Phospholipid Remodeling and Eicosanoid Signaling in Colon Cancer Cells.

Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

Aislamiento de sustancia tensioactiva de pulmones de cerdo: análisis químico y evaluación in vitro e in vivo de la actividad de superficie / Isolation of a pulmonary surfactant in pig lungs. Chemical analysis and in vitro and in vivo evaluation of surface activity

Introducción. Se aisló una sustancia tensioactiva pulmonar (STP) de porcino para su eventual uso en humanos. Se presenta el análisis químico, estudio in vitro de la actividad de superficie y la efectividad in vivo en un modelo animal. Material y métodos. Se obtuvo STP de lavados bronquiales de pulmón porcino mediante centrifugación y solubilidad diferencial. La actividad de superficie se midió con un surfactometro de burbuja pulsátil. Se evaluó in vivo con cobayos adultos deficientes de STP. Resultados. La concentración de proteínas fue menor a 1 mg/100 mg de fosfolípidos. Este extracto mostró: histéresis amplia, Ymin cercana a 0 mN/m, Ymax de 38 mN/m, índice de estabilidad de 1.98. En el cobayo aumentó la PaO2 a más del doble con disminución significativa de la hipercarbia. Conclusiones. El tensioactivo aislado mostró una magnífica actividad de superficie in vitro y mejoró significativamente la hipoxia e hipercarbia en animales sometidos a lavados pulmonares

Espectro neurológico del lupus eritematoso y su asociación con anticuerpos antifosfolípido / Neurologic symptoms of lupus and antiphospholipid antibodies

En el presente estudio se analizan las manifestaciones neuropsiquiátricas en 36 niños con lupus eritematoso sistémico (LES): 12 presentaban convulsiones, 10 cefalea frecuente y 10 hemiparesia. A 18 se les hizo electroencefalograma (EEG) que mostró encefalopatía difusa en 12. La tomografía cerebral (TAC) se hizo en nueve, encontrando vasculitis en cinco. En siete de estos niños se determinó los anticuerpos antifosfolípidos. No hubo diferencia alguna en las manifestaciones clínicas y los resultados del EEG y TAC entre los niños con AcAFL positivos y negativos

Structural features of LPPG and related compounds isolated from Trypanosoma cruzi trypomastigotes

A hydrophobic fraction isolated from trypomastigotes of Trypanosoma cruzi is being characterized using immunological and chemical techniques. The lipopeptidophosphoglycan (LPPG) was identified in this fraction since it gave a positive reaction with anti-LPPG rabbit serum and had similar structural features such as the presence of ceramide as the lipid moiety, furanoic galactose, and a glycan moiety consistent with that obtained from an authentic sample of epimastigote LPPG, as judged by thin-layer chromatography. Furthermore, the hydrophobic fraction contained other glycolipids with different structural features. The lipid moiety of these compounds is alkylglycerol rather than a ceramide, the carbohydrate chain appears to be less complex than that in LPPG and no reactivity was observed towards an anti-LPPG serum

Molecular approaches to diagnosis of Chagas' disease: use of defined antigens and a target ribosomal RNA sequence

We evaluated the performance of two defined antigens in the serological diagnosis of Chagas' disease. One of them is a recombinant protein named B13 isolated from a genomic library of Trypanosoma cruzi in the expression vector lambda gtll. We show that the gene corresponding to B13 is conserved in the evolutive stages of the two ®polar® strains of T. cruzi. The protein epitopes cloned in B13 are represented in 140 kDa, 116 kDa and 35 kDa polypeptides of trypomastigotes. The other antigen chosen for serodiagnosis is a lipopeptidophosphoglycan (LPPG). This glycoconjugate is also widely distributed in T. cruzi strains. The use of a rabbit serum to LPPG allowed the demonstration that this molecule bears epitopes in common to LPPG-like components and to 80-90 kDa glycoproteins of trypomastigotes. Both B13 and LPPG were evaluated in serodiagnosis by ELISA and RIA using a panel of normal human, Chagasic and Leishmaniasis sera. It was observed that B13 presents high sensitivity and specificity for Chagasic sera. For LPPG it was also concluded that this reagent discriminates between individuals infected and non-infected with T. cruzi. A heterogeneity in the level of antibodies to LPPG in Chagasic patients was detected. No correlation was found between the clinical form of Chagas' disease and the preferential reactivity to B13 or LPPG. We also report preliminary studies towards the characterization of a 100 bp sequence of the 24S alpha rRNA as a target for DNA-based detection systems for diagnosis. We show that polymerase chain reaction of total DNA of different trypanosomatids lead to the specific amplification of a 100 bp fragment only for T. cruzi. Northern blots confirmed the presence of the target region in the mature 24S alpha rRNA. Titration experiments based on the direct amplification of RNA with Taq DNA polymerase allowed the detection of 50 parasites. Studies are in progress to increase the sensitivity of the proposed system

Lupus anticoagulant. A report of 8 cases.

Eight cases with lupus anticoagulants (LA) were diagnosed over the last five years (1984-88). Of these, three were established cases of systemic lupus erythematosus (SLE), where bad obstetric history (2 cases) and recurrent deep venous thrombosis (DVT--1 case) prompted execution of laboratory tests for LA. In the remaining 5 cases, there was no clinical evidence of SLE. However, one case developed laboratory findings suggestive of SLE at a later date. One of these 5 patients was referred for unexplained abnormality in partial thromboplastin time (K). Three had recurrent abortions (one with additional history of DVT) while one had DVT with raised PTT (K). The clinical findings and laboratory tests by which lupus anticoagulants can be diagnosed have been discussed.

Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus erythematosus

Isotipos de imunoglobulinas (IgG e IgM) de proteína básica de mielina (PBM), cerebrosídeos (CER), gangliosídeos (GANG) e cardiolipina (CARD) foram investigados em amostras de líquido cefalorraquidiano (LCR) de 33 pacientes com esclerose múltipla (EM), 18 com síndrome de Guillain-Barré (SGB), e 30 com lúpus eritematoso sistêmico (LES). Pacientes com EM revelaram concentraçöes positivas e significantes para IgG-PBM em 51,5% (p<0,05), IgM-PBM em 18,2%, IgG-CARD em 46,2%; CER e GANG foram detectados em cerca de 20% dos pacientes. A avaliaçäo dos isotipos de imunoglobulinas no soro de pacientes com EM foi positiva em 20,6% para IgF-PBM e 53,0% para IgM-PBM. No LCR dos pacientes com SGB a análise mostrou-se positiva em 56,3% para IgG-PBM (p<0,05), 53% para IgM-PBM, 38,5% para IgG-CER e 23% para IgM-CER, 50% para IgG-CARD e 31% para IgM-GANG. Os isotipos avaliados no soro de 14 pacientes com SGB foram positivos em 18,8% para IgG-PBM e 56,3% para IgM-PBM (p<0,05). No LCR, 50% dos pacientes com LES revelaram positividade para IgG-CARD e 24,1% para IgG-PBM. Os autores acreditam que a presença de anticorpos antifosfolípides seja conseqüente a epifenômeno imune, embora sua presença possa manter e perpetuar o evento imune intrínseco a essas doenças

Anticoagulante lúpico e gestaçäo / Lupus anticoagulant and pregnancy

O anticoagulante lúpico parece ser um anticorpo (usualmente IgG, mas pode ser IgM) que prolonga a coagulaçäo de fosfolipídios por ligar-se a um locus de um antígeno determinante na porçäo fosfolipídica da protrombinase. O anticoagulante prolonga todos os testes de coagulaçäo dependentes dos fosfolipídios, prolongando o tempo de tromboplastina parcial ativado e o tempo da protrombina. O anticoagulante näo é associado com sangramento, mas com trombose. Os testes para anticoprpos antifosfolipídicos podem beneficiar na identificaçäo de mulheres com recorrências de perdas fetais, retardo de crescimento intra-útero, prê-eclâmpsia, hematoma subcorial e hemorragia inexplicável na gestaçäo. O tratamento consiste na supressäo da atividade do anticorpo pela imunossupressäo, prevenindo o risco de tromboembolismo e insuficiência placentária pela heparinoterapia e/ou associaçäo de ácido acetilsalicílico e dipidamol. Inclui também a corticoterapia, azatioprina, ciclofosfamida, imunoglobina intravenosa. Esta condiçäo hematológica com bases imunológicas e obstétricas requer um trabalho multidisciplinar envolvendo indivíduos da área obstétrica, medicina interna, hematológica e imunológica para o diagnóstico e manejo da grávida e seu feto

Antyphospholipid antibodies in syphilis

1. An enzyme-linked immunosorbent assay was used to determine the phospholipid specificity of antibodies in sera from 35 syphilis patients. 2. Based on the cross-reaction obtained aginst a mixture of cardiolipin, phosphatidylcholine and holesterol that is standard for flocculation tests according to the Venereal Disease Research Laboratory (CECON, Säo Paulo, Brazil), all 35 patients tested positive for antibodies of the IgG class whereas 13 (37%) also had IgM antibodies for the same mixture of lipids. IgG antibodies to cardiolipin were demonstrated in 2 patients (6%) and IgM antibodies in 5 (15%). Significant levels of IgG anti-phosphatidylcholine were detected in 3 patients (9%) and IgM antibodies in 4(11%). IgG anti-phosphatidylethanolamine antibodies were found in 1 patient (3%) and IgM antibodies in 3(9%). Antibody binding to cardiolipin plus cholesterol or cardiolipin plus phosphatidycholine was as effective as when the standard mixture of all 3 lipids was used. 3. A comparison with serum from systemic lupus erythematosus patients and inhibition studies using liposomes o cardiolipin or the mixture of 3 lipids suggests that there are at least 3 groups of anticardiolipin antibodies