The Impact of a Natural Olive-Derived Phytocomplex (OliPhenolia®) on Exercise-Induced Oxidative Stress in Healthy Adults.

The role of natural polyphenols in reducing oxidative stress and/or supporting antioxidant mechanisms, particularly relating to exercise, is of high interest. The aim of this study was to investigate OliPhenolia® (OliP), a biodynamic and organic olive fruit water phytocomplex, rich in hydroxytyrosol (HT), for the first time within an exercise domain. HT bioavailability from OliP was assessed in fifteen healthy volunteers in a randomized, double-blind, placebo controlled cross-over design (age: 30 ± 2 yrs; body mass: 76.7 ± 3.9 kg; height: 1.77 ± 0.02 m), followed by a separate randomized, double-blinded, cohort trial investigating the short-term impact of OliP consumption (2 × 28 mL∙d−1 of OliP or placebo (PL) for 16-days) on markers of oxidative stress in twenty-nine recreationally active participants (42 ± 2 yrs; 71.1 ± 2.1 kg; 1.76 ± 0.02 m). In response to a single 28 mL OliP bolus, plasma HT peaked at 1 h (38.31 ± 4.76 ng∙mL−1), remaining significantly elevated (p < 0.001) until 4 h. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and HT were assessed at rest and immediately following exercise (50 min at ~75% V˙O2max then 10 min intermittent efforts) and at 1 and 24 h post-exercise, before and after the 16-day supplementation protocol. Plasma HT under resting conditions was not detected pre-intervention, but increased to 6.3 ± 1.6 ng·mL−1 following OliP only (p < 0.001). OliP demonstrated modest antioxidant effects based on reduced SOD activity post-exercise (p = 0.016) and at 24 h (p ≤ 0.046), and increased GSH immediately post-exercise (p = 0.009) compared with PL. No differences were reported for MDA and CAT activity in response to the exercise protocol between conditions. The phenolic compounds within OliP, including HT, may have specific antioxidant benefits supporting acute exercise recovery. Further research is warranted to explore the impact of OliP following longer-term exercise training, and clinical domains pertinent to reduced oxidative stress.

Assessing the impact of a mushroom-derived food ingredient on vitamin D levels in healthy volunteers.

BACKGROUND: Prevalence of vitamin D insufficiency/deficiency has been noted in athletic populations, although less is known about recreationally active individuals. Biofortification of natural food sources (e.g. UV radiated mushrooms) may support vitamin D status and is therefore of current scientific and commercial interest. The aim of this study was to assess the impact of a mushroom-derived food ingredient on vitamin D status in recreationally active, healthy volunteers. METHODS: Twenty-eight participants were randomly assigned to either: 25 µg (1000 IU) encapsulated natural mushroom-derived vitamin D2; matched-dose encapsulated vitamin D3 or placebo (PL) for 12 weeks. Venous blood samples were collected at baseline, week 6 and 12 for analysis of serum 25(OH)D2 and 25(OH)D3 using liquid chromatography mass spectrometry. Habitual dietary intake and activity were monitored across the intervention. RESULTS: Vitamin D status (25(OH)DTOTAL) was significantly increased with vitamin D3 supplementation from 46.1 ± 5.3 nmol·L- 1 to 88.0 ± 8.6 nmol·L- 1 (p < 0.0001) across the intervention, coupled with an expected rise in 25(OH)D3 concentrations from 38.8 ± 5.2 nmol·L- 1 to 82.0 ± 7.9 nmol·L- 1 (p < 0.0001). In contrast, D2 supplementation increased 25(OH)D2 by + 347% (7.0 ± 1.1 nmol·L- 1 to 31.4 ± 2.1 nmol·L- 1, p < 0.0001), but resulted in a - 42% reduction in 25(OH)D3 by week 6 (p = 0.001). A net + 14% increase in 25(OH)DTOTAL was established with D2 supplementation by week 12 (p > 0.05), which was not statistically different to D3. Vitamin D status was maintained with PL, following an initial - 15% reduction by week 6 (p ≤ 0.046 compared to both supplement groups). CONCLUSIONS: The use of a UV radiated mushroom food ingredient was effective in maintaining 25(OH)DTOTAL in healthy, recreationally active volunteers. This may offer an adjunct strategy in supporting vitamin D intake. However, consistent with the literature, the use of vitamin D3 supplementation likely offers benefits when acute elevation in vitamin D status is warranted.

Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants: Results From the HPTN 040/PACTG 1043 Trial.

BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial. METHODS: Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission. RESULTS: Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6-63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤-2, and 22% with height for Z score ≤-2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5-15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01-2.9) and birth weight-for-age Z score ≤-2 (AOR, 5.2; 95% CI, 1.8-14.8). CONCLUSIONS: There were high rates of undernutrition, stunting and infectious serious adverse effect in this study's formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.

Retinoic acid regulates avian lung branching through a molecular network.

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rarα, and rarß) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgfß2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rarß, meis2, hoxb5, tgfß2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgfß2, and id2 spatial distribution; to increase rarß, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal-distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.

Ethnobotany and popular culture in the use of plants in settlements on the southern edge of southern Pantanal Mato Grosso / Etnobôtanica e a cultura popular no uso de plantas em assentamentos na borda sul do pantanal sul-mato-grossense

Popular culture and its relationship with plants has been the subject of scientific studies and brought significant contributions to science. In this assessment, developed in two settlements in Corumbá and Ladário, Mato Grosso do Sul, was evaluated the use of plants for medicinal purposes. A structured questionnaire was administered to 10 raizeiros, residents of the area, asking which plants were used by them, their methods of preparation and therapeutic indications. Fifty-five plants from 28 families were catalogued among plants native to the region and of exotic and/or external origin, only 40% were native. The predominant form of use is tea (41 citations), followed by infusion (16 citations). The most used parts are the leaves, with 43 citations, followed by flowers (6 citations). There is a predominance of the type of problem for which the plant is used, with 12 citations for problems in the respiratory system, followed by eight for kidney and liver problems and seven for the stomach. What has been found is a wide diversity of species used for the most different problems, indicating the importance of the use of medicinal plants for the communities studied.

A cultura popular e sua relação com as plantas tem sido objeto de estudos científicos e trazido contribuições significativas para a ciência. Nesta pesquisa desenvolvida em dois assentamentos nos municípios de Corumbá e Ladário, Mato Grosso do Sul, foi avaliada a utilização de plantas para fins medicinais. Um questionário estruturado foi aplicado a 10 raizeiros, residentes nos locais, buscando identificar quais plantas eram utilizadas, seus métodos de preparação e indicações terapêuticas. Foram catalogadas 55 plantas de 28 famílias, entre nativas da região e exóticas e/ou de origem externa, sendo que apenas 40% eram nativas. A forma de uso predominante é o chá (41 citações), seguida por infusão (16 citações). As partes mais utilizadas são as folhas, com 43 citações, seguida pelas flores (16 citações). Há uma predominância quanto ao tipo de problema para qual a planta é usada, com 12 citações para problemas no sistema respiratório, seguido por oito para problemas renais e hepáticos e sete relacionadas ao estômago. Verificou-se uma ampla diversidade de espécies utilizadas, para os mais diferentes problemas, indicando a importância da utilização das plantas medicinais para as comunidades estudadas.

Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development.

KEY POINTS: Retinoic acid (RA) and ghrelin levels are altered in human hypoplastic lungs when compared to healthy lungs. Although considerable data have been obtained about RA, ghrelin and bombesin in the congenital diaphragmatic hernia (CDH) rat model, neuroendocrine factors have never been associated with the RA signalling pathway in this animal model. In this study, the interaction between neuroendocrine factors and RA was explored in the CDH rat model. The authors found that normal fetal lung explants treated with RA, bombesin and ghrelin showed an increase in lung growth. Hypoplastic lungs presented higher expression levels of the RA receptors α and γ. Moreover bombesin and ghrelin supplementation, in vitro, to normal lungs increased RA receptor α/γ expression whereas administration of bombesin and ghrelin antagonists to normal and hypoplastic lungs decreased it. These data reveal for the first time that there is a link between neuroendocrine factors and RA, and that neuroendocrine factors sensitise the lung to the RA action through RA receptor modulation. ABSTRACT: Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, ß and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.

Deficiência de IgA associada a Artrite reumatoide juvenil / IgA deficiency and Juvenile rheumatoid arthritis

Objetivo: descrever um caso de deficiência de IgA associado a artrite reumatoide juvenil e infecções de repetição.Relato do caso: paciente de 12 anos, sexo feminino, com diagnóstico de artrite reumatoide juvenil associada a infecção pulmonar grave. A deficiência de IgA foi suspeitada e o diagnósticoconfirmado através da dosagem de IgA sérica.Conclusão: os médicos devem estar atentos ao diagnóstico de deficiência de IgA pela grande associação não só com processos infecciosos e alérgicos, mas, também com doenças auto imunes.

Objective: to describe a case of IgA deficiency and juvenile rheumatoid arthritis and recurrent infections.Case report: a 12 year-old patient, female, diagnosed with juvenile rheumatoid arthritis associated with severe lung infection. IgA deficiency was suspected and the diagnosis was confirmed through serum IgA measurement.Conclusion: physicians should be aware of the diagnosis of IgA deficiency no only beca use of its close association with infectious and allergic processes, but also with auto immune diseases.

Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway.

The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various proinflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as the pattern of proinflammatory cytokine gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during 3 wk an injection of saline, vehicle (zinc plus carboxymethyl cellulose), or thymulin (100 ng/kg, sc, daily). At d 23-25, the animals were anesthetized for hemodynamic recordings, whereas heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin's vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.

Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha.

Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. Recent in vivo studies have shown that hepcidin is down-regulated by erythropoiesis, anemia, and hypoxia, which meets the need of iron input for erythrocyte production. Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin regulation can be hypothesized. We report here the regulation of hepcidin expression by EPO, in a dose-dependent manner, in freshly isolated mouse hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated through EPOR signaling, since hepcidin mRNA levels are restored by pretreatment with an EPOR-blocking antibody. The transcription factor C/EBPalpha showed a pattern of expression similar to hepcidin, at the mRNA and protein levels, following EPO and anti-EPOR treatments. Chromatin immunoprecipitation experiments showed a significant decrease of C/EBPalpha binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO.

Antenatal vitamin A administration attenuates lung hypoplasia by interfering with early instead of late determinants of lung underdevelopment in congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Early and late lung underdevelopment in congenital diaphragmatic hernia (CDH) is likely caused by nonmechanical (directly mediated by nitrofen) and mechanical (mediated by thoracic herniation) factors, respectively. The authors investigated if vitamin A enhances lung growth because of effects on both early and late determinants of lung hypoplasia. METHODS: Twenty-seven pregnant Wistar rats were exposed on embryonic day (E)9.5 to 100 mg of nitrofen or just olive oil. From nitrofen-exposed pregnant rats, 12 were treated at day 9.5 or 18.5 with 15,000 IU of vitamin A. Lungs were harvested at E18, E20, and E22, weighed, and analyzed for DNA and protein contents. Left and/or right lung hypoplasia was estimated by assessment of the ratios of lung to body weight and left to right lung weight. Fetuses were assigned to 5 experimental groups: baseline (exposed neither to nitrofen nor vitamin A), nitrofen (exposed to nitrofen without CDH), CDH (exposed to nitrofen with CDH), nitr+vitA (exposed to nitrofen without CDH and treated with vitamin A), and CDH+vitA (exposed to nitrofen with CDH and treated with vitamin A). RESULTS: Incidence of hernia was significantly reduced in fetuses treated with vitamin A. When vitamin A was administered at E9.5, the authors observed similar effect on lung hypoplasia measured through ratio of lung to body weight at E18 in the nitrofen and CDH groups (nitrofen 1.92% +/- 0.05%, CDH 1.92% +/- 0.04%), whereas lung hypoplasia was attenuated relative to baseline (2.45% +/- 0.05%) in 5% and 4% in nitrofen (nitr+vitA 2.05% +/- 0.03%) and CDH (CDH+vitA 2.08% +/- 0.04%) groups, respectively. At E20, lung hypoplasia was increased in CDH compared with nitrofen groups (nitrofen 2.52% +/- 0.1%, CDH 2.39% +/- 0.05%), whereas vitamin A attenuated lung hypoplasia, in relation to baseline (3.20% +/- 0.07%), 14% in both nitrofen-exposed groups (nitr+vitA 2.96% +/- 0.03%, CDH+vitA 2.83% +/- 0.03%). At E22, lung hypoplasia was significantly higher in CDH group than nitrofen group (nitrofen 2.13% +/- 0.06%, CDH 1.48% +/- 0.03%), whereas lung hypoplasia was attenuated in 9% of both nitrofen-exposed groups (nitr+vitA 2.35% +/- 0.06%, CDH+vitA 1.69% +/- 0.05%) in relation to baseline group (2.38% +/- 0.04%). Administration of vitamin A at E18.5 produced no significant effects on lung growth. CONCLUSIONS: The authors conclude from these results that antenatal administration of vitamin A attenuates lung hypoplasia in CDH by interfering with early determinants of lung underdevelopment. This finding may have clinical implications because prenatal diagnosis of human CDH commonly occurs after 16 weeks' gestation when late determinants of lung hypoplasia likely predominate.

Identification of mutations of Bruton's tyrosine kinase gene (BTK) in Brazilian patients with X-linked agammaglobulinemia.

Mutations in the Bruton tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in the peripheral blood. We evaluated 17 male Brazilian patients from 13 unrelated families who showed markedly reduced numbers of blood B cells and hypogammaglobulinemia. BTK gene analysis detected mutations in 10 of the 13 presumed XLA families. Seven mutations (Q196X, G613D, R28L, 251-273del, Q234X, H364P, and R13X) had been reported previously, whereas the remaining three mutations (M501T, IVS15+1G>C, and IVS14+1G>A) were novel. Mutation IVS15+1G>C occurred in a splice donor site and caused exons 15 and 16 to be skipped, and IVS14+1G>A might cause exon 14 to be skipped. Flow cytometry revealed deficient expression of BTK protein in 10 of the 13 families. This is the first report of the diagnosis of XLA by analysis of mutations of the BTK gene in Brazilian patients.