The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

A major goal in the treatment of acute ischemia of a vascular territory is to restore blood flow to normal values, i.e. to "reperfuse" the ischemic vascular bed. However, reperfusion of ischemic tissues is associated with local and systemic leukocyte activation and trafficking, endothelial barrier dysfunction in postcapillary venules, enhanced production of inflammatory mediators and great lethality. This phenomenon has been referred to as "reperfusion injury" and several studies demonstrated that injury is dependent on neutrophil recruitment. Furthermore, ischemia and reperfusion injury is associated with the coordinated activation of a series of cytokines and adhesion molecules. Among the mediators of the inflammatory cascade released, TNF-alpha appears to play an essential role for the reperfusion-associated injury. On the other hand, the release of IL-10 modulates pro-inflammatory cytokine production and reperfusion-associated tissue injury. IL-1beta, PAF and bradykinin are mediators involved in ischemia and reperfusion injury by regulating the balance between TNF-alpha and IL-10 production. Strategies that enhance IL-10 and/or prevent TNF-alpha concentration may be useful as therapeutic adjuvants in the treatment of the tissue injury that follows ischemia and reperfusion.

Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase

Platelet-activating factor (PAF) is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation.

Manejo odontológico de pacientes con enfermedades hemorrágicas y terapia anticoagulante / Dental management of patients with hemorrhagic diseases and anticoagulant therapy

La historia clínica es fundamental en el manejo de cualquier tipo de pacinetes, los síntomas y signos que pueden sugerir enfermedad hemorrágica pueden ser de dos tipos: los que se ven más frecuentes en las alteraciones de los factores de coagulación y aquellos que son más comunes en trastornos de la hemostasia primaria, plaquetaria o vasculares y se conocen generalmente como púrpuras o síndrome purpúrico. Las petequias son pequeñas hemorragias capilares, usualmente puntiformes, son típicas en el síndrome purpúrico y suelen ser más intensas y confluentes en los sitios de presión. La equimosis es la infiltración en la piel o mucosas de la sangre extravasada (el típico moretón o cardenal), están usualmente asociadas a petequias en el síndrome purpúrico, pero pueden verse de buen tamaño, en los trastornos de coagulación y síndromes hiperfibrinolíticos. Los hematomas, colección de sangre extravasada en los músculos o tejidos profundos, son más frecuentes en los defectos del sistema de coagulación, como lo es también la hemartrosis, hemorragia intraarticular casi patognomónica de trastorno hereditario severo de la coagulación (hemofilia A y B). El sangramiento purpúrico se caracteriza por hemorragias mucocutáneas (petequia, equimosis, monorragias, hematura o sangramiento digestivo). Usualmente ellas son múltiples, y a veces aparecen después de injurias superficiales, el sangramiento comienza inmediatamente después de la ruptura vascular, todas estas manifestaciones clínicas son importantes que el odontólogo las reconozca con el fin de proporcionar un mejor tratamiento odontológico al paciente con trastornos hemorrágicos y evitar complicaciones no deseadas

Experiments suggesting a role for the platelet-activating factor in hippocampal and amygdala synapses in memory in rats

Platelet-activating factor (1-O-alky1-2-acetyl-sn-glycero-3-phosphocholine, PAF) is present in brain, is released from neurons in culture and, in hippocampal slices, enhances glutamate release and long-term potentiation (LTP) through an action on membrane receptors sensitive to the antagonist, BN 52021. This led to the proposal that PAF may be a retrograde messenger in the genesis of LTP. LTP has been, in turn, proposed as a mechanism of memory. Male Wistar rats were implanted bilaterally with cannulae aimed at the amygdala and the dorsal hippocampus. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5 mA footshock, and tested for retention 24 h later. BN 52021 (0.5 mug) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 min later. The findings support the idea that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala, and further suggest that PAF is involved in the development of this LTP.

Involvement of PAF-acether and eicosanoids in adrenaline-induced pulmonary edema in mice

The participation of platelet-activating factor (PAF,PAF-acether) in a mouse model of pulmonary edema was studied using specific antagonists.Mice were treated before induction of edema with the PAF antagonists BN52021 (10mg/kg, ip), PCA 4248 (10 mg/kg, po) or WEB2170 (10mg/kg, ip),the lipoxygenase inhibitor EP10161 (10 mg/kg,ip),the cyclo-oxygenase inhibitor aspirin (250 mg/kg,po), or with the mixed cyclo-lipoxygenase inhibitor BW755C(50 mg/kg, ip).The test drugs were administered to animals either 30 min (When the ip route was used) or 60 min (when given po) prior to the induction of pulmonary edema.Pulmonary edema was induced by intravenous administration of adrenaline (2 mg/kg). When the lung-body index was usedas thecriterion for comparision between groups,BN52021, PCA4248 and WEB2170 were found to have no significant effect on pulmonary edema. In contrast, EP10161, aspirinand BW755C significantly inhibited pulmonary edemaby 49%,30% and 27%,respectively. The results suggest that arachidonate metabolites are likely to play a major roe in adrenaline-induced pulmonary edema in mice, whereas PAF-acether does not seem to play an important role in this model

Enterolobin induces rat paw oedema independently of PAF-acether

The potential participation of PAF-acether (PAF) on the paw oedema triggered by enterolobin was investigated. Intraplantar injections of enterolobin )5-20 µg/paw) yielded a dose response curve for edema which appeared after 30 min, peaked in the interval between 2-4 h and faded after 24h. The pre-treatment with BN 52021, but not with other PAF antagonists such as PCA 4248 or WEB 2086, significantly blocked enterolobin-induced oedema. To clarify better the discrepant results obtained with the PAF antagonists, desensitization to PAF was performed. The oedema triggered by enterolobin was not modified in paf desensitized animals. It was concluded that the paw inflammation induced by enterolobin does not require PAF mechanism.

Fator ativador de plaquetas (platelet fator - PAF) implicaçoes fisiopatologicas / Platelet activating factor (platelet fator - PAF) physiopathologics implications

O fator de ativaçao de plaquetas (PAF) produzido por diferentes tipos de celulas e considerado um potente mediador de reaçoes como a vasodilataçao, a anafilaxia e a inflamaçao. Sua caractericaçao como um fosfolipidio originario de membrana celular, dependente de fosfolipase A2, ensejou as condiçoes satisfatorias para sua sintese, permitindo tambem a pesquisa de compostos antagonistas que agem em sitios receptivos. O emprego destes compostos em varios modelos experimentais contribuiu decisivamente para o grande volume de informaçoes atualmente disponiveis sobre as açoes biologicas do PAF. No presente trabalho sao revistos aspectos da fisiologia biopatologia do fosfolipidio, com enfase na anafilaxia, inflamaçao, trombose e choque. Referencia especial feita aos resultados obtidos com antagonistas naturais derivados de Ginkgo biloba sobre os eventos fisiologicos renais de escape e taquifilaxia noradrenergicos