Up-regulation of P2X7 receptor-mediated inhibition of GABA uptake by nerve terminals of the human epileptic neocortex.

OBJECTIVE: Thirty percent of patients with epilepsy are refractory to medication. The majority of these patients have mesial temporal lobe epilepsy (MTLE). This prompts for new pharmacologic targets, like ATP-mediated signaling pathways, since the extracellular levels of the nucleotide dramatically increase during in vitro epileptic seizures. In this study, we investigated whether sodium-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake by isolated nerve terminals of the human neocortex could be modulated by ATP acting via slow-desensitizing P2X7 receptor (P2X7R). METHODS: Modulation of [(3) H]GABA and [(14) C]glutamate uptake by ATP, through activation of P2X7R, was investigated in isolated nerve terminals of the neocortex of cadaveric controls and patients with drug-resistant epilepsy (non-MTLE or MTLE) submitted to surgery. Tissue density and distribution of P2X7R in the human neocortex was assessed by Western blot analysis and immunofluorescence confocal microscopy. RESULTS: The P2X7R agonist, 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-100 µm) decreased [(3) H]GABA and [(14) C]glutamate uptake by nerve terminals of the neocortex of controls and patients with epilepsy. The inhibitory effect of BzATP (100 µm) was prevented by the selective P2X7R antagonist, A-438079 (3 µm). Down-modulation of [(14) C]glutamate uptake by BzATP (100 µm) was roughly similar in controls and patients with epilepsy, but the P2X7R agonist inhibited more effectively [(3) H]GABA uptake in the epileptic tissue. Neocortical nerve terminals of patients with epilepsy express higher amounts of the P2X7R protein than control samples. SIGNIFICANCE: High-frequency cortical activity during epileptic seizures releases huge amounts of ATP, which by acting on low-affinity slowly desensitizing ionotropic P2X7R, leads to down-modulation of neuronal GABA and glutamate uptake. Increased P2X7R expression in neocortical nerve terminals of patients with epilepsy may, under high-frequency firing, endure GABA signaling and increase GABAergic rundown, thereby unbalancing glutamatergic neuroexcitation. This study highlights the relevance of the ATP-sensitive P2X7R as an important negative modulator of GABA and glutamate transport and prompts for novel antiepileptic therapeutic targets.

[Bronchiolitis obliterans organizing pneumonia--experience of a pulmonology ward]. / Bronquiolite obliterante com pneumonia organizada (BOOP)--experiência de um serviço de pneumologia.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a physiopathologic syndrome associating suggestive clinical and imaging features with histopathologic studies showing buds of connective tissue in the lu- men of the distal pulmonary airspace. The aim of the study is a retrospective review of all patients with BOOP diagnosed in the Pulmonology Unit of Coimbra Hospital Centre (CHC) between 2000 and 2005. Eleven cases (6 female and 5 male) with mean age 54.8 years were diagnosed. Ten patients were non-smokers and one was an ex-smoker. The mean duration of symptoms was 62.1 days with the initial symptoms dyspnea (8), cough (7), fever (5) and weight loss (2). Nine patients had been given multiple antibiotics, crackles were heard in 6, fever was detected in 6 and dyspnea in 5. Chest X-ray showed bilateral alveolar opacities in 6, focal consolidation in 3, multiple bilateral nodular opacities in 1 and linear opacities in 1. Lung function, performed in 7 patients, showed a reduction in the diffusion capacity in 5. BAL was performed in 8, and all revealed an increase in the percentage of lymphocytes, with low CD4/CD8 in 4. Diagnosis was obtained by pulmonary biopsy performed by TBLB (7), VATS (2) and TTLB (1). Systemic corticosteroids were given in 9 patients. Evolution was favourable in 10 and one patient died. The authors emphasise the time symptoms took to develop, the failure of multiple antibiotics, agreement between symptoms and imaging with those published in the literature, the increased lymphocytes in the BAL, the usefulness of TBLB and the good response to corticosteroids.

Ibuprofen removal by heterogeneous photocatalysis and ecotoxicological evaluation of the treated solutions.

Emerging contaminants including pharmaceuticals are a class of compounds that are causing great concern due to several environmental problems. Conventional water and wastewater treatments do not achieve high removal efficiencies for many of these drugs. Therefore, the present work investigated the removal of ibuprofen (IBP) by heterogeneous photocatalysis using TiO2 irradiated with artificial UV light or solar radiation. The treated solutions were tested against Daphnia similis and Raphidocelis subcapitata, which are species commonly used as bioindicators of environmental conditions. The results indicated that IBP removal reached 92% after 1 h of treatment using artificial UV and 1000 mg L-1 of TiO2, which was the optimum catalyst concentration in the range studied (20-1000 mg L-1). TOC removal reached up to 78% after 60 min of treatment using TiO2/artificial UV. Ecotoxicological bioassays indicated that the treated solutions had acute effects, with 30% immobilization of D. similis and 40% growth inhibition of R. subcapitata.

[Allergic inflammatory diseases of the upper airways and their impact on asthma--following on from a case report]. / Doenças inflamatórias alérgicas das vias aéreas superiores e suas implicações na asma brônquica--A propósito de um caso clínico.

The authors present a case report of a patient referred to physician for "difficult-to-treat asthma". Clinical evaluation concluded that severe chronic inflammatory upper airway disease was an asthma worsening factor. Patient demonstrated improvement in asthma control, after surgery. In the context of the clinical study, the authors present a review of the most common allergic inflammatory diseases of the upper airways (allergic rhinitis, chronic sinusitis and nasal polyposis) and reflect on their impact on asthma.

Ibuprofen removal by heterogeneous photocatalysis and ecotoxicological evaluation of the treated solutions.

Emerging contaminants including pharmaceuticals are a class of compounds that are causing great concern due to several environmental problems. Conventional water and wastewater treatments do not achieve high removal efficiencies for many of these drugs. Therefore, the present work investigated the removal of ibuprofen (IBP) by heterogeneous photocatalysis using TiO2 irradiated with artificial UV light or solar radiation. The treated solutions were tested against Daphnia similis and Raphidocelis subcapitata, which are species commonly used as bioindicators of environmental conditions. The results indicated that IBP removal reached 92 % after 1 h of treatment using artificial UV and 1000 mg L(-1) of TiO2, which was the optimum catalyst concentration in the range studied (20-1000 mg L(-1)). TOC removal reached up to 78 % after 60 min of treatment using TiO2/artificial UV. Ecotoxicological bioassays indicated that the treated solutions had acute effects, with 30 % immobilization of D. similis and 40 % growth inhibition of R. subcapitata.

Short-term sublethal (sediment and aquatic roots of floating macrophytes) assays with a tropical chironomid based on postexposure feeding and biomarkers.

This study proposes assays with a freshwater chironomid, Chironomus xanthus, distributed over South America, based on subindividual (acetylcholinesterase activity) and individual (survival and postexposure feeding) level endpoints. Sediment and aquatic-rooted floating macrophyte assays were developed, due to the importance of both substrates for toxicant exposure in subtropical/tropical environments. Assays were evaluated under realistic exposure scenarios by simulating a runoff over an agricultural field dosed with deltamethrin. In situ assays were performed within microcosms to discriminate the effects of deltamethrin from those of additional potential stress factors (organism handling and caging, microcosms, use of aquatic roots, and runoff per se). A laboratory sediment assay based on feeding was conducted with samples from the microcosms. In all assays, both sublethal endpoints were responsive to deltamethrin and more sensitive than survival. Survival and feeding were more sensitive in situ than in the laboratory. In the in situ sediment assays, both sublethal endpoints were within a similar range of sensitivity; they were significantly inhibited as of the lowest Decis dose, from approximately 20 to 70%. In situ feeding was more sensitive in the sediment than in the macrophyte assay, where it was inhibited significantly only at the two highest Decis doses (up to approximately 60%). Larval performance was not influenced significantly by any of the other potential stress factors.

Impact of breastfeeding on the intelligence quotient of eight-year-old children.

OBJECTIVE: This study aimed to determine the influence of breastfeeding on the intellectual capacity of children from a cohort in a developing country, with a control for the main confounding factors. METHODS: A prospective cohort study was performed including all infants born in the hospitals of a medium-size city, and a random sample of these newborns was monitored at 30, 90, and 180 days of life, and at age 8 years. Several aspects of breastfeeding were assessed in the follow-up and, at 8 years, general intellectual capacity was assessed through the Raven's Colored Progressive Matrices test. The statistical analyses used Student's t-test, ANOVA, and linear regression and logistics, considering p-values less than 0.05 as statistically significant associations. RESULTS: At age 8 years, 560 children were assessed with Raven's Colored Progressive Matrices test. The average score was 22.56 points, with a standard deviation of 5.93. The difference in the averages found between the breastfed and non-breastfed groups at six months of age was 1.33 (p=0.008). Mother's and child's skin color, social and economic class, maternal education and smoking, and breastfeeding at six months of age (p=0.007) were still associated with the outcome. CONCLUSIONS: Children that were breastfed for six months or more had better performance in the general intellectual assessment, even after adjusting for the main confounding factors.

Permeability of cork to gases.

The permeability of gases through uncompressed cork was investigated. More than 100 samples were assessed from different plank qualities to provide a picture of the permeability distribution. A novel technique based on a mass spectrometer leak detector was used to directly measure the helium flow through the central area of small disks 10 mm in diameter and 2 mm thick. The permeability for nitrogen, oxygen, and other gases was measured by the pressure rise technique. Boiled and nonboiled cork samples from different sections were evaluated. An asymmetric frequency distribution ranging 3 orders of magnitude (roughly from 1 to 1000 µmol/(cm·atm·day)) for selected samples without macroscopic defects was found, having a peak below 100 µmol/(cm·atm·day). Correlation was found between density and permeability: higher density samples tend to show lower permeability. However, boiled cork showed a mean lower permeability despite having a lower density. The transport mechanism of gases through cork was also examined. Calculations suggest that gases permeate uncompressed cork mainly through small channels between cells under a molecular flow regime. The diameter of such channels was estimated to be in the range of 100 nm, in agreement with the plasmodesmata size in the cork cell walls.

Impacto do aleitamento materno no coeficiente de inteligência de crianças de oito anos de idade / Impact of breastfeeding on the intelligence quotient of eight-year-old children

Objetivo: O objetivo deste estudo foi determinar a influencia do aleitamento materno na capacidade intelectual de crianças pertencentes a uma coorte de um país em desenvolvimento, controlando para os principais fatores de confusão. Métodos: Foi realizado um estudo de coorte prospectiva com todos os recém-nascidos nos hospitais de uma cidade de porte médio e acompanhou-se uma amostra aleatória destes aos 30, 90 e 180 dias de vida e aos 8 anos. No acompanhamento foram avaliados diversos aspectos da amamentação e, aos 8 anos, foi realizada avaliação da capacidade intelectual geral aplicando-se o Teste de Raven. As análises estatísticas utilizaram Teste T, ANOVA e regressão linear e logística, considerando como associações estatisticamente significativas aquelas cujo valor de p foi inferior a 0,05. Resultados: Aos 8 anos 560 crianças participaram da avaliação com o Teste de Raven. A média da pontuação das crianças no teste foi de 22,56 pontos com desvio padrão de 5,93. A diferença de médias entre os grupos em aleitamento materno ou não, aos seis meses, foi de 1,33 (p = 0,008). Permaneceram associadas ao desfecho, após regressão linear e logística, a cor materna e da criança, classe socioeconômica, escolaridade e tabagismo maternos e o aleitamento materno aos 6 meses de idade (p = 0,007). Conclusões: As crianças que mamaram por seis meses ou mais tiveram melhor desempenho na avaliação intelectual geral, mesmo após ajuste para os principais fatores de confundimento.

Objective: This study aimed to determine the influence of breastfeeding on the intellectual capacity of children from a cohort in a developing country, with a control for the main confounding factors. Methods: A prospective cohort study was performed including all infants born in the hospitals of a medium-size city, and a random sample of these newborns was monito-red at 30, 90, and 180 days of life, and at age 8 years. Several aspects of breastfeeding were assessed inthe follow-up and, at 8 years, general intellectual capacity was assessed through the Raven's Colored Progressive Matrices test. The statistical analyses used Student's t-test, ANOVA, and linear regression and logistics, considering p-values less than 0.05 as statistically significant associations. Results: At age 8 years, 560 children were assessed with Raven's Colored Progressive Matrices test. The average score was 22.56 points, with a standard deviation of 5.93. The difference inthe averages foundbetweenthe breastfed and non-breastfed groups at six months of age was 1.33 (p = 0.008). Mother's and child's skin color, social and economic class, maternal education and smoking, and breastfeeding at six months of age (p = 0.007) were still associated with the outcome. Conclusions: Children that were breastfed for six months or more had better performance in the general intellectual assessment, even after adjusting for the main confounding factors.

Impacto do aleitamento materno no coeficiente de inteligência de crianças de oito anos de idade / Impact of breastfeeding on the intelligence quotient of eight-year-old children

OBJETIVO: O objetivo deste estudo foi determinar a influência do aleitamento materno na capacidade intelectual de crianças pertencentes a uma coorte de um país em desenvolvimento, controlando para os principais fatores de confusão. MÉTODOS: Foi realizado um estudo de coorte prospectiva com todos os recém-nascidos nos hospitais de uma cidade de porte médio e acompanhou-se uma amostra aleatória destes aos 30, 90 e 180 dias de vida e aos 8 anos. No acompanhamento foram avaliados diversos aspectos da amamentação e, aos 8 anos, foi realizada avaliação da capacidade intelectual geral aplicando-se o Teste de Raven. As análises estatísticas utilizaram Teste T, ANOVA e regressão linear e logística, considerando como associações estatisticamente significativas aquelas cujo valor de p foi inferior a 0,05. RESULTADOS: Aos 8 anos 560 crianças participaram da avaliação com o Teste de Raven. A média da pontuação das crianças no teste foi de 22,56 pontos com desvio padrão de 5,93. A diferença de médias entre os grupos em aleitamento materno ou não, aos seis meses, foi de 1,33 (p = 0,008). Permaneceram associadas ao desfecho, após regressão linear e logística, a cor materna e da criança, classe socioeconômica, escolaridade e tabagismo maternos e o aleitamento materno aos 6 meses de idade (p = 0,007). CONCLUSÕES: As crianças que mamaram por seis meses ou mais tiveram melhor desempenho na avaliação intelectual geral, mesmo após ajuste para os principais fatores de confundimento.

OBJECTIVE: This study aimed to determine the influence of breastfeeding on the intellectual capacity of children from a cohort in a developing country, with a control for the main confounding factors. METHODS: A prospective cohort study was performed including all infants born in the hospitals of a medium-size city, and a random sample of these newborns was monitored at 30, 90, and 180 days of life, and at age 8 years. Several aspects of breastfeeding were assessed in the follow-up and, at 8 years, general intellectual capacity was assessed through the Raven's Colored Progressive Matrices test. The statistical analyses used Student's t-test, ANOVA, and linear regression and logistics, considering p-values less than 0.05 as statistically significant associations. RESULTS: At age 8 years, 560 children were assessed with Raven's Colored Progressive Matrices test. The average score was 22.56 points, with a standard deviation of 5.93. The difference in the averages found between the breastfed and non-breastfed groups at six months of age was 1.33 (p = 0.008). Mother's and child's skin color, social and economic class, maternal education and smoking, and breastfeeding at six months of age (p = 0.007) were still associated with the outcome. CONCLUSIONS: Children that were breastfed for six months or more had better performance in the general intellectual assessment, even after adjusting for the main confounding factors.