Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

OBJETIVO: Avaliar a atividade da acetil-hidrolase do fator ativador de plaquetas (PAF-AH) e sua relação com variáveis clinicodemográficas, com o controle metabólico, os níveis de apolipoproteínas A e B e a suscetibilidade da lipoproteína de baixa densidade (LDL) à oxidação in vitro em pacientes com DM tipo 1 (DM 1). MÉTODOS: Foram avaliados 42 pacientes com DM1 (27 mulheres) e 48 não-diabéticos (16 mulheres), pareados por sexo, idade e índice de massa corporal (IMC). Os exames realizados foram: glicemia de jejum (GJ) e pós-prandial (GPP), lipidograma, ácido úrico (AU), hemoglobina glicosilada (HbA1c) e coeficiente de oxidação da lipoproteína de baixa densidade (LDL) por espectrofotometria. A análise da atividade da PAF-AH foi realizada por espectrofotometria (Cayman Chemical). RESULTADOS: A análise da atividade da PAF-AH mostrou haver maior atividade enzimática nos pacientes com DM 1 do que nos não-diabéticos (0,0150 ± 0,0051 versus 0,0116 ± 0,0041; p < 0,001). Nos pacientes com DM 1, encontramos correlação direta entre a atividade da PAF-AH e a idade e a LDL, e inversa entre a PAF-AH e a HbA1c e a lipoproteína de alta densidade (HDL). CONCLUSÃO: A PAF-AH, na amostra estudada, apresentou maior atividade nos pacientes com DM 1, fator que pode estar relacionado ao maior risco de desenvolver doenças cardiovasculares apresentados por portadores dessa doença. Ainda são necessários novos estudos para avaliar a real participação dessa enzima no risco de desenvolvimento das doenças ateroscleróticas nos pacientes com DM 1.

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.

The rational search for natural neolignans

A rational method of search for natural neolignans of desired structures is outlined. This involves consultation of a collection of chemical profiles of plant families. The profiles are assembled considering the biosynthetic class (in the present case lignoids), subclass (neolignans), structural types (neolignan skeleta) and relative frequency of substitutional derivatives belonging to each type (known compounds). The method is of course applicable to ani class of natural products. Its use in the case of neolignans is here selected as an exemple in view of the recently discovered antagonism towards PAF of kadsurenone, a representative of this subclass of phytochemicals. Application of the chemical profiles to phylogenetic studies is illustrated.

Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin

The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibt eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo.

A role for lymphocytes and cytokines on the eosinophil migration induced by LPS

In the present work we review the existing evidence for a LPS-induced cytokine-mediated eosinophil accumulation in a model of acute inflammation. Intrathoracic administration of LPS into rodents (mice, rats or guinea pigs) induces a significant increase in the number of eosinophils recovered from the pleural fluid 24 hr later. This phenomenon is preceded by a neutrophil influx and accompanied by lymphocyte and monocyte accumulation. The eosinophil accumulation induced by LPS is not affected by inhibitors of cyclo or lipoxygenase nor by PAF antagonists but can be blocked by dexamethasone or the protein synthesis inhibitor cycloheximide. Transfer of cell-free pleural wash from LPS injected rats (LPS-PW) to naive recipient animals induces a selective eosinophil accumulation within 24 hr. The eosinophilotactic activity present on the LPS-PW has a molecular weight ranging between 10 and 50 kDa and its effect is abolished by trypsin digestion of the pleural wash indicating the proteic nature of this activity. The production of the eosinophilotactic activity depends on the interaction between macrophages and T-lymphocytes and its effect can not be blocked by anti-IL-5 monoclonal antibodies. Accumulated evidence suggest that the eosinophil accumulation induced by LPS is a consequence of a eosinophilotactic cytokine produced through macrophage and T-cell interactions in the site of a LPS-induced inflammatory reaction.

Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE) type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF) and leukotriene B4 (LTB4) in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP) and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP) has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor) nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

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.

Search for a platelet-activating factor receptor in the Trypanosoma cruzi proteome: a potential target for Chagas disease chemotherapy

Chagas disease (CD) causes the highest burden of parasitic diseases in the Western Hemisphere and is therefore a priority for drug research and development. Platelet-activating factor (PAF) causes the CD parasite Trypanosoma cruzi to differentiate, which suggests that the parasite may express PAF receptors. Here, we explored the T. cruzi proteome for PAF receptor-like proteins. From a total of 23,000 protein sequences, we identified 29 hypothetical proteins that are predicted to have seven transmembrane domains (TMDs), which is the main characteristic of the G protein-coupled receptors (GPCRs), including the PAF receptor. The TMDs of these sequences were independently aligned with domains from 25 animal PAF receptors and the sequences were analysed for conserved residues. The conservation score mean values for the TMDs of the hypothetical proteins ranged from 31.7-44.1%, which suggests that if the putative T. cruzi PAF receptor is among the sequences identified, the TMDs are not highly conserved. These results suggest that T. cruzi contains several GPCR-like proteins and that one of these GPCRs may be a PAF receptor. Future studies may further validate the PAF receptor as a target for CD chemotherapy.

GLICEROFOSFOLIPÍDIOS SINTÉTICOS PARA USO COMO ADITIVO BIOCIDA EM TINTAS ANTI‑INCRUSTANTE

AbstractThis paper presents a technological innovation that uses a subclass of glycerophospholipids as a booster biocide in antifouling paint. These glycerophospholipid PAF-analogs are economically and environmentally viable compounds because they are synthesized from a metal-free raw material source-soybean lecithin. The synthesis, which involves transesterification followed by an alkylation reaction, produced a mixture of glycerophospholipids that were characterized by mass spectrometry. Evaluation of the antifouling performance with field tests showed that the replacement of ordinary halogenated booster biocide with the synthesized product gave a better efficiency and an exceptional antifouling activity with a significant reduction in the coverage of the fouling macro-organisms.

Racionalização do uso de força motriz em fábrica de ração

A falta de investimento no setor energético, aliada à sazonalidade de recursos naturais necessários para a geração de energia hidroelétrica, faz da racionalização do uso de energia elétrica uma ferramenta de apoio imprescindível para o crescimento do País. A ração animal pode representar entre 70 e 80% do custo de produção da criação de animais. Sendo assim, é importante o estudo da racionalização do uso de energia em processos que utilizam intensivamente força motriz, tais como as fábricas de ração. Na fábrica de ração estudada, os motores elétricos são utilizados principalmente para moagem e mistura de granulados e transporte. Com o objetivo de racionalizar o uso da energia elétrica, foi realizado estudo de adequação de força motriz dos equipamentos da fábrica de ração da Indústria Pif Paf Alimentos. O índice de carregamento médio dos motores elétricos estudados foi de 48,6%. O potencial estimado total de economia com energia elétrica anual, utilizando-se sempre da melhor opção de adequação de força motriz foi de R$ 24.426,50 ao ano (23,9%). Para que essas medidas sejam efetivadas, devem-se adequar também: (i) as exigências elétricas do circuito, como ajuste de relés e escolha de fusíveis; (ii) o horário de funcionamento, e (iii) necessidade de implantação de sistema de armazenamento de ração.

Retocolectomia total e anastomose íleo-anal com reservatório ileal: experiência de 16 anos

O reservatório ileal pélvico tem sido a melhor opção cirúrgica para a retocolite ulcerativa (RCU) e polipose adenomatosa familiar (PAF). Desde 1983 esta técnica vem sendo empregada, e o objetivo deste trabalho é apresentar revisão desta casuística, analisando seus resultados e seus pontos controversos. Setenta e três pacientes, com média de idade de 34,6 (13-63) anos e com predomínio do sexo feminino (42 pacientes, 56,7%) se submeteram ao procedimento para tratamento de RCU (46 pacientes - 63,0%) e PAF(27 - 37,0%). Foram utilizadas as seguintes variantes técnicas: em S, de grande tamanho e ramo eferente longo (oito); em S pequeno e ramo eferente reduzido (22); em "dupla câmara" (20); em J (23). Todos os procedimentos foram seguidos da construção de ileostomia de proteção. De 1993 em diante, todos os pacientes tiveram a arcada do colo direito preservada. Setenta pacientes têm pelo menos um ano de pós-operatório e 61 têm dois anos ou mais com média de 7,01 (1-16) anos. Foram consideradas complicações precoces aquelas que ocorreram até o 30º dia de pós- operatório e tardias, após esse tempo. Resultados funcionais foram analisados após um ano do fechamento da ileostomia. Ocorreram 35 complicações precoces em 22 pacientes e 39 complicações tardias em 35 pacientes. Vinte e cinco pacientes não apresentaram complicações. As principais complicações foram: obstrução intestinal (19,1 %), fistulizações cutâneas, com vagina ou trato urinário (10,9%), isquemia de reservatório (parcial ou total), (9,5%), e ileíte do reservatório (pouchitis) (6,8%). Nove pacientes (12,3%) têm ileostomia funcionante, sendo que sete pacientes têm ainda o reservatório mantido no lugar e dois tiveram-no ressecado. A mortalidade diretamente relacionada ao procedimento foi em dois pacientes, mas outros quatro pacientes evoluíram tardiamente ao óbito, por causas como desnutrição crônica e tumor de cerebelo. Em conclusão, apesar da morbidade e da existência ainda de questões controversas, as perspectivas tardias têm sido animadoras e têm estimulado a indicação deste tipo de procedimento.

Incidência de fístulas digestivas nos ferimentos toracoabdominais

Os ferimentos penetrantes localizados na transição toracoabdominal (FTA), além da dificuldade diagnóstica, merecem especial atenção em relação à conduta adotada para o controle das complicações abdominais. Os autores analisaram 110 pacientes atendidos na Disciplina de Cirurgia do Trauma do Departamento de Cirurgia da UNICAMP, de 1988 a 1998, apresentando ferida penetrante toracoabdominal e submetidos à laparotomia exploradora com drenagem pleural fechada. As fístulas digestivas foram estudadas quanto à incidência, ao tratamento e à evolução pós-operatória. Do total de pacientes, 91 (82,7%) eram do sexo masculino e 19 (17,3%) do sexo feminino. A faixa etária situou-se entre 13 e 63 anos. Os FTA foram causados por projétil de arma de fogo (PAF) em 60 (54,5%) casos e por arma branca (FAB) em 50 (45,5%). As fístulas digestivas ocorreram em seis (5,4%) dos pacientes estudados, sendo quatro (3,6%) casos de fístula pancreática, um (0,9%) de fístula gástrica e um (0,9%) de fístula biliar, todos tratados de maneira conservadora, apresentando evolução favorável com resolução espontânea.