A Case of Chronic Mesenteric Ischemia imitating Crohn's disease

Objectives: We present an atypical case of chronic mesenteric ischemia with weight loss as only clinical manifestation and endoscopic findings imitating Crohn´s disease. Materials and Methods: A CT Angiography of abdomen confirmed the diagnosis of mesenteric ischemia after total occlusion of celiac trunk and superior mesenteric artery. Results: The patient died due to severe sepsis, as a result of extended bowel infarction. Conclusions: The diagnosis of chronic mesenteric ischemia requires a high degree of clinical suspicion and can be life-saving if early conducted.

Efeitos cardiovasculares da transferência adotiva de linfócitos T reguladores em camundongos submetidos à infusão crônica de angiotensina II e de aldosterona

A angiotensina (Ang) II e aldosterona induzem hipertensão arterial por mecanismos em parte mediados pela imunidade adaptativa, envolvendo linfócitos T auxiliares respondedores (Tresp). Os linfócitos T reguladores (Treg) são capazes de suprimir os efeitos próinflamatórios do sistema imune. O presente estudo avaliou se a transferência adotiva de Treg é capaz de prevenir a hipertensão e a lesão vascular induzidas pela Ang II ou pela aldosterona, em dois protocolos distintos. No protocolo com Ang II, camundongos machos C57BL/6 sofreram a injeção endovenosa de Treg ou Tresp, sendo depois infundidos com Ang II (1μg/kg/min), ou salina (grupo controle) por 14 dias. No protocolo com aldosterona, um outro conjunto de animais sofreu injeções de Treg ou Tresp, sendo depois infundido com aldosterona (600μg/kg/d) ou salina (grupo controle), pelo mesmo intervalo de tempo. O grupo tratado com aldosterona recebeu salina 1% na água. Tanto o grupo Ang II como aldosterona apresentaram elevação da pressão arterial sistólica (43% e 31% respectivamente), da atividade da NADPH oxidase na aorta (1,5 e 1,9 vezes, respectivamente) e no coração (1,8 e 2,4 vezes, respectivamente) e uma redução da resposta vasodilatadora à acetilcolina (de 70% e 56%, respectivamente), quando comparados com os respectivos controles (P<0,05). Adicionalmente, a administração de Ang II proporcionou um aumento rigidez vascular (P<0,001), na expressão de VCAM-1 nas artérias mesentéricas (P<0,05), na infiltração aórtica de macrófagos e linfócitos T (P<0,001) e nos níveis plasmáticos das citocinas inflamatórias interferon (INF)-γ, interleucina (IL)-6, Tumor necrosis factor (TNF)-α e IL-10 (P<0,05). Ang II causou uma queda de 43% no número de células Foxp3+ no córtex renal, enquanto que a transferência adotiva de Treg aumentou as células Foxp3+ em duas vezes em comparação com o controle. A administração de Treg preveniu o remodelamento vascular induzido pela aldosterona, observado na relação média/lúmen e na área transversal da média das artérias mesentéricas (P<0,05). Todos os parâmetros acima foram prevenidos com a administração de Treg, mas não de Tresp. Estes resultados demonstram que Treg são capazes de impedir a lesão vascular e a hipertensão mediadas por Ang II ou por aldosterona, em parte através de ações antiinflamatórias. Em conclusão, uma abordagem imuno-modulatória pode prevenir o aumento da pressão arterial, o estresse oxidativo vascular, a inflamação e a disfunção endotelial induzidos por Ang II ou aldosterona.

Efeito do extrato de Euterpe oleracea Mart.(Açaí) sobre a disfunção endotelial, estresse oxidativo e alterações vasculares e renais associados à hipertensão renovascular dois rins, 1 clip (2R,1C)

Estudos recentes mostram que o açaí é rico em polifenóis e uma dieta rica em polifenóis pode estar envolvida na proteção contra o risco cardiovascular. O objetivo deste estudo foi avaliar o efeito do tratamento crônico de animais hipertensos 2R,1C com extrato hidroalcoólico do caroço do açaí (ASE) sobre o desenvolvimento da hipertensão e disfunção endotelial; estresse oxidativo e sobre as alterações vasculares e renais. Ratos Wistar machos foram utilizados para obtenção da hipertensão renovascular 2R,1C e ratos controles 2R (sham) foram somente submetidos à laparotomia e receberam tratamento diário com veículo ou ASE (200 mg/Kg/dia) durante 40 dias. A pressão arterial sistólica (PAS) foi aferida por pletismografia de cauda e os efeitos vasodilatadores da acetilcolina (ACh) e nitroglicerina (NG) foram estudados em leito arterial mesentérico (LAM) perfundido e pré-contraído com norepinefrina. A atividade das enzimas SOD, CAT, GPx, os níveis de MDA, a carbonilação de proteínas e os níveis de nitrito foram avaliados por espectrofotometria. As expressões de enzimas pró e antioxidantes foram avaliadas por western blot. A atividade de MMP-2 foi avaliada por zimografia. Os níveis séricos de creatinina foram avaliados através de kit, por espectrofotometria. As alterações vasculares e renais foram avaliadas por microscopia de luz. A PAS foi maior nos animais 2R,1C, e o tratamento com ASE preveniu o desenvolvimento da hipertensão. O efeito vasodilatador reduzido da ACh em animais 2R,1C foi recuperado pelo ASE. O efeito vasodilatador da NG não foi diferente entre os grupos. O dano oxidativo avaliado pela peroxidação lipídica e carbonilação de proteínas foi maior nos animais 2R,1C, e reduzido pelo tratamento com ASE. As atividades da SOD, CAT e GPx foram menores em amostras de mesentério, plasma, rim e coração de animais 2R,1C e o tratamento com ASE aumentou estas atividades. A produção de NO foi menor no plasma, mesentério e rim dos animais 2R,1C, e o tratamento com ASE aumentou a produção de NO somente no rim e mesentério destes animais. A expressão de SOD-1, 2, eNOS e TIMP-1 foram menores nos animais 2R,1C e o tratamento com ASE aumentou a expressão destas enzimas. A expressão de NOX-4 e MMP-2 e a atividade de MMP-2 foram maiores nos animais 2R,1C e o tratamento com ASE reduziu a expressão destas enzimas e a atividade de MMP-2. Os animais 2R,1C apresentaram um aumento na espessura da camada média da aorta e artéria mesentérica e um aumento na relação média/lúmen da aorta, e estas alterações foram prevenidas pelo ASE. Os níveis séricos aumentados de creatinina nos animais 2R,1C foram reduzidos por ASE. As alterações morfológicas renais nos animais 2R,1C foram prevenidas pelo ASE. Portanto, o tratamento com ASE previne o desenvolvimento da hipertensão, melhora a disfunção endotelial e previne as alterações vasculares e renais em ratos 2R,1C. A redução da atividade antioxidante e o aumento na peroxidação lipídica e carbonilação de proteínas sugerem o envolvimento de um mecanismo deficiente da defesa antioxidante e de um dano oxidativo aumentado, os quais foram revertidos pelo ASE.

Effect of purinergic blockers on outward current in isolated smooth muscle cells of the sheep bladder

Freshly dispersed cells from sheep urinary bladder were voltage clamped using the whole cell and inside-out patch-clamp technique. Cibacron and Basilen blue increased outward current in a dose-dependent manner with a half-maximal response at 10(-5) M. Suramin, in concentrations to 10(-3) M, had no such effect. The Cibacron blue response was abolished in Ca2+-free physiological salt solution, suggesting that it was acting on a Ca2+-dependent current. Similarly, the Cibacron blue-sensitive current was significantly attenuated by charybdotoxin. Cibacron blue did not modulate inward current nor were its effects modified by caffeine or heparin, suggesting that its effect on outward current was not secondary to an increase in intracellular Ca2+. Application of 10(-4) M Cibacron blue to the inside membrane of excised patches caused a rapid increase in open probability of a large-conductance (300 pS) K+ channel. These results suggest that Cibacron blue is a potent activator of a Ca2+-dependent outward current in bladder smooth muscle cells in addition to its action as a purinergic blocker.

The Gastrointestinal Peptide Obestatin Induces Vascular Relaxation Via Specific Activation of Endothelium-Dependent Nitric Oxide Signalling.

Background and purpose: Obestatin is a recently-discovered gastrointestinal peptide with established metabolic actions, which is linked to diabetes and may exert cardiovascular benefits. Here we aimed to investigate the specific effects of obestatin on vascular relaxation. Experimental approach: Cumulative relaxation responses to obestatin peptides were assessed in isolated rat aorta and mesenteric artery (n=8) in the presence/absence of selective inhibitors. Complementary studies were performed in cultured bovine aortic endothelial cells (BAEC). Key results: Obestatin peptides elicited concentration-dependent relaxation in both aorta and mesenteric artery. Responses to full-length obestatin(1-23) were greater than those to obestatin(1-10) and obestatin(11-23). Obestatin(1-23)-induced relaxation was attenuated by endothelial denudation, L-NAME (NO synthase inhibitor), high extracellular K(+) , GDP-ß-S (G protein inhibitor), MDL-12,330A (adenylate cyclase inhibitor), wortmannin (PI3K inhibitor), KN-93 (CaMKII inhibitor), ODQ (guanylate cyclase inhibitor) and iberiotoxin (BK(Ca) blocker), suggesting that it is mediated by an endothelium-dependent NO signalling cascade involving an adenylate cyclase-linked G protein-coupled receptor, PI3K/Akt, Ca(2+) -dependent eNOS activation, soluble guanylate cyclase and modulation of vascular smooth muscle K(+) . Supporting data from BAEC indicated that nitrite production, intracellular Ca(2+) and Akt phosphorylation were increased after exposure to obestatin(1-23). Relaxations to obestatin(1-23) were unaltered by inhibitors of candidate endothelium-derived hyperpolarising factors (EDHFs) and combined SK(Ca) /IK(Ca) blockade, suggesting that EDHF-mediated pathways were not involved. Conclusions and Implications: Obestatin produces significant vascular relaxation via specific activation of endothelium-dependent NO signalling. These actions may be important in normal regulation of vascular function and are clearly relevant to diabetes, a condition characterised by endothelial dysfunction and cardiovascular complications.

Embolização das artérias prostáticas no tratamento da hiperplasia benigna da próstata : estudo anátomo-clínico

Resumo: A hiperplasia benigna da próstata (HBP) tem elevada prevalência nos homens entre os 50 e 79 anos de idade, sendo ubiquitária com o envelhecimento. Devido à significativa morbi-mortalidade associada aos tratamentos médicos e cirúrgicos currentemente disponíveis, são necessárias novas tecnologias para melhorar os resultados e minimizar o desconforto dos doentes. Recentemente, estudos preliminares de experimentação animal e em 3 doentes tratados, sugeriram a embolização arterial prostática selectiva (EAPS) como hipótese terapêutica para a HBP. Decidimos investigar se a EAPS poderia ser um procedimento bem sucedido no tratamento da HBP gravemente sintomática. Para tal realizámos um estudo anátomo-radiológico e clínico em 63 doentes com recurso a uma terapêutica inovadora minimamente invasiva guiada pela imagem. Avaliámos 126 hemipélvis com recurso a Angio-RM, Angio-TC e Angiografia Digital de Subtracção, com o intuito de definir os padrões básicos de bifurcação das artérias ilíacas internas até agora apenas descritos em estudos cadavéricos. Estudámos ainda o suprimento vascular arterial prostático, identificando: 1 as artérias prostáticas; 2 origem e direcção; 3 os ramos intra-prostáticos; 4 anastomoses com outras artérias. Em relação aos resultados anatómicos, identificámos 181 artérias prostáticas, já que em 43.7% das hemipélvis existiam dois pedículos arteriais prostáticos com origens independentes. A origem mais frequente foi a artéria pudenda interna (39.7%), seguida do tronco comum glúteo-pudendo (21%) e da artéria vesical superior (18.2%). Origens menos frequentes foram a artéria obturadora (12.1%), as artérias glúteas inferior (3.9%)ou superior (1.7%), ramos rectais provenientes da artéria mesentérica inferior (1.7%) e a artéria pudenda acessória (1.7%). Identificaram-se anastomoses com as artérias adjacentes em 57.9% dos casos: com a terminação da artéria pudenda interna (41.6%),artérias prostáticas contra-laterais (18.2%) e homo-laterais (11.7%), com ramos rectais (15.6%) e com artérias vesicais (12.9%). Em relação ao estudo clínico tratámos 63 doentes (idades compreendidas entre 52 - 82 anos, média 69.5 anos) com HBP gravemente sintomática refractária à terapêutica médica há mais de 6 meses. Foi possível avaliação após o tratamento em 37 doentes: média de seguimento de 4.7 meses (variando entre 1 e 12 meses). A EAPS unilateral foi possível em todos os doentes, com embolização bilateral em 73% dos casos. A embolização bilateral não foi possível em 27% dos casos devido a tortuosidade, alterações ateroescleróticas e pequeno calibre das artérias ilíacas e/ou prostáticas. Em média houve uma melhoria do International Prostate Symptom Score (IPSS) de 10.8 pontos, da QoL de 1.5 pontos e do Internationl Index of Erectile Function (IIEF) de 2.1 pontos. Houve uma redução média do PSA de 30% (2.4 ng/mL), um aumento do pico de fluxo urinário (Qmax) de 3.1 - 3.85 mL/s e uma redução média do volume prostático de 21% (18.5 mL). Registou-se uma complicação major: pequena área de isquémia da parede vesical tratada cirurgicamente. Em 75% dos doentes tratados obteve-se sucesso clínico com franca melhoria dos sintomas, enquanto 25% dos doentes foram considerados insucesso clínico por se ter registado uma fraca ou ausente melhoria sintomática após a embolização. Os restantes doentes tratados estão sob controlo evolutivo, pararam toda a medicação prostática, sem qualquer caso de disfunção sexual associada com o tratamento. Este trabalho constitui o primeiro estudo anatómico descritivo in vivo das artérias prostáticas, conseguido devido à utilização de técnicas de imagem nunca usadas para este fim. O uso clínico dos dados anatómicos acima referidos permitiu a implementação de técnicas de Radiologia de Intervenção no tratatamento de uma doença de elevada prevalência. ------------------------------- ABSTRACT: Benign prostatic hyperplasia (BPH) has high prevalence in men aged 50–79 years being ubiquitous with aging. Due to significant morbi-mortality associated with currently available medical and surgical treatments, there is the need for innovative technologies to continue to improve outcomes and minimize patient discomfort and morbidity. Recently, prostatic arterial embolization (PAE) was suggested as a treatmentoption for BPH based on preliminary results from animal studies and 3 treated patients. We decided to investigate if PAE might be a successful treatment option for severely symptomatic BPH patients. We performed a clinical and anatomical-radiological study in 63 patients with the use of an inovative image-guided minimally invasive technique. We evaluated 126 pelvic sides using Angio-MR or Angio-CT and Catheter Angiography before embolisation to treat symptomatic BPH. We aimed to define the main branching patterns of the male internal iliac arteries, so far only studied in the cadaver. We also evaluated the prostatic arterial supply, identifying: 1 the prostatic arteries; 2 origin and direction; 3 intra-prostatic branches; 4 anastomoses with surrounding arteries. Regarding the anatomical study we identified 181 prostatic arteries, because in 43.7% of pelvic sides 2 separate prostatic vascular pedicles were found. The most frequent origin was the internal pudendal artery (39.7%) with the common glutealpudendal trunk (21%) and superior vesical arteries (18.2%) the next commonest. Less frequent origins were the obturator artery (12.1%), the inferior (3.9%) or superior (1.7%) gluteal arteries, rectal branches from the inferior mesenteric artery (1.7%) and the accessory pudendal artery (1.7%). There were anastomoses with the surrounding arteries in 57.9% of cases: termination of the internal pudendal artery (41.6%), contralateral prostatic arteries (18.2%), same-side prostatic arteries (11.7%), rectal branches (15.6%), and vesical arteries (12.9%).Regarding the clinical study, we treated 63 patients aged 52–82 years (mean 69.5 years) who presented with symptomatic BPH refractory to medical treatment for at least 6 months. Follow-up evaluation (mean 4.7 months, range 1-12 months) was possible in 37 patients. PAE was achieved in all patients with bilateral embolization in 73%. In 27% PAE was performed unilaterally due to tortuosity, atherosclerotic changes and small size of iliac and prostatic arteries. There was a mean decrease in the IPSS of 10.8 points, a mean improvement in QoL of 1.5 points, and a mean increase in the sexual function score of 2.1 points. There was a mean PSA reduction of 30% (2.4 ng/mL), a Qmax increase of 3.1 to 3.85 mL/sec, and a mean prostate volume decrease of 21% (18.5 mL). There was one major complication: a small area of bladder wall ischemia treated by surgery. Overall, 75% of patients were considered clinical success with major improvement after PAE, while 25% of patients were considered clinical failure with little or no improvement after PAE. All remaining patients are under follow-up, stopped all prostatic medication, and reported no sexual dysfunction. This study is the first one to describe the radiological anatomy of the prostatic arteries, with the use of imaging techniques never used for this purpose before. The clinical use of the anatomical findings allowed the implementation of Interventional Radiology tehniques in the treatment of a disease with a high prevalence.

Prostaglandine E2 et mesures du flux mésentérique par Doppler à la suite d’un traitement du canal artériel à l’ibuprofène par voie intraveineuse et entérale chez les bébés prématurés

En dépit du nombre croissant d’études cliniques sur le canal artériel (CA), des failles méthodologiques entretiennent plusieurs incertitudes concernant l’efficacité et la sécurité des traitements chez les bébés nés prématurés. L’objectif de cette recherche était de comparer les concentrations de prostaglandine E2 (PGE2) et les mesures du flux mésentérique par échographie Doppler chez les enfants nés prématurément et ayant un canal artériel traité à l’ibuprofène par voie intraveineuse ou entérale, en utilisant la méthodologie randomisée contrôlée et à double insu. Dans notre étude pilote, 20 nouveau-nés prématurés de moins de 34 semaines ayant un CA symptomatique confirmé par échocardiographie, furent randomisés au traitement à l’ibuprofène par voie intraveineuse ou entérale. La voie d’administration fut maintenue à l’insu de l’équipe traitante, des cardiologues et des investigateurs. Des dosages des prostaglandines plasmatiques ont été mesurés avant le début du traitement ainsi que 3, 24 et 48 h après le début du traitement. Les mesures du flux mésentérique ont été effectuées avant le traitement à l’ibuprofène ainsi que 1 h et 3 h après le traitement. Nous avons démontré à partir de nos observations que les niveaux plasmatiques de prostaglandines E2 diminuent chez les patients ayant répondu au traitement à l’ibuprofène, indépendamment de la voie d’administration. Nous n’avons pas observé de changement dans l’évolution des dosages de PGE2 chez les patients qui n’ont pas répondu au traitement. Les paramètres mesurés par échographie Doppler au niveau de l’artère mésentérique supérieure n’étaient pas affectés par la voie d’administration du traitement à l’ibuprofène, intraveineuse ou entérale. La présente étude suggère ainsi que le traitement du CA par ibuprofène intraveineux ou entéral n’influe pas sur le flux sanguin mesuré par échographie Doppler. La baisse de la prostaglandine E2 coïncide avec la fermeture du CA, et son dosage pourrait jouer un rôle dans la gestion du traitement. Nous avons démontré la faisabilité d’une étude clinique randomisée à double insu dans le traitement du canal artériel; une méthodologie qui devrait désormait être employé dans la recherche clinique sur les traitements de la persistance du CA.

The reactions of specific neuron types to intestinal ischemia in the guinea pig enteric nervous system

Damage following ischemia and reperfusion (I/R) is common in the intestine and can be caused during abdominal surgery, in several disease states and following intestinal transplantation. Most studies have concentrated on damage to the mucosa, although published evidence also points to effects on neurons. Moreover, alterations of neuronally controlled functions of the intestine persist after I/R. The present study was designed to investigate the time course of damage to neurons and the selectivity of the effect of I/R damage for specific types of enteric neurons. A branch of the superior mesenteric artery supplying the distal ileum of anesthetised guinea pigs was occluded for 1 h and the animals were allowed to recover for 2 h to 4 weeks before tissue was taken for the immunohistochemical localization of markers of specific neuron types in tissues from sham and I/R animals. The dendrites of neurons with nitric oxide synthase (NOS) immunoreactivity, which are inhibitory motor neurons and interneurons, were distorted and swollen by 24 h after I/R and remained enlarged up to 28 days. The total neuron profile areas (cell body plus dendrites) increased by 25%, but the sizes of cell bodies did not change significantly. Neurons of type II morphology (intrinsic primary afferent neurons), revealed by NeuN immunoreactivity, were transiently reduced in cell size, at 24 h and 7 days. These neurons also showed signs of minor cell surface blebbing. Calretinin neurons, many of which are excitatory motor neurons, were unaffected. Thus, this study revealed a selective damage to NOS neurons that was observed at 24 h and persisted up to 4 weeks, without a significant change in the relative numbers of NOS neurons.

Effects of Ischemia and Reperfusion on P2X(2) Receptor Expressing Neurons of the Rat Ileum Enteric Nervous System

Purpose We investigated the effects of ischemia/reperfusion in the intestine (I/R-i) on purine receptor P2X(2)-immunoreactive (IR) neurons of the rat ileum. Methods The superior mesenteric artery was occluded for 45 min with an atraumatic vascular clamp and animals were sacrificed 4 h later. Neurons of the myenteric and submucosal plexuses were evaluated for immunoreactivity against the P2X(2) receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT), calbindin, and calretinin. Results Following I/R-i, we observed a decrease in P2X(2) receptor immunoreactivity in the cytoplasm and surface membranes of neurons of the myenteric and submucosal plexuses. These studies also revealed an absence of calbindin-positive neurons in the I/R-i group. In addition, the colocalization of the P2X(2) receptor with NOS, ChAT, and calretinin immunoreactivity in the myenteric plexus was decreased following I/R-i. Likewise, the colocalization between P2X(2) and calretinin in neurons of the submucosal plexus was also reduced. In the I/R-i group, there was a 55.8% decrease in the density of neurons immunoreactive (IR) for the P2X(2) receptor, a 26.4% reduction in NOS-IR neuron, a 25% reduction in ChAT-IR neuron, and a 47% reduction in calretinin-IR neuron. The density of P2X(2) receptor and calretinin-IR neurons also decreased in the submucosal plexus of the I/R-i group. In the myenteric plexus, P2X(2)-IR, NOS-IR, ChAT-IR and calretinin-IR neurons were reduced in size by 50%, 49.7%, 42%, and 33%, respectively, in the I/R-i group; in the submucosal plexus, P2X(2)-IR and calretinin-IR neurons were reduced in size by 56% and 72.6%, respectively. Conclusions These data demonstrate that ischemia/reperfusion of the intestine affects the expression of the P2X(2) receptor in neurons of the myenteric and submucosal plexus, as well as density and size of neurons in this population. Our findings indicate that I/R-i induces changes in P2X(2)-IR enteric neurons that could result in alterations in intestinal motility.

Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats

Ogihara CA, Schoorlemmer GHM, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA. Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299: R291-R297, 2010. First published April 21, 2010; doi: 10.1152/ajpregu.00055.2009.-Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. The purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. The day after the last exercise session, the rats were anesthetized with intravenous alpha-chloralose, tracheostomized, and artificially ventilated. The femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (-25 +/- 6 and -30 +/- 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 +/- 8 vs. 24 +/- 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (-20 +/- 4 and -16 +/- 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 +/- 2% vs. 19 +/- 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.

TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION

Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target.

Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway

Innate immune responses against microorganisms may be mediated by Toll-like receptors (TLRs). Intestinal ischemia-reperfusion (i-I/R) leads to the translocation of bacteria and/or bacterial products such as endotoxin, which activate TLRs leading to acute intestinal and lung injury and inflammation observed upon gut trauma. Here, we investigated the role of TLR activation by using mice deficient for the common TLR adaptor protein myeloid differentiation factor 88 (MyD88) on local and remote inflammation following intestinal ischemia. Balb/c and MyD88(-/-) mice were subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). Acute neutrophil recruitment into the intestinal wall and the lung was significantly diminished in MyD88(-/-) after i-I/R, which was confirmed microscopically. Diminished neutrophil recruitment was accompanied with reduced concentration of TNF-alpha and IL-1 beta level. Furthermore, diminished microvascular leak and bacteremia were associated with enhanced survival of MyD88(-/-) mice. However, neither TNF-alpha nor IL-1 beta neutralization prevented neutrophil recruitment into the lung but attenuated intestinal inflammation upon i-I/R. In conclusion, our data demonstrate that disruption of the TLR/MyD88 pathway in mice attenuates acute intestinal and lung injury, inflammation, and endothelial damage allowing enhanced survival.

NITRIC OXIDE MEDIATES LUNG VASCULAR PERMEABILITY AND LYMPH-BORNE IL-6 AFTER AN INTESTINAL ISCHEMIC INSULT

Acute lung injury following intestinal I/R depends on neutrophil-endothelial cell interactions and on cytokines drained from the gut through the lymph. Among the mediators generated during I/R, increased serum levels of IL-6 and NO are also found and might be involved in acute lung injury. Once intestinal ischemia itself may be a factor of tissue injury, in this study, we investigated the presence of IL-6 in lymph after intestinal ischemia and its effects on human umbilical vein endothelial cells (HUVECs) detachment. The involvement of NO on the increase of lung and intestinal microvascular permeability and the lymph effects on HUVEC detachment were also studied. Upon anesthesia, male Wistar rats were subjected to occlusion of the superior mesenteric artery during 45 min, followed by 2-h intestinal reperfusion. Rats were treated with the nonselective NO synthase (NOS) inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) or with the selective inhibitor of iNOS aminoguanidine 1 h before superior mesenteric artery occlusion. Whereas treatment with L-NAME during ischemia increased both IL-6 levels in lymph and lung microvascular permeability, aminoguanidine restored the augmented intestinal plasma extravasation due to ischemia and did not induce IL-6 in lymph. On the other hand, IL-6 and lymph of intestinal I/R detached the HUVECs, whereas lymph of ischemic rats upon L-NAME treatment when incubated with anti-IL-6 prevented HUVEC detachment. It is shown that the intestinal ischemia itself is sufficient to increase intestinal microvascular permeability with involvement of iNOS activation. Intestinal ischemia and absence of constitutive NOS activity leading to additional intestinal stress both cause release of IL-6 and increase of lung microvascular permeability. Because anti-IL-6 prevented the endothelial cell injury caused by lymph at the ischemia period, the lymph-borne IL-6 might be involved with endothelial cell activation. At the reperfusion period, this cytokine does not seem to be modulated by NO.

Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion

Estudo do sistema portal hepático no pato doméstico (Cairina moshata)

Estudou-se o comportamento do sistema portal hepático em 30 patos domésticos, adultos, machos e fêmeas. O sistema apresenta-se constituído por duas veias portais hepáticas: direita e esquerda. A veia portal hepática esquerda é formada por veias gástricas esquerdas (em número de 1 a 2), veias da margem ventral do ventrículo, veia pilórica e veia proventricular caudal. A veia portal hepática direita é formada pela veia mesentérica caudal, veia mesentérica cranial, veia proventrículo-esplênica e veia gastropancreaticoduodenal. A veia mesentérica caudal recebe tributárias do mesorreto, cloaca e junção ileocecocólica. A veia mesentérica cranial recebe tributárias jejunais (em número de 12 a 21) e se anastomosa com a veia mesentérica caudal, formando a veia mesentérica comum. A veia pancreaticoduodenal recebe duas veias gástricas direitas, constituindo assim a veia gastropancreaticoduodenal. A veia proventrículo-esplênica é formada pelas veias proventriculares dorsal e direita e pelas veias esplênicas.