DSD Due to 5 alpha-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome

Most of the patients with 5 alpha-RD 2 deficiency are reared in the female social sex due to their severely undervirilized external genitalia but similar to 60% who have not been submitted to orchiectomy in childhood undergo male social sex change at puberty. In our cohort of 30 cases from 18 families, all subjects were registered in the female social sex except for two children-one who had an affected uncle and the other who was diagnosed before being registered. The majority of the patients were satisfied with the long-term results of their treatment and surprisingly, penile length was not associated with satisfactory or unsatisfactory sexual activity. Steroid 5 alpha-RD2 deficiency should be included in the differential diagnosis of all newborns with 46,XY DSD with normal testosterone production before gender assignment or any surgical intervention because these patients should be considered males at birth.

5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

5-lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

Acrodermatitis due to zinc deficiency after combined vertical gastroplasty with jejunoileal bypass: case report

CONTEXT: Nutritional complications may occur after bariatric surgery, due to restriction of food intake and impaired digestion or absorption of nutrients. CASE REPORT: After undergoing vertical gastroplasty and jejunoileal bypass, a female patient presented marked weight loss and protein deficiency. Seven months after the bariatric surgery, she presented dermatological features compatible with acrodermatitis enteropathica, as seen from the plasma zinc levels, which were below the reference values (34.4 mg%). The skin lesions improved significantly after 1,000 mg/day of zinc sulfate supplementation for one week. CONCLUSIONS: The patient's evolution shows that the multidisciplinary team involved in surgical treatment of obesity should take nutritional deficiencies into consideration in the differential diagnosis of skin diseases, in order to institute early treatment.

Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: The Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients

CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.

Nanogravimetric study of lead underpotential deposition on selenium thin films as a semiconductor alloy formation procedure

An electrochemical quartz crystal microbalance Au electrode modified with a Se thin film was used to investigate the electrochemical behavior of lead ad-atoms using underpotential deposition (UPD) conditions. A specific quasi-reversible process was observed during the reduction of Pb2+ on Se thin films in perchloric acid media. The charge density of Pb ad-atoms on Se thin film (46.86 mu C cm(-2)) suggests a recovery of 0.1 monolayers, which is in good agreement with EQCM data. The Se thin film can be successfully alloyed with Pb atoms that are deposited by chronoamperometry using time intervals large enough to allow for diffusion toward the inner Se phase. Linear sweep voltammetry combined with EQCM in perchloric acid was used to characterize the amount of Pb absorbed in the Se thin film. These findings offer a new strategy for alloy formation in semiconductor films using UPD as an effective tool to quantify the exact amount of the incorporated metal.

Glutathione Peroxidase 1 Pro198Leu Polymorphism in Brazilian Alzheimer's Disease Patients: Relations to the Enzyme Activity and to Selenium Status

Background/Aims: Oxidative stress plays a central role in Alzheimer's disease (AD). Pro198Leu cytosolic glutathione peroxidase (GPx1) polymorphism seems to be associated with a lower activity of this enzyme, but there are no studies with AD patients. Thus, the aim was to determine the frequency of the GPx1 Pro198Leu polymorphism in AD patients and to verify its relation to glutathione peroxidase (GPx) activity and selenium (Se) status. Methods:The study was carried out in a group of AD elderly (n = 28) compared to a control group (n = 29). Blood Se concentrations were measured through hydride generation atomic absorption spectroscopy. GPx activity was determined using a commercial kit, and the polymorphism using amplified DNA sequencing. Results:The distribution of genotypes was not different between groups. The variant allele frequency was 0.179 (AD group) and 0.207 (control group). Although no differences regarding GPx activity were found between individuals with different genotypes, lower blood Se levels were found in Pro/Pro AD patients compared to Pro/Pro control subjects, which was not found in the Pro/Leu groups. Moreover, the association between the erythrocyte Se concentration and GPx activity was affected by the Pro198Leu genotype. Conclusions: Results indicate that this polymorphism had apparently affected Se status in AD patients and that more studies in this field are necessary. Copyright (c) 2012 S. Karger AG, Basel

No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon

Selenium (Se) is an essential element and a well-known anti-oxidant. In the Lower Tapajos River region of the Brazilian Amazon, biomarkers of Se range from normal to very high. The local traditional diet includes important Se sources such as Brazil nuts, chicken, game meat and certain fish species. Some studies have reported alterations in keratin structure, gastrointestinal problems and paresthesia in populations with high Se intake. The objective of the present study was to evaluate cutaneous and garlic odor of the breath signs and sentinel symptoms of Se toxicity (selenosis) in relation to Se status in communities along the Tapajos River. Participants (N = 448), aged 15-87 years, were recruited from 12 communities. Se concentrations were measured in blood (B-Se) and plasma (P-Se) by ICP-MS. A nurse performed an examination of the hair, nails, skin and breath for signs of Se toxicity. Interview-administered questionnaires were used to collect information on socio-demographics, medical history and possible symptoms of Se toxicity. In this population, the median levels of B-Se and P-Se were 228.4 mu g/L (range 103.3-1500.2 mu g/L) and 134.8 mu g/L (range 53.6-913.2 mu g/L) respectively. Although B-Se and P-Se surpassed concentrations considered toxic (B-Se: 1000 mu g/L (U.S. EPA, 2002)), no dermal or breath signs or symptoms of Se toxicity were associated with the biomarkers of Se status. In the present study population, where Se intake is mostly from traditional diet, there is no evidence of selenosis. These findings support the need to re-assess Se toxicity considering factors such as the chemical form of Se exposure, route of exposure (inhaled versus ingested), co-exposures to toxic elements such as mercury. Considering the current food transition towards a western diet in the Amazon, further studies should address the possible association between high Se status and cardiometabolic health in this study population. (C) 2011 Elsevier Ltd. All rights reserved.

Growth hormone pharmacogenetics: the interactive effect of a microsatellite in the IGF1 promoter region with the GHR-exon 3 and-202 A/C IGFBP3 variants on treatment outcomes of children with severe GH deficiency

Insulin-like growth factor type 1 (IGF1) is a mediator of growth hormone (GH) action, and therefore, IGF1 is a candidate gene for recombinant human GH (rhGH) pharmacogenetics. Lower serum IGF1 levels were found in adults homozygous for 19 cytosine-adenosine (CA) repeats in the IGF1 promoter. The aim of this study was to evaluate the influence of (CA)n IGF1 polymorphism, alone or in combination with GH receptor (GHR)-exon 3 and -202 A/C insulin-like growth factor binding protein-3 (IGFBP3) polymorphisms, on the growth response to rhGH therapy in GH-deficient (GHD) patients. Eighty-four severe GHD patients were genotyped for (CA) n IGF1, -202 A/C IGFBP3 and GHR-exon 3 polymorphisms. Multiple linear regressions were performed to estimate the effect of each genotype, after adjustment for other influential factors. We assessed the influence of genotypes on the first year growth velocity (1st y GV) (n = 84) and adult height standard deviation score (SDS) adjusted for target-height SDS (AH-TH SDS) after rhGH therapy (n = 37). Homozygosity for the IGF1 19CA repeat allele was negatively correlated with 1st y GV (P = 0.03) and AH-TH SDS (P = 0.002) in multiple linear regression analysis. In conjunction with clinical factors, IGF1 and IGFBP3 genotypes explain 29% of the 1st y GV variability, whereas IGF1 and GHR polymorphisms explain 59% of final height-target-height SDS variability. We conclude that homozygosity for IGF1 (CA) 19 allele is associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with severe GHD. Furthermore, this polymorphism exhibits a non-additive interaction with -202 A/C IGFBP3 genotype on the 1st y GV and with GHR-exon 3 genotype on adult height. The Pharmacogenomics Journal (2012) 12, 439-445; doi:10.1038/tpj.2011.13; published online 5 April 2011

Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency

We describe a novel chromosome microdeletion at 15q26.1 detected by oligo-array-CGH in a 6-year-old girl presenting with global development delay, epilepsy, autistic behavior and facial dysmorphisms. Although these features are often present in Angelman syndrome, no alterations were present in the methylation pattern of the Prader-Willi-Angelman critical region. The deletion encompasses only 2 genes: CHD2, which is part of a gene family already involved in CHARGE syndrome, and RGMA which exerts a negative control on axon growth. Deletion of either or both genes could cause the phenotype of this patient. These results provide a further chromosome region requiring evaluation in patients presenting Angelman features. (C) 2011 Elsevier Masson SAS. All rights reserved.

Evidence of zinc deficiency in competitive swimmers

Objective: The aim of this study was to assess the nutritional zinc (Zn) status of elite swimmers during different training periods. Methods: A longitudinal paired study was performed at the University of Sao Paulo in eight male swimmers 18 to 25 y old who had been swimming competitively at the state and national levels for at least 5 y. The swimmers were evaluated over a total period of 14 wk: before the basic and specific preparatory period (BSPP-baseline), at the end of the basic and specific preparatory period (post-BSPP), and at the end of the polishing period (PP). Levels of Zn were determined in the plasma, erythrocyte, urine, and saliva by atomic absorption spectrophotometry. Anthropometric measurements and a 3-d food record were also evaluated. Results: The median plasma Zn concentration was below the reference value in all training periods (BSPP-baseline 59 mu g/dL, post-BSPP 55.9 mu g/dL, after PP 58.8 mu g/dL, P > 0.05), as were threshold values for erythrocytes (BSPP-baseline 36.5 mu g of Zn/g of hemoglobin, post-BSPP 42 mu g of Zn/g of hemoglobin, after PP 40.7 mu g of Zn/g of hemoglobin, P > 0.05), urinary Zn (BSPP-baseline 280 mu g/24 h, post-BSPP 337 mu g/24 h, after PP 284 mu g/24 h, P > 0.05), and salivary Zn (BSPP-baseline 66.1 mu g/L, post-BSPP 54.1 mu g/L, after PP 79.7 mu g/L, > 0.05). Salivary Zn did not correlate with plasma and erythrocyte Zn levels. Conclusion: The results suggest that the elite swimmers studied presented a possible Zn deficiency and that salivary Zn was not adequate to evaluate the Zn nutritional status. (C) 2012 Elsevier Inc. All rights reserved.

Organic and inorganic sources of zinc, copper and selenium in diets for dairy cows: intake, blood metabolic profile, milk yield and composition

The present study was carried out with the objective of evaluating the effects of feeding dairy cows with organic or inorganic sources of zinc (Zn), copper (Cu) and selenium (Se) on blood concentrations of these minerals, blood metabolic profiles, nutrient intake and milk yield and composition. Nineteen Holstein cows were selected and randomly assigned to two groups for receiving organic (n = 9) or inorganic (n = 10) sources of Zn, Cu and Se from 60 days before the expected date of calving to 80 days of lactation. Samples of feed, orts and milk were collected for analysis. Body condition score (BCS) was determined and blood samples were collected for analysis of Zn, Cu and Se concentrations, as well as for metabolic profile. Supplying organic or inorganic sources of Zn, Cu, and Se did not affect dry matter and nutrient intake, blood metabolic profile, milk yield and composition, plasma concentration of these minerals, and BCS or change the BCS in cows from 60 days before the expected date of calving to 80 days of lactation. An effect of time was observed on all feed intake variables, plasma concentrations of Zn and Se, milk yield, milk protein content, BCS and change in BCS.

Enrichment of Pleurotus ostreatus mushrooms with selenium in coffee husks

Pleurotus ostreatus fungus forms an edible mushroom that possesses important nutritional and medicinal properties. Selenium (Se) is essential to human diets and it is in low concentration in the soil, and consequently in food. P. ostreatus was grown in coffee husks enriched with various concentrations of sodium selenite. The biological efficiency of P. ostreatus was affected by the addition of high concentrations of Se. The highest level of Se absorption was obtained by adding 51 mg kg(1) of sodium selenite. The mushrooms from first flush contained more Se than the further flushes. These results demonstrate the great potential of coffee husks in the production of Se-enriched mushrooms and show the ability of this fungus to absorb and biomagnify Se. (C) 2011 Elsevier Ltd. All rights reserved.

Patient with toxoplasmosis and glucose-6-phosphate dehydrogenase deficiency: a case report

Abstract Introduction Toxoplasmosis, a zoonotic protozoal disease caused by toxoplasma gondii, is prevalent throughout the world, affecting a large proportion of persons who usually have no symptoms. Glucose 6 phosphate dehydrogenase deficiency, an X-linked inherited disorder, is present in over 400 million people world wide. It is more common in tropical and subtropical countries and is one of the important causes of hemolytic anemia. Case presentation This case report relates the occurrence of the two diseases simultaneously in a child of five years old. Conclusion Patients with glucose-6-phosphate dehydrogenase deficiency are more susceptible to toxoplasmosis and this case report, reinforce the findings of this propensity and alert us for such possibility, what it is important, therefore, the treatment of toxoplasmosis can cause serious hemolysis in these patients.

Deficiency symptoms and uptake of micronutrients by castor bean grown in nutrient solution

Castor bean is a nutrient-demanding species, but there is still little information on its micronutrient requirements. The objectives of this study were to evaluate the effects of levels of B (2.5, 12.5 and 25.0 µmol L-1), Cu (0.05, 0.25 and 0.50 µmol L-1), Mn (0.2, 1.0 and 2.0 µmol L-1) and Zn (0.2, 1.0 and 2.0 µmol L-1) in a nutrient solution on plant B, Cu, Mn and Zn concentrations and uptake, vegetative growth and fruit yield of castor bean "Iris", grown in greenhouse. The experiment was arranged in a completely randomized block design with three replicates. The first deficiency symptoms were observed for B, followed by Zn, Cu and Mn. The main changes in the cell ultrastructure due to lack of B were thickening of the cell walls and middle lamellae, distorted chloroplasts and tightly stacked thylakoids, besides the absence of starch grains. The Mn, Zn and Cu deficiencies led to disruption of chloroplasts, disintegration of thylakoids and absence of amyloplasts. The concentration and uptake of B, Cu, Mn, and Zn in castor bean plants increased with micronutrient supply in the solution. Fruit yield was drastically reduced by B and Mn deficiencies. On the other hand, the dry matter yield of the shoot and root of castor bean plants was not. In the treatment with full nutrient solution, the leaves accumulated 56 and 48 % of the total B and Mn taken up by the plants, respectively, and the seeds and roots 85 and 61 % of the total Cu and Zn taken up, respectively. This shows the high demand of castor bean Iris for B and Mn for fruit yield.

Effects of in vitro selenium supplementation on blood and milk neutrophils from dairy cows

The study was designed to assess the effects of in vitro selenium addition on intracellular hydrogen peroxide production by neutrophils from the milk and blood of dairy cows. Blood from 10 dairy cows and 20 milk samples from five dairy cows were incubated with 0 mg (control) or 10μM of sodium selenite. Then, milk and blood neutrophils were submitted for evaluation of intracellular hydrogen peroxide production by flow cytometry using 2',7'-dichlorofluorescein diacetate as a probe. The selenium status of the animals was evaluated by determination of the blood glutathione peroxidase activity. The results of the present work showed that in vitro selenium supplementation leads to an enhancement in intracellular hydrogen peroxide production, which indicates an improvement in the bactericidal effects of blood and milk neutrophils even in cows with a selenium-adequate status. Thus, the present study showed that in vitro Se supplementation leads to an enhancement in intracellular hydrogen peroxide production, indicating an improvement in the bactericidal effects of blood and milk neutrophils in cows with Se-adequate status.