Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.

Glenohumeral interposition of rotator cuff stumps: a rare complication of traumatic rotator cuff tear

Abstract The present report describes a case where typical findings of traumatic glenohumeral interposition of rotator cuff stumps were surgically confirmed. This condition is a rare complication of shoulder trauma. Generally, it occurs in high-energy trauma, frequently in association with glenohumeral joint dislocation. Radiography demonstrated increased joint space, internal rotation of the humerus and coracoid process fracture. In addition to the mentioned findings, magnetic resonance imaging showed massive rotator cuff tear with interposition of the supraspinatus, infraspinatus and subscapularis stumps within the glenohumeral joint. Surgical treatment was performed confirming the injury and the rotator cuff stumps interposition. It is important that radiologists and orthopedic surgeons become familiar with this entity which, because of its rarity, might be neglected in cases of shoulder trauma.

Efeitos da inoculação micorrízica e da adubação fosfatada em mudas de Vochysia maxima Ducke

Para verificar os efeitos da inoculação micorrízica e da adubação fosfatada em mudas de Vochysia maxima (quaruba), foi realizado um experimento em casa de vegetação. Testaram-se nove espécies de fungos micorrízicos arbusculares (FMAs): Gigaspora sp., Acaulospora appendicula, Scutellospora heterogama, Acaulospora sp., Scutellospora sp., Gigaspora margarita, Glomus mosseae, Scutellospora gilmorei e Entrophospora colombiana. A inoculação foi feita pela deposição de solos inóculos de FMAs debaixo da radícula das plântulas, durante a repicagem para copos de plástico de 200 ml, contendo Latossolo Amarelo álico fumigado e não-fumigado. Três meses depois, as mudas foram transferidas para vasos de plástico, contendo 2 kg do mesmo solo, com ou sem a incorporação de fósforo (90 mg/dm³ de solo), na forma de superfosfato simples. O estado nutricional e o crescimento das plantas foram avaliados 12 meses depois da inoculação. As mudas desenvolveram pouco sem aplicação de fósforo, tanto no solo fumigado quanto no solo não-fumigado, mesmo inoculando fungos micorrízicos. Com a aplicação de fósforo, um aumento de 76% em produção de matéria seca foi obtido com a inoculação de Glomus mosseae e Gigaspora sp. no solo fumigado e não-fumigado, respectivamente. Essas duas espécies promoveram também a maior quantidade acumulada de fósforo na parte aérea da planta, sendo 71% pelo Glomus mosseae no solo fumigado e 96% pelo Gigaspora sp. no solo não-fumigado, em relação às mudas não-inoculadas, evidenciando alta exigência de quaruba em fósforo. A inoculação e a adubação fosfatada beneficiaram o crescimento e a absorção de P das plantas, mesmo no solo não-fumigado.

Efeito da aplicação de ácido giberélico no crescimento da palmeira-ráfia

A palmeira-ráfia possui grande importância econômica devido ao seu interesse comercial. É uma planta ornamental muito apreciada por sua beleza e utilização em ambiente interno, crescendo bem em locais com sombra e apresentando resistência à exposição solar. O valor econômico dessa planta está relacionado à altura e número de hastes. O objetivo do trabalho foi promover o crescimento da planta, através da aplicação do regulador de crescimento ácido giberélico (GA3). Mudas de palmeira-ráfia com aproximadamente um ano de idade foram aspergidas a cada 21 dias (quatro aplicações) com solução de ácido giberélico nas concentrações de 0; 75; 150; 225; e 300 mg.L-1. Os resultados indicaram que a aplicação do ácido giberélico foi eficiente na promoção do crescimento da espécie, sendo esse incremento significativo nas variáveis: comprimento dos pecíolos, lâminas foliares e altura da planta. Não se observou diferença no acúmulo de matéria seca ou fresca do pecíolo entre os tratamentos, e plantas do tratamento-controle foram superiores às dos tratamentos 225 e 300 mg L-1, nas variáveis diâmetro do colo e massa fresca e seca das raízes. Devido ao incremento na altura das mudas e à alteração da disposição das folhas da palmeira, a utilização do ácido giberélico pode ser recomendada para a produção de mudas de alta qualidade.

Andean indigenous food crops: nutritional value and bioactive compounds

The Andean area of South America is a very important center for the domestication of food crops. This area is the botanical origin of potato, peanut and tomato. Less well- known crops, such as quinoa (Chenopodium quinoa), kañiwa (Chenopodium pallidicaule) and kiwicha (Amaranthus caudatus), were also domesticated by ancient Andean farmers. These crops have a long history of safe use with the local populations and they have contributed to the nutrition and wellbeing of the people for centuries. Several studies have reported the nutritional value of Andean grains. They contain proteins with a balanced essential amino acid composition that are of high biological value, good quality oil and essential minerals, for example iron, calcium and zinc. They are potential sources of bioactive compounds such as polyphenols and dietary fiber. The main objective of the practical work was to assess the nutritional value of Andean native grains with a special emphasis on the bioactive components and the impact of processing. The compounds studied were phenolic acids, flavonoids, betalains and dietary fiber. The radical scavenging activity was measured as well. Iron, calcium and zinc content and their bioavailability were analyzed as well. The grains were processed by extrusion with the aim to study the effect of processing on the chemical composition. Quinoa, kañiwa and kiwicha are very good sources of dietary fiber, especially of insoluble dietary fiber. The phenolic acid content in Andean crops was low compared with common cereals like wheat and rye, but was similar to levels found in oat, barley, corn and rice. The flavonoid content of quinoa and kañiwa was exceptionally high. Kiwicha did not contain quantifiable amounts of these compounds. Only one variety of kiwicha contained low amounts of betalains. These compounds were not detected in kañiwa or quinoa. Quinoa, kañiwa and kiwicha are good sources of minerals. Their calcium, zinc and iron content are higher than the content of these minerals in common cereals. In general, roasting did not affect significantly mineral bioavailability. On the contrary, in cooked grains, there was an increase in bioavailability of zinc and, in the case of kañiwa, also in iron and calcium bioavailability. In all cases, the contents of total and insoluble dietary fiber decreased during the extrusion process. At the same time, the content of soluble dietary fiber increased. The content of total phenolics, phytic acid and the antioxidant activity decreased in kiwicha varieties during the extrusion process. In the case of quinoa, the content of total phenolic compounds and the radical scavenging activity increased during the extrusion process in all varieties. Taken together, the studies presented here demonstrate that the Andean indigenous crops have excellent potential as sources of minerals, flavonoids and dietary fiber. Further studies should be conducted to characterize the phenolic compound and antioxidant composition in processed grains and end products. Quinoa, kañiwa and kiwicha grains are consumed widely in Andean countries but they also have a significant, worldwide potential as a new cultivated crop species and as an imported commodity from South America. Their inclusion in the diet has the potential to improve the intake of minerals and health-promoting bioactive compounds. They may also be interesting raw materials for special dietary foods and functional foods offering natural sources of specific health-promoting components.

The importance of Leptospira interrogans serovars Icterohaemorrhagiae and Canicola in coastal zone and in southern fields of Rio Grande do Sul, Brazil

This study aimed to describe the occurrence of Leptospira interrogans serovars Icterohaemorrhagiae and Canicola, in coastal zone and in southern grasslands of Rio Grande do Sul, Brazil. In each one of the four analyzed farms blood samples were collected from free-living wild animals, domestic animals and humans to perform serological testing for leptospirosis. The presence of antibodies was verified by microscopic agglutination test (MAT). The criterion adopted to consider a serum as agglutination reactant was at least 50% of leptospira for a microscopic field of 100x. From 17 blood samples collected at Chuí, five (29.41%) were positive, three (60.00%) for serovar Icterohaemorrhagiae and two (40.00%) for Canicola. From 21 samples collected in the County of Santana da Boa Vista, six (28.57%) were positive, four (66.67%) for serovar Canicola and two (33.33%) for serovar Icterohaemorrhagiae. From 32 samples collected at Alegrete, 10 (31.25%) were positive, seven (70.00%) for serovar Icterohaemorrhagiae and three (30.00%) foro serovar Canicola. From 17 blood samples collected in Cruz Alta, three (17.64%) were positive, two (66.67%) for serovar Icterohaemorrhagiae and one (33.33%) for Canicola. It is necessary to improve sanitary practices on farms in the state of Rio Grande do Sul, in order to achieve success in leptospirosis control programs.

Velocidade de emergência e crescimento inicial de cultivares de arroz irrigado influenciando a competitividade com as plantas daninhas

A utilização de cultivares de arroz com elevada habilidade competitiva constitui-se numa alternativa para minimizar os efeitos adversos das plantas daninhas sobre a produção das culturas; assim, a rapidez de emergência e a de crescimento inicial são características fisiológicas desejáveis, que aceleram a ocupação do espaço e a utilização dos recursos do meio por um cultivar, reduzindo dessa forma os efeitos competitivos das plantas daninhas. O objetivo deste trabalho foi de investigar variações nas velocidades de emergência e de crescimento inicial de plantas de diferentes cultivares de arroz irrigado. Para isso, foram conduzidos dois experimentos em vasos durante o verão de 1999/2000. Os cultivares avaliados foram: Bluebelle, BR IRGA 410, BRS Chuí, BRS Ligerinho, BRS Taim, CICA 8, EEA 406, El Paso L 144, EPAGRI 108, IAS 12-9 Formosa, IR 841, IRGA 417, IRGA 418, IRGA 421 e XL 6. Avaliou-se a velocidade de emergência até os 10 dias após a semeadura (DAS). A velocidade de crescimento inicial foi caracterizada pelas variáveis área foliar, estádio de desenvolvimento, estatura e fitomassa seca da parte aérea e do sistema radicular, determinadas em duas épocas: aos 14 e 24 DAS. Os cultivares Ligeirinho e IR 841 foram os que mais se destacaram quanto à velocidade de emergência; em contrapartida, os cultivares Formosa e XL 6 demonstraram lenta emergência. Considerando conjuntamente as quatro variáveis relativas ao crescimento inicial de plantas, os cultivares de maior destaque para crescimento inicial mais rápido na primeira avaliação (14 DAS) foram Ligeirinho, El Paso e IRGA 418, enquanto Formosa, Bluebelle e XL 6 foram os de menor crescimento. Na segunda determinação (24 DAS), posicionaram-se em destaque Chuí, El Paso e Ligeirinho, enquanto IR 841 e Formosa apresentaram os piores desempenhos em variáveis de crescimento inicial.

Efeito do frio sobre os carboidratos solúveis em culturas embriogênicas de Acca sellowiana O. Berg (Myrtaceae)

A rota da embriogênese somática de Acca sellowiana, uma espécie arbórea frutífera com limitações quanto à propagação vegetativa, já foi estabelecida mas o número de embriões que restabelecem o crescimento após a fase cotiledonar é baixo. No presente trabalho, embriões somáticos em diferentes fases de desenvolvimento foram obtidos após tratamentos com 2,4-D e submetidos à condição de frio (4 °C) durante 20 dias, visando induzir a transformação de embriões somáticos em plântulas. Observou-se que 95% dos embriões zigóticos desenvolveram embriões somáticos quando tratados com 2,4-D de forma contínua (T1), enquanto que apenas 55% foram formados quando a auxina foi usada na forma pulsada (T2). Porém, o tratamento T1 induziu altas taxas (82%) de deformações nos embriões quando comparados a T2 (62%). Em ambos os tratamentos, não houve formação de plântulas a partir de embriões somáticos após a exposição ao frio, sendo observada redução nos níveis de rafinose. Em T1, 50% dos embriões cultivados na fase globular permaneceram quiescentes e apenas os embriões na fase cotiledonar (76%) apresentaram características positivas de retomada de desenvolvimento, havendo, porém, redução nos teores de açúcares totais com o desenvolvimento e a diferenciação dos embriões. No tratamento T2, apenas 30% dos embriões na fase cotiledonar tornaram-se verdes e apresentaram maiores valores de carboidratos solúveis totais. A análise da composição destes açúcares evidenciou que os componentes majoritários foram myo-inositol, glucose e frutose, no início da cultura e teores decrescentes de sacarose durante o período de cultivo. As baixas concentrações de rafinose durante o período de crescimento e sua redução durante o tratamento a frio, bem como o complexo metabolismo dos carboidratos associado ao uso de reguladores de crescimento podem estar relacionadas com as alterações observadas no desenvolvimento normal dos embriões somáticos, sem haver acúmulo de carboidratos, e inibindo a regeneração das plântulas de Acca sellowiana.

Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a). To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [³H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

Effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity in Chinese subjects: an interventional study

Accumulating evidence has suggested that high salt and potassium might be associated with vascular function. The aim of this study was to investigate the effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity (PWV) in Chinese subjects. Forty-nine subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day NaCl), a high-salt diet for an additional 7 days (18.0 g/day NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day NaCl+4.5 g/day KCl). Brachial-ankle PWV was measured at baseline and on the last day of each intervention. Blood pressure levels were significantly increased from the low-salt to high-salt diet, and decreased from the high-salt diet to high-salt plus potassium supplementation. Baseline brachial-ankle PWV in salt-sensitive subjects was significantly higher than in salt-resistant subjects. There was no significant change in brachial-ankle PWV among the 3 intervention periods in salt-sensitive, salt-resistant, or total subjects. No significant correlations were found between brachial-ankle PWV and 24-h sodium and potassium excretions. Our study indicates that dietary salt intake and potassium supplementation, at least in the short term, had no significant effect on brachial-ankle PWV in Chinese subjects.

Differentiating origins of outflow tract ventricular arrhythmias: a comparison of three different electrocardiographic algorithms

Our objective is to evaluate the accuracy of three algorithms in differentiating the origins of outflow tract ventricular arrhythmias (OTVAs). This study involved 110 consecutive patients with OTVAs for whom a standard 12-lead surface electrocardiogram (ECG) showed typical left bundle branch block morphology with an inferior axis. All the ECG tracings were retrospectively analyzed using the following three recently published ECG algorithms: 1) the transitional zone (TZ) index, 2) the V2 transition ratio, and 3) V2 R wave duration and R/S wave amplitude indices. Considering all patients, the V2 transition ratio had the highest sensitivity (92.3%), while the R wave duration and R/S wave amplitude indices in V2 had the highest specificity (93.9%). The latter finding had a maximal area under the ROC curve of 0.925. In patients with left ventricular (LV) rotation, the V2 transition ratio had the highest sensitivity (94.1%), while the R wave duration and R/S wave amplitude indices in V2 had the highest specificity (87.5%). The former finding had a maximal area under the ROC curve of 0.892. All three published ECG algorithms are effective in differentiating the origin of OTVAs, while the V2 transition ratio, and the V2 R wave duration and R/S wave amplitude indices are the most sensitive and specific algorithms, respectively. Amongst all of the patients, the V2 R wave duration and R/S wave amplitude algorithm had the maximal area under the ROC curve, but in patients with LV rotation the V2 transition ratio algorithm had the maximum area under the ROC curve.

Caracterização do grânulo de amido de bananas (Musa AAA-Nanicão e Musa AAB-Terra)

O amido de bananas tem sido pesquisado na área de nutrição a partir da introdução do conceito de Amido Resistente. O amido de Musa AAA-Nanicão e Musa AAB-Terra foram caracterizados quanto as suas respostas fisiológicas [12]. Em continuidade, o presente trabalho estudou características físicas e morfológicas dos grânulos de amido de ambas as espécies de banana comparando-as com amido nativo de milho comercial. O amido de bananas foi extraído segundo CHIANG, CHU & CHU [3]. A morfologia dos grânulos foi realizada após tratamento enzimático in vitro a 37°C/24h com alfa-amilase pancreática. Foram efetuados os respectivos amilogramas e difractogramas de raios-X. Os grânulos de amido da Musa Tipo AAA-Nanicão apresentaram comprimento entre 30-40µm. Em Musa AAB-Terra, os grânulos, também ovais e alongados, eram um pouco menores, 20-30µm. A corrosão enzimática in vitro iniciava-se sobre a superfície anteriormente lisa e formavam estrias superficiais e apicais. A Microscopia Eletrônica de Varredura (MEV) mostrou que a hidrólise in vitro por 24 horas foi pequena e ocorria sobretudo nas camadas amorfas dos grânulos de ambas as espécies. O padrão de corrosão demonstrou-se distinto daquele ocorrido no amido de milho. As suspensões de amido de bananas ao viscosímetro demonstraram forte capacidade de hidratação e menor capacidade de retrogradação em relação ao milho, sobretudo do amido de Musa Tipo AAA-Nanicão; o amido de Musa Tipo AAB-Terra apresentou maior estabilidade de pasta. Na análise de difração de raios-X, os grânulos de bananas apresentaram padrão tipo B e C para Musa Tipo AAA-Nanicão e Musa Tipo AAB-Terra, respectivamente. Conclui-se que os amidos de Musa AAA-Nanicão e Musa AAB-Terra são estruturalmente distintos, justificando as respostas fisiológicas distintas encontradas posteriormente pelos mesmos autores. As distinções das propriedades físicas e bioquímicas obtidas para os grânulos, embora moderadas entre si e bastante distintas em relação ao amido de milho, não explicaram a alta resistência dos amidos das bananas à digestão enzimática. Os parâmetros obtidos nas análises permitiram, pela primeira vez avaliar as características e diferenças entre grânulos de amido de espécies distintas de banana e suas relações ao amido de milho.