Phenotypic and biochemical responses of sugarcane cultivars to glyphosate application

Sugarcane cultivars show varying degrees of herbicide susceptibility, with herbicide effects ranging from no injury to total plant eradication. In this study, phenotypic and biochemical responses to glyphosate were evaluated in three sugarcane cultivars. Herbicide tolerance of the three cultivars (IACSP93-3046, IACSP94-4004 and RB72454) was tested in a greenhouse experiment using a completely randomized design. The experiment consisted of four replications of treatments in a factorial arrangement of 3 cultivars × 6 glyphosate dosages (0, 1,440, 2,160, 2,880, 3,600 and 4,320 g a. e. ha-1). Intoxication symptoms, based on a percentage scale ranging from 0 (no injury) to 100 % (total plant death), and total chlorophyll content were recorded at 1, 2, 3, 6, 7, 10, 20 and 34 days after glyphosate application (DAA). Shikimate dehydrogenase and α-esterase isoenzyme assays were performed at 8, 24, 48, 72 and 144 h after application (HAA). Intoxication symptoms observed at 6 DAA ranged from 5 % at the lowest glyphosate dosage (1,440 g a. e. ha-1) to ~30 % at the highest dosage (4,320 g a. e. ha-1) across all cultivars. IACSP94-4004 and IACSP93-3046 were determined to be the most glyphosate-tolerant cultivars. Reduction in chlorophyll content was observed with high dosages of glyphosate at 6 DAA. The shikimate dehydrogenase banding pattern was generally conserved among cultivars and treatments, with the exception of the IACSP94-4004 cultivar, which showed alterations in the banding pattern of α-esterase after glyphosate application. © 2013 Society for Sugar Research & Promotion.

Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Efeito da inoculação de fungos na atividade enzimática de solos e germinação de sementes de milho

Pós-graduação em Agronomia (Ciência do Solo) - FCAV

Comparação de atividades de enzimas liquóricas com achados histopatológicos do sistema nervoso central de cães com encefalite por cinomose

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determinação dos marcadores cardíacos e de lipoperoxidação em equinos sob influência de exercícios de alta e baixa intensidade em esteira de alta velocidade e suplementação com vitamina E (dl-alfa-tocoferol)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização isoenzimática e por anticorpos monoclonais dos agentes da leismaniose tegumentar americana (LTA) na mesorregião do Baixo Amazonas, estado do Pará, Brasil

Existe uma diversidade de espécies de Leishmania prevalentes na região Amazônica associadas à LTA configurando a etiologia múltipla da doença e, apesar do conhecimento da elevada ocorrência desta protozoose na Mesorregião do Baixo Amazonas, à oeste do Estado do Pará, quase nada era sabido sobre os agentes etiológicos da doença na referida área. Nesse sentido, o presente trabalho propôs-se a caracterizar por eletroforese de isoenzimas as amostras de Leishmania isoladas de pacientes procedentes da Mesorregião do baixo Amazonas, verificando a existência da correlação geográfica das espécies encontradas com a sua distribuição regional previamente conhecida, e ainda, verificando a presença de variação intraespecífica. A caracterização das 43 amostras de Leishmania foi feita por eletroforese em gel de amido utilizando sete sistemas enzimáticos (6PGDH, PGM, G6PD, MPI, GPI, ASAT E ALAT), comparando seus perfis eletroforéticos com os perfis das sete cepas-referência das espécies conhecidas da região. As amostras foram testadas previamente por imunofluorescência indireta com o uso de um painel com 23 anticorpos monoclonais (sistema biotina-avidina) apenas como uma triagem. A caracterização isoenzimática das amostras permitiu o seguinte resultado: 11 (25,28%) amostras de L. (V) braziliensis, 20 (46,50%) de L.(V) guyanensis, 2 (4,60%) de L.(L.) amazonensis, 4 (9,30%) de L.(V) shawi e 6 (13,95%) de L.(V) lainsoni. A eletroforese isoenzimática apresentou elevado poder discriminatório para a identificação das amostras estudadas, permitindo concluir que esta técnica representa uma importante ferramenta para a caracterização dos parasitos do gênero Leishmania. Nas cepas de L. (V) braziliensis observou-se pela primeira vez na Mesorregião do Baixo Amazonas a ocorrência de variação intraespecífica revelada pela presença de três serodemas. Nas cepas de L. (V) guyanensis observou-se a presença de duas variantes, uma que apresentou reatividade com o monoclonal B 19 (espécie-específico), porém com variação nas enzimas 6PGDH e PGM, e a Segunda, sem reatividade para este monoclonal e com perfis eletroforéticos semelhantes ao da cepa-referência L. (V) guyanensis especialmente nas enzimas 6PGDH, porém com tribandas, e na PGM, consideradas os melhores marcadores enzimáticos pelo seu elevado poder discriminatório. Dessa forma, descreveu-se pela primeira vez a ocorrência de diferentes espécies de Leishmania dermotrópicas na Mesorregião do Baixo Amazonas, as quais já tem registro na região norte do Brasil, sugerindo a transmissão simpátrica das espécies encontradas na referida área estudada.

Tirotoxicose experimental em gatos: efeitos sobre o tecido ósseo, isoenzimas da fosfatase alcalina e metaloproteínases de Matriz-2 E-9

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metabolismo oxidativo e cardíaco de equinos submetidos a exercício de baixa intensidade antes e após suplementação com antioxidante

The present study aimed to evaluate cardiac and lipoperoxidation markers in horses subjected to low intensity and long duration (TLD) exercise test, before and after vitamin E supplementation. For this purpose, 10 horses were used, subjecting them to the first TLD with a workload based on individual maximal oxygen uptake (VO2max). Then, horses received vitamin E (dl-alpha-tocopherol) during 59 days at a daily oral dose of 1,000IU, and thereafter they performed a second TLD with the same protocol as the first. Blood samples were collected to determine plasma malondialdehyde (MDA) as an index of lipoperoxidation, serum cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) as cardiac markers. As a result of the exercise, there was no significant increase in MDA or cTnI, but serum CK-MB increased suggesting myocardial stress. The supplementation was able to minimize reactive oxygen species production, as evidenced by lower concentrations of MDA at all times evaluated, but it didn't cause protective effect on the myocardium. It was concluded that the low intensity and long duration exercise promoted light myocardial stress in horses and vitamin E supplementation reduced lipoperoxidation.

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial Infarction

Background: The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.Objectives: To evaluate the predictors of systolic functional recovery after anterior AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).Methods: A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.Results: In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.Conclusion: In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction.

Efeito da suplementação com vitamina E sobre os metabolismos oxidativo e cardíaco em equinos submetidos a exercício de alta intensidade

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

First report of the characterization of the pathophysiological mechanisms caused by the freshwater catfish Pimelodus maculatus (order: Siluriformes)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Gastric and small intestinal lesions after partial stomach resection with Billroth II or Roux-en-Y reconstruction in the rat

The evolution and phenotypic expression of mucosal lesions of the gastric stump were investigated in male rats submitted to gastric resection with reconstruction by the Billroth II technique (BII with biliopancreatic reflux, BPR) or by the Roux-en-Y procedure (without BPR). Animals were studied at 24, 36, 54 and 64 weeks after surgery and the phenotypic expression of lesions analysed using routine hematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical concanavalin A, galactose oxidase Schiff (GOS) and sialidase GOS reactions). BPR was found to be responsible for the formation of adenomatous hyperplasia (AH), increasing in incidence and size with time, since the Roux-en-Y procedure failed to induce the gastric stump lesions observed after BII reconstruction. AHs always occurred in the transition of the gastrojejunal junction, a site offering special conditions for BPR influence, and were classified as gastric (G), intestinal (I) and G+I types according to their phenotypic expression. No pure I type AH was diagnosed at any time point. The G and G+I types developed at approximately equal incidences (i.e., G type 7/17, G+I type 10/17 at the 64th week). It was suggested that both gastric and intestinal mucosal elements were stimulated to proliferate by BPR, with the gastric mucosa tending to demonstrate AH. Intestinal type components of AH were found adjacent to the jejunum and not at the stomach margin, indicating an origin from intestinal mucosa. No metaplasia of the gastric mucosa was observed in any animal after partial gastric resection. In 101 rats submitted to the BII procedure, 5 mucinous adenocarcinomas were eventually diagnosed, mostly located in the subserosa of the gastrojejunal junction. All carcinomas expressed the phenotype of cells of the small intestine. Evidence of malignant transformation within the gastric components of AH was not observed even at the 64th week. In conclusion, all lesions induced by BPR in the rat remnant stomach are benign, and the few true cancers that arise in association are derived from the small intestine.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

Background: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Selektive und duale COX-1-, COX-2-Inhibitoren aus der Reihe der Methanone

Zusammenfassung: Prostaglandine (PG) sind wichtige biologische Entzündungsmediatoren, die aus der Arachidonsäure (AA) durch das Enzym Cyclooxygenase (COX) entstehen. Trotz einiger unerwünschter Wirkungen, sind Cyclooxygenase-Hemmer Mittel der Wahl zur Unterdrückung entzündlicher Prozesse. Von der Cyclooxygenase existieren zwei Isoenzyme: COX-1 und COX-2. Eine selektive Hemmung der COX-2 bzw. eine duale Hemmung der COX-1 und COX-2 wird als erfolgversprechendes Prinzip zur Behandlung von entzündlichen Erkrankungen diskutiert.Ziel der Arbeit war die Synthese und in vitro Testung sowie die Erstellung von Struktur-Wirkungs-Beziehungen selektiver bzw. dualer Hemmstoffe der COX-1/-2. Zusätzlich wurden die Substanzen auf inhibitorische Aktivität gegenüber der 5- und 12-Lipoxygenase untersucht.Ausgehend von der Struktur selektiver Hemmstoffe der COX-2 bzw. von dualen COX-1/ COX-2-Inhibitoren sowie von marktüblichen nichtsteroidalen Antirheumatika (NSAR), wurde das Diarylmethanon-Element als Basis gewählt. An diesem Strukturelement wurden Modifikationen vorgenommen, um selektive Hemmstoffe der COX-2 bzw. duale COX-1/ COX-2-Hemmstoffe zu erhalten.Die synthetisierten Verbindungen lassen sich in [4-(Methylsulfanyl)phenyl]- und [4-(Methylsulfonyl)phenyl](aryl)methanone, N-(Aroylphenyl)sulfonamide und -amide sowie (Hydroxyphenyl)(2-thienyl)methanone unterteilen.In der Reihe der [4-(Methylsulfanyl)phenyl](aryl)methanone sind potente Hemmstoffe sowohl der COX-1 als auch der COX-2 erhalten worden. Im Gegensatz dazu zeigen die [4-(Methylsulfonyl)phenyl](aryl)methanone gegenüber COX-1 und COX-2 keine inhibitorische Aktivität. Mit dem 2-Thienylderivat wurde ein potenter, dualer Hemmstoff beider Cyclooxygenase-Isoenzyme identifiziert, dessen Wirkstärke (bezüglich der COX-2) auf den Austausch von Phenyl gegen 2-Thienyl zurückzuführen ist.Die N-(Aroylphenyl)sulfonamide und -amide bilden die umfangreichste Gruppe bei den durchgeführten Untersuchungen, wobei besonders die regioisomeren N-(2-Aroylphenyl)sulfonamide und -amide eingehender studiert wurden. Auf der Basis der (2-Aroylphenyl)sulfonamide läßt sich für die Hemmung der COX-1 eine Struktur-Wirkungs-Beziehungen formulieren, die anhand Hilfe geeigneter Verbindungen überprüft wurde. Die Untersuchungen wurden zum Teil auch auf die 3- und 4-Regioisomeren ausgedehnt, wobei sich die erhaltenen Struktur-Wirkungs-Beziehungen bestätigten. Die Arylsulfonamide inhibieren bevorzugt die COX-1. Auch (4-Aroylphenyl)sulfonamide wurden auf mögliche inhibitorische Aktivität untersucht. Die Einbindung des Amidstickstoffs in ein Indolin- bzw. Tetrahydrochinolin-Ringsystem oder des Sulfonamids in ein 1,3-Propansultam führte in jedem Falle zu wenig aktiven Verbindungen gegenüber der COX-1. N-(2-Aroylphenyl)amide zeigten in Übereinstimmung mit der Hypothese an der COX-1 eine gute inhibitorische Aktivität.Aus der Reihe der (Hydroxyphenyl)(2-thienyl)methanone wurden die freien Alkohole, die Methylether und verschiedene Ester dargestellt und auf COX-1-Aktivität untersucht. Acetate, aber auch Phenole sind die potentesten Inhibitoren der COX-1. Als günstigte Positionen für die 2-Thienylcarbonyl-Einheit am Hydroxyphenylrest erweist sich die ortho- bzw. para-Position.

Funktionelle Bedeutung von P-Glykoprotein für Wirkungen und Nebenwirkungen von Antipsychotika

Therapeutisches Drug Monitoring (TDM) ist eine Maßnahme, bei der durch Messung der Medikamentenspiegel im Blut die Dosis ermittelt wird, bei der mit höchster Wahrscheinlichkeit mit Therapieansprechen gerechnet werden kann. Dabei wird angenommen, dass die Konzentrationen im Blut mit denen im Wirkkompartiment korrelieren. Für Antipsychotika wurde gezeigt, dass die Konzentrationen im Blut direkt mit denen im Gehirn korrelieren, die Verteilung zwischen den beiden Kompartimenten ist jedoch für die verschiedenen Antipsychotika sehr unterschiedlich. Die Distribution von Arzneistoffen zwischen Blut und Gehirn wird durch Effluxtransporter in der Blut-Hirn-Schranke kontrolliert. Welche Rolle dabei P-Glykoprotein (P-gp) für die Verteilung von atypischen Antipsychotika spielt und wie die Pharmakokinetik und –dynamik durch diesen Transporter beeinflusst werden, sollte in dieser Arbeit untersucht werden. Für die Messung des neu eingeführten Antipsychotikums Aripiprazol, sowie für seinen aktiven Metaboliten Dehydroaripiprazol, wurde eine hochleistungsflüssigchromatographische (HPLC) Methode mit Säulenschaltung und spektrophotometrischer Detektion etabliert. Die Methode wurde für die Messung von Serumproben schizophrener Patienten eingesetzt, um einen therapeutischen Bereich für Aripiprazol zu ermitteln. Aus der Analyse von 523 Patientenproben wurde herausgefunden, dass Aripiprazol-Serumkonzentrationen von 150 bis 300 ng/ml mit gutem klinischen Ansprechen und einem geringen Risiko für Nebenwirkungen einhergingen. Weiterhin wurde festgestellt, dass die Serumspiegel bei gleichzeitiger Gabe von Inhibitoren und Induktoren der Cytochrom P450 (CYP) Isoenzyme CYP2D6 und CYP3A4 erhöht bzw. gesenkt wurden. Am Modell der P-gp Knockout Maus im Vergleich zu FVB Wildtyp Mäusen wurden Konzentrationsverläufe von Antipsychotika nach i.p. Gabe von Amisulprid, Aripiprazol, Dehydroaripiprazol, Clozapin, Desmethylclozapin, Haloperidol, Olanzapin, Quetiapin, Risperidon und 9-Hydroxyrisperidon sowie der Kontrollsubstanz Domperidon im Gehirn und Blut über 24 Stunden mittels HPLC-Methoden gemessen. Welchen Einfluss eine verminderte Expression von P-gp auf die Pharmakodynamik hat, wurde in zwei Verhaltenstests untersucht. Mit Hilfe des Rotarods wurden motorische Effekte der Arzneistoffe erfasst und mittels Radial Arm Water Maze kognitive Fähigkeiten. Risperidon und sein aktiver Metabolit 9-Hydroxyrisperidon waren die stärksten Substrate von P-gp. 10-fach höhere Konzentrationen im Gehirn der P-gp Knockout Mäuse führten zu 10-fach stärkeren Beeinträchtigungen in den pharmakodynamischen Untersuchungen im Vergleich zu Wildtyp Tieren. Amisulprid, Aripiprazol, Dehydroaripiprazol, Desmethylclozapin und Quetiapin konnten ebenfalls als Substrate von P-gp identifiziert werden. Olanzapin, Haloperidol und Clozapin wurden durch P-gp wenig bzw. nicht in ihrer Pharmakokinetik und –dynamik beeinflusst. Da P-gp von Nagern und Menschen nach derzeitiger Kenntnis in ihren Substrateigenschaften weitgehend übereinstimmen, muss bei einer Behandlung von schizophrenen Patienten mit Antipsychotika, die als Substrate von P-gp identifiziert wurden, davon ausgegangen werden, dass eine Veränderung der Expression oder Aktivität von P-gp, genetisch verursacht oder durch Medikamente bedingt, für das Therapieansprechen oder das Auftreten von Nebenwirkungen bedeutsam sind.