietarybehavioral-physical activity intervention. Anthropometric measurements (weight, height, BMI and fat mass index) were registered every 3 months and blood testing (calcium, phosphorous, 25(OH)D and PTH) were collected at the beginning and after 12 months of follow-up. A control group was recruited (300 healthy children, aged 8.1–13.9 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. Results: Vitamin D deficiency was significantly higher in obesity group (31.1 vs. 14%). There was negative correlation between 25(OH)D and fat mass index (r = −0.361, p = 0.001). Patients with BMI reduction throughout combined intervention were 52 (43.7%). There was a significant increase in the prevalence of hypovitaminosis D in patients without BMI reduction at the end of follow-up, but in those patients with BMI reduction there was no changes of vitamin D status. Conclusions: Obesity increases the prevalence of suboptimal vitamin D status, and a BMI status reduction in children with obesity may be required to at least stabilize vitamin D status

New 1-aryl-3-substituted propanol derivatives as antimalarial agents

This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 μM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria

Effects of the application of a prolonged combined intervention on body composition in adolescents with obesity

Background: The aim of this study is to describe the effects of a prolonged dietary-behavioral-physical activity intervention (24 months) on body composition in a group of adolescents with obesity. Methods: Longitudinal study in 196 individuals with obesity (86 boys and 110 girls) aged 10.1–14.9 years that completed a prolonged combined intervention (24 months). Values for weight, height, skinfold thickness, waist circumference, BMI, body fat, fat mass index (FMI) and fat-free mass index (FFMI) were registered or calculated. A good response to treatment was reported when a BMI z-score reduction of greater than or equal to 0.5 units of the initial value occurred after 24 month of follow up. Results: A good response after 24 months of follow-up reached 58.2% (n = 114). In boys with obesity and BMI status improvement, weight z-score, BMI z-score, body fat, and FMI significantly decreased (p < 0.05). In girls with obesity and BMI status improvement, weight z-score, BMI z-score, waist circumference, waist z-score, body fat and FMI significantly decreased (p < 0.05). In both sexes the height and FFMI increased significantly (p < 0.05). The multiple logistic regression analysis showed that girls and younger age were associated with BMI status improvement; concurrently, the place of residence (urban or rural) and degree of obesity were not associated with BMI status improvement. Conclusion: The application of long-term combined strategies in the treatment of childhood obesity seems to be effective. As BMI decreases, a reduction in fat mass is also detected, with evident sexual dimorphism, in the absence of changes in fat-free mass and, consequently, in longitudinal growing

What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

[Primary trimethylaminuria or fish odor syndrome. A novel mutation in the first documented case in Spain]

BACKGROUND AND OBJECTIVE: Trimethylaminuria or fish odor syndrome is a metabolic disorder characterized by a failure in the oxidation route from trimethylamine (TMA) to trimethylamineN-oxide (TMA-O). Primary trimethylaminuria is an inherited autosomic recessive disease due to mutations in the human FMO3 gene. High levels of free TMA in urine and other body fluids confer an unpleasant body odor resembling that of fish. Here we report a case of primary trimethylaminuria in a 4-year-old girl. PATIENT AND METHOD: A 4-year-old girl who presented with a strong corporal scent resembling that of fish from the age of 9 months agreeing with the introduction of fish in the diet. The patient did not have other relevant personal history and had a correct psychomotor and growing development. Liver function, urea and creatinine levels were normal. The biochemical diagnosis was done by spectrometry, measuring the amount of TMA and TMA-O prior to and after fish intake. RESULTS: Genetic analysis evinced that the patient was homozygous for a novel mutation in exon 3, R51G (c. 151A > G). Both parents were heterozygous. CONCLUSIONS: R51G (c. 151 A > G) mutation had not been found in other patients with trimethylaminuria

Assessment of vitamin D status and parathyroid hormone during a combined intervention for the treatment of childhood obesity

Background: Obesity is associated with vitamin D deficiency. The aim of this work is to analyze the changes in vitamin D status and PTH levels in a group of children with obesity receiving combined intervention program in order to get BMI status reduction. Methods: Longitudinal study in 119 children with obesity, aged 9.1–13.9 years, included in a 1-year combined dietarybehavioral-physical activity intervention. Anthropometric measurements (weight, height, BMI and fat mass index) were registered every 3 months and blood testing (calcium, phosphorous, 25(OH)D and PTH) were collected at the beginning and after 12 months of follow-up. A control group was recruited (300 healthy children, aged 8.1–13.9 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. Results: Vitamin D deficiency was significantly higher in obesity group (31.1 vs. 14%). There was negative correlation between 25(OH)D and fat mass index (r = −0.361, p = 0.001). Patients with BMI reduction throughout combined intervention were 52 (43.7%). There was a significant increase in the prevalence of hypovitaminosis D in patients without BMI reduction at the end of follow-up, but in those patients with BMI reduction there was no changes of vitamin D status. Conclusions: Obesity increases the prevalence of suboptimal vitamin D status, and a BMI status reduction in children with obesity may be required to at least stabilize vitamin D status

Effects of the application of a prolonged combined intervention on body composition in adolescents with obesity

Background: The aim of this study is to describe the effects of a prolonged dietary-behavioral-physical activity intervention (24 months) on body composition in a group of adolescents with obesity. Methods: Longitudinal study in 196 individuals with obesity (86 boys and 110 girls) aged 10.1–14.9 years that completed a prolonged combined intervention (24 months). Values for weight, height, skinfold thickness, waist circumference, BMI, body fat, fat mass index (FMI) and fat-free mass index (FFMI) were registered or calculated. A good response to treatment was reported when a BMI z-score reduction of greater than or equal to 0.5 units of the initial value occurred after 24 month of follow up. Results: A good response after 24 months of follow-up reached 58.2% (n = 114). In boys with obesity and BMI status improvement, weight z-score, BMI z-score, body fat, and FMI significantly decreased (p < 0.05). In girls with obesity and BMI status improvement, weight z-score, BMI z-score, waist circumference, waist z-score, body fat and FMI significantly decreased (p < 0.05). In both sexes the height and FFMI increased significantly (p < 0.05). The multiple logistic regression analysis showed that girls and younger age were associated with BMI status improvement; concurrently, the place of residence (urban or rural) and degree of obesity were not associated with BMI status improvement. Conclusion: The application of long-term combined strategies in the treatment of childhood obesity seems to be effective. As BMI decreases, a reduction in fat mass is also detected, with evident sexual dimorphism, in the absence of changes in fat-free mass and, consequently, in longitudinal growing

Novel Benzo[b]thiophene Derivatives as New Potential Antidepressants with Rapid Onset of Action

We report benzo[b]thiophene derivatives synthesized according to a dual strategy. 8j, 9c, and 9e with affinity values toward 5-HT7R and 5-HTT were selected to probe using the forced swimming text (FST). The results showed significant antidepressant activity after chronic treatment. 9c was effective in reducing the immobility time in FST even after acute treatment. These findings identify these compounds as a new class of antidepressants with a rapid onset of action