Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados

FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA) pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g) foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min) e reperfundidos (30 min) com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max) e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73%) e à isquemia de 30 min (~ 80%) vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE) e a pressão de perfusão (PP) foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente) e à isquemia de 30 min (6 e 1,10 vezes, respectivamente) vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94%) em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente) apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.

Micronutrientes antioxidantes e risco cardiovascular em pacientes com diabetes: uma revisão sistemática

FUNDAMENTO: Associações inversas entre a ingestão de micronutrientes e desfechos cardiovasculares foram demonstradas previamente na população geral. OBJETIVO: Revisar sistematicamente o papel de micronutrientes no desenvolvimento/presença de desfechos cardiovasculares em pacientes com diabetes. MÉTODOS: Foi realizada uma busca nas bases de dados Medline, Embase e Scopus (Janeiro/1949-Março/2012) por estudos observacionais que avaliaram micronutrientes antioxidantes e desfechos cardiovasculares em pacientes com diabetes e, em seguida, os dados foram selecionados e extraídos (dois revisores independentes). RESULTADOS: Dos 15658 estudos identificados, cinco foram incluídos, sendo três de caso-controle e dois de coorte, com um acompanhamento de 7-15 anos. Uma metanálise não foi realizada devido aos diferentes micronutrientes antioxidantes (tipos e métodos de medição) e os desfechos avaliados. Os micronutrientes avaliados foram: vitamina C (dieta e/ou suplementação), cromo e selênio em amostras de unha, e α-tocoferol e zinco no soro. A ingestão de > 300 mg de vitamina C a partir de uplementos esteve associada a um risco aumentado de doença cardiovascular, doença arterial coronariana (DAC) e acidente vascular cerebral (RR 1,69-2,37). Altos níveis de α-tocoferol no soro foram associados a um risco 30% inferior de DAC em outro estudo (RR 0,71, IC 95% 0,53-0,94). Entre os minerais (zinco, selênio e cromo), foi observada uma associação inversa entre o zinco e a DAC: níveis inferiores a 14,1 μmol/L foram associados a um risco aumentado para DAC (RR 1,70, IC 95% 1,21-2,38). CONCLUSÃO: A informação disponível sobre essa questão é escassa. Estudos prospectivos adicionais são necessários para elucidar o papel desses nutrientes no risco cardiovascular de pacientes com diabetes.

Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

Background: Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Background:Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).Objective:To investigate the relationships between p.Q192R SNP ofPON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317).Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques.Conclusion:In low-risk individuals, the presence of the p.192Q variant ofPON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

Abstract Background: Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective: The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods: Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results: Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

Psychosoziale Unterstützung von Kindern und Jugendlichen mit Juveniler Neuronaler Ceroid-Lipofuszinose

In dieser Bachelorarbeit soll die psychosoziale Situation von Kindern und Jugendlichenmit juveniler Neuronaler Ceroid-Lipofuszinose (JNCL) untersucht werden. Sie ist eine derhäufigsten, erblichen neurodegenerativen Stoffwechselerkrankungen bei Kindern undJugendlichen. Die Hauptsymptomatiken sind Blindheit, Epilepsie und Demenz. Diese Erkrankungist nicht heilbar und führt zu einem frühen Tod der Betroffenen. Oftmals erfolgtdie erste Diagnose beim Augenarzt, da zuerst die Erblindung eintritt. Beim Kinderneurologenerfolgt schließlich die endgültige Diagnose JNCL. Nun gilt es, das betroffene Kind undseine Angehörigen so gut wie möglich zu unterstützen. Dies geschieht auf medizinischer,schulischer/pädagogischer, psychologischer, sowie psychosozialer Basis. Bezüglich dermedizinischen Unterstützung sind sowohl die Spezialsprechstunde für neurodegenerativeErkrankungen im Universitätsklinikum Hamburg-Eppendorf (UKE), sowie Maßnahmen wiePhysio-, Ergo oder Logopädie hilfreich. In manchen Fällen sind auch die Maßnahmen dersozialmedizinischen Versorgung notwendig. In der Schule ist eine an das betroffene Kindangepasste Form der Beschulung wichtig. Zur psychologischen Begleitung und Konfliktlösungkann die supportive Psychotherapie genutzt werden. Selbsthilfegruppen und dieBeratung durch Sozialpädagogen in der Schule oder Behindertenwerkstatt übernehmendie psychosoziale Versorgung der betroffenen Kinder und Angehörigen. An zwei Fallbeispielensoll die praktische Umsetzung der Unterstützungsmöglichkeiten gezeigt werden.

Ocorrência do órgão cupuliforme com bordos pelífenos, no colo dos "seedlings" de algumas Myrtaceae

After verifing the presence of the cupuliform organ on the seedlings from 105 species of Eucalyptus (ACCORSI, 1955-56), the author concluded that it is a morphological characteristic of the genus, which is peculiar to the plants only in first stages of their life. In this paper, the author resumes his study carried out on 20 species of Myrtaceae, distributed among 13 genus and he could certify, until now, that, in relation to the cupuliform organ, they may divided in three groups: 1.° Group - Without cupuliform organ 1. Campomanesia aurea Berg 2. Eugenia campestris DC. 3. Eugenia tomentosa Camb. 4. Eugenia uniflora L. 5. Myrciaria edulis Berg 6. Myrciaria trunciflora Berg 7. Pitangueira-gigante - As it was difficulty to identify this species, I use its common name. 2.° Group - With rudiment of cupuli orm organ 1. Eugenia uvalha Camb. 2. Jambosa vulgaris DC. 3. Myrciaria cauliflora Berg 3.° Group - With full cupuliform organ 1. Amomyrtus luma (Mol) Legr. et Kaus. 2. Blepharocalyx angustifolius Berg 3. Britoa acida Berg 4. Callistemon speciosus DC. o. Callistemon viminalis Cheel. 6. Feijoa sellowiana Berg 7. Myrceugenia glaucescens (Camb.) Legrand 8. Myrrhinium rubriflorum Berg 9. Psidium guayava Raddi 10. Psidium littorale Raddi During his observations, he could identify also in many, seeds an "operculum", further observations about it will be published opportunely.

Familiengründung- Chancen und Risiken der Transition anhand von zwei Fallbeispielen

[s.c.]

Indução do crescimento ovariano em Aegla uruguayana (Crustacea, Anomura, Aeglidae) mediante a incorporação de neuroreguladores ao alimento

O efeito estimulante da spiperona e da naloxana sob a maturação ovariana foram avaliados em fêmeas de Aegla uruguayana Schmitt, 1942 e, para isto, tais neuroreguladores foram incorporados ao alimento e administrados a uma dose de 10-8 mol/animal a cada sessão de alimentação. Fêmeas adultas foram coletadas com puçá em um arroio próximo à cidade de Salto, Província de Buenos Aires, Argentina. Dez fêmeas foram sacrificadas, medidas, pesadas e os seus ovários foram retirados e pesados para a determinação do índice gonadossomático (IG). As demais fêmeas (30) foram divididas em três grupos experimentais - (a) controle: alimentadas com pellets controle composto por ração para peixe - 34% de proteína e 43% de proteína; (b) spiperona: alimentadas com pellets controle enriquecidos com spiperona; (c) naloxana: alimentadas com pellets controle enriquecidos com naloxana. Após 7 semanas as fêmeas foram sacrificadas e avaliado o IG. Os ovários e o hepatopâncreas foram quantificados quanto aos níveis de lipídeos totais e colesterol. A naloxana produziu um aumento significativo nos níveis de lipídeos tanto nas gônadas como no hepatopâncreas em relação ao grupo controle. A spiperona produziu aumento significativo nos níveis de lipídeos nas gônadas e no hepatopâncreas e de colesterol no hepatopâncreas quando comparados ao controle. Os níveis de lipídeos foram significativamente menores na hemolinfa das fêmeas que foram alimentadas com pellets com spiperona e maiores nas fêmeas tratadas com naloxana quando comparadas as fêmeas que foram alimentadas apenas com ração. A spiperona e a naloxana, ao inibir os efeitos da dopamina e dos opióides endógenos, provavelmente causaram a secreção do hormônio estimulante das gônadas e a inibição do hormônio inibidor das gônadas, causando, portanto indução do desenvolvimento ovariano. Tal hipótese é reforçada pelos aumentos do índice gonadossomático verificado nestes grupos experimentais.

De la caça-recol·lecció a l’agricultura i ramaderia: una aproximació a la dieta i l’explotació dels recursos forestals a partir del registre arqueobotànic

Estudi elaborat a partir d’una estada a l’Institut of Archaeology de la University College of London i a jaciments arqueològics espanyols. L’objectiu ha estat l’aprenentatge del mètode carpològic a través de l’anàlisi de fruit i llavors recuperades a jaciments de cronologies paleolítiques i l’estudi de les col·leccions de referència de Institute of Archaeology. Els jaciments analitzats han estat el Molí del Salt (Vimbodí, Tarragona) i Atapuerca (Burgos). L’estudi de mostres carpològiques de jaciments Neolítics d’una regió del Nord de Xina han permès l’apropament previ a restes de cronologies més recents dels primers agricultors i ramaders.

Carcinoembryonic antigen (CEA) in non digestive cancerous and normal tissues.

Carcinoembryonic antigen (CEA), immunologically identical to CEA derived from colonic carcinoma, was identified and purified from perchloric acid (PCA) extracts of bronchial and mammary carcinoma. CEA extracted from bronchial and mammary carcinoma was quantitated by single radial immunodiffusion and was found to be in average about 50-75 times less abundant in these tumors than in colonic carcinoma. CEA could also be detected in one normal breast in lactation and at lower concentrations in normal lung (1000-4000 times lower than in colonic carcinoma). The small amounts of CEA present in normal tissues are distinct from the glycoprotein of small mol. wt showing only partial identity with CEA, that we recently identified and extracted in much larger quantities from normal lung and spleen. The demonstration of the presence of CEA in non digestive carcinoma by classical gel precipitation analysis suggests that the CEA detected in the plasma of such patients by radioimmunoassay is also identical to colonic carcinoma CEA. Our comparative study of plasma CEA from bronchial and colonic carcinoma, showing that CEA from both types of patient has the same elution pattern on Sephadex G-200 and gives parallel inhibition curves in the radioimmunoassay, is in favor of this hypothesis. However, it should not be concluded that all positive CEA radioimmunoassay indicate the presence of an antigen identical to colonic carcinoma CEA. A word of warning concerning the interpretation of radioimmunoassay is required by the observation that the addition of mg amounts of PCA extract of normal plasma, cleared of CEA by Sephadex filtration, could interfere in the test and mimic the presence of CEA.

Metabolic and respiratory effects of infused sodium acetate in healthy human subjects.

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.

Switch to Sirolimus-based immunosuppresion in stable renal transplant recipients

Purpose: Sirolimus (SRL) has been used to replace calcineurin inhibitors (CNI) for various indications including CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of switching from CNI to SRL in stable renal transplant recipients (RTR) with low grade proteinuria (<1 g/24 h). Methods and materials: Between 2001 and 2007, 41 patients (20 females, 21 males; mean age 47 ± 13) were switched after a median time post-transplantation of 73.5 months (range 0.2-273.2 months). Indications for switch were CNI nephrotoxicity (39%), thrombotic micro-angiopathy (14.6%), post-transplantation cancer (24.4%), CNI neurotoxicity (7.4%), or others (14.6%). Mean follow-up after SRL switch was 23.8±16.3 months. Mean SRL dosage and through levels were 2.4 ± 1.1 mg/day and 8 ± 2.2 ug/l respectively. Immunosuppressive regiments were SRL + mycophenolate mofetil (MMF) (31.7%), SRL + MMF + prednisone (36.58%), SRL + prednisone (19.51%), SRL + Azathioprine (9.75%), or SRL alone (2.43%). Results: Mean creatinine decreased from 164 to 143 μmol/l (p <0.03), mean estimated glomerular filtration rate (eGFR) increased significantly from 50.13 to 55.01 ml/minute (p <0.00001), mean systolic and diastolic blood pressure decreased from 138 to 132 mm Hg (p <0.03) and from 83 to78 mm Hg (p <0.01), but mean proteinuria increased from 0.21 to 0.63 g/24 h (p <0.001). While mean total cholesterolemia didn't increased significantly from 5.09 to 5.56 mmol/l (p = 0.06). The main complications after SRL switch were dermatitis (19.5%), urinary tract infections (24.4%), ankle edema (13.3%), and transient oral ulcers (20%). Acute rejection after the switch occurred in 7.3% of patients (n = 3), and 2 acute rejections were successfully treated with corticosteroids and 1 did not respond to treatment (not related to switch). SRL had to be discontinued in 17% of patients (2 nephrotic syndromes, 2 severe edema, 1 acute rejection, 1 thrombotic micro-angiopathy, and 1 fever). Conclusion: In conclusion, we found that switching from CNI to SRL in stable RTR was safe and associated with a significant improvement of renal function and blood pressure. Known side-effects of SRL led to drug discontinuation in less than 20% of patients and the acute rejection rate was 7.3%. This experience underlines the importance of patient selection before switching to SRL, in particular regarding preswitch proteinuria.

Analysis of toxoplasma gondii proteins after Triton X-114 solubilization and hidropholic chromotograhy

The distribution of the surface proteins of toxoplasma gondii radiodinated were studied using the phase separation technique and ability of binding in the phenyl-Sepharose column. Eight polypeptides with Mr 22 to 180 distributed exclusively in the detergent rich-phase, while six polypeptides with mol. wt. 15,000 to 76,000 distributed exclusively in the detergent poor-phase. Twopolypeptides with 15,000 and 70,000 distributed on both phase. All the polypeptides present in the detergent rich-phase binding in the phenyl-Sepharose column, and can be isolated in two peak according with their relative hydrophobicities.two polypeptides hydrophobic with Mr 60 and 66 recognized by human serum were isolated by the association of the two technique. Our result showed that the surface proteins of t. gondii present different degrees of hydrophobicity and that the use of hydrophobic interaction chromatography after Triton X-114 extraction may be an important isolation method of membrane proteins.

Compartmentalized Cerebral Metabolism of [1,6-(13)C]Glucose Determined by in vivo (13)C NMR Spectroscopy at 14.1 T.

Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining (13)C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V(TCA)) and neurotransmission rate (V(NT)) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V(TCA) was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V(PC)) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.