Variantes Genéticas Pró-Trombóticas como (Improváveis?) Factores de Risco para as Grandes Crises Vaso-Oclusivas na Drepanocitose

CONTEXTO: A drepanocitose é uma anemia hemolítica hereditária com características pró-adesivas, pró-inflamatórias e pró-coagulantes, incluindo alterações na hemostase e activação da cascata da coagulação. PLANO DO ESTUDO: Neste estudo analisaram-se, em 140 drepanocíticos africanos e 126 indivíduos sem hemoglobina S também de origem africana, variantes genéticas polimórficas em quatro loci envolvidos na coagulação (F2 20210G>A e F5 R506Q), na fibrinólise (PAI-1 5G>4G), ou no metabolismo da homocisteína (MTHFR 677C>T). Estratificaram-se os pacientes em dois grupos de acordo com a ocorrência ou não de, pelo menos, uma complicação vaso-oclusiva (CVO) grave até à data da sua participação no estudo. RESULTADOS: Não se observou uma associação estatisticamente significativa entre a ocorrência de uma CVO grave e a herança do alelo predisponente à trombose, 4G no locus PAI-1 ou 677T no locus MTHFR. Nenhum drepanocítico apresentava os alelos F2 20210A ou F5 506Q (factor V Leiden). Visando excluir a possibilidade de que genuínas diferenças inter-grupos fossem mascaradas pela presença de indivíduos mais jovens no grupo sem-CVO, dividiu-se este num sub-grupo de pacientes mais novos e num sub-grupo de pacientes cuja idade não diferia significativamente do grupo com-CVO grave. Mesmo assim, não foi encontrada associação significativa. No entanto, pode observar-se, no grupo de doentes com o alelo PAI-1 4G (cuja expressão resulta numa diminuição da actividade fibrinolítica), uma tendência (OR=1,6) para um risco acrescido de CVO. Esta tendência era ligeiramente maior (OR=2,1) se se considerasse apenas a CVO síndrome torácica aguda. CONCLUSÕES: O alelo 4G no promotor do PAI-1 poderá ser um factor de risco para CVO na drepanocitose, uma hipótese a testar numa série maior de doentes, idealmente oriunda de uma população homogénea e com alta prevalência de drepanocitose.

Transplant Glomerulopathy: Clinico-Pathologic Features

Transplant glomerulopathy is a sign of chronic kidney allograft damage. It has a distinct morphology and is associated with poor allograft survival. We aimed to assess the prevalence and clinic-pathologic features of transplant glomerulopathy, as well as determine the functional and histological implications of its severity. We performed a single-centre retrospective observational study during an eight-year period. Kidney allograft biopsies were diagnosed and scored according to the Banff classification, coupled with immunofluorescence studies. The epidemiology, clinical presentation, outcomes (patient and graft survival) and anti-HLA alloantibodies were evaluated. Transplant glomerulopathy was diagnosed in 60 kidney transplant biopsies performed for clinical reasons in 49 patients with ABO compatible renal transplant and a negative T-cell complement dependent cytotoxicity crossmatch at transplantation. The estimated prevalence of transplant glomerulopathy was 7.4% and its cumulative prevalence increased over time. C4d staining in peritubular capillaries (27.6%) was lower than the frequency of anti-HLA antibodies (72.5%), the majority against both classes I and II. Transplant glomerulopathy was associated with both acute (mainly glomerulitis and peritubular capillaritis) and chronic histologic abnormalities. At diagnosis, 30% had mild, 23.3% moderate and 46.7% severe transplant glomerulopathy. The severity of transplant glomerulopathy was associated with the severity of interstitial fibrosis. Other histological features, as well as clinical manifestations and graft survival, were unrelated to transplant glomerulopathy severity.

Intestinal helminthiases in Ecuador: the relatíonship between prevalence, genetic, and socioeconomic factors

Prevalence of infection with the intestinal helminths, Ascaris lumbricoides, Trichuris trichiura, Ancylostoma duodenale and Strongyloides stercoralis was examinedin 632 residents of communities in Esmeraldas province of Ecuador. These communities were divided into two groups according to area of habitation which reflected different socioeconomic circumstances. Attempts were made to correlate infection status with race and ABO blood group phenotype. The racial groups included blacks, Chachi amerindians, and mixed-race mestizos. Greater prevalences of infection were seen in the area oflower socioeconomic status. No racial or blood group associations with helminth infection were seen controlling for socioeconomic status.

Soroprevalência da infecção por Helicobacter pylori em crianças de diferentes níveis sócio-econômicos em Porto Velho, Estado de Rondônia

O estudo investigou a soroprevalência de infecção pelo Helicobacter pylori em 200 (subdivididas em 2 grupos) crianças da Cidade de Porto Velho, Rondônia. A prevalência da soropositividade variou consideravelmente de acordo com o nível sócio-econômico, onde 51% das crianças de baixo nível e 24% de classe média eram positivas. As características da população infantil relacionadas ao sexo, raça e dieta alimentar não representaram fatores de risco para a aquisição da infecção; porém, a maioria das infectadas pertencia à faixa etária de cinco ou mais anos, independente do nível sócio-econômico. A distribuição fenotípica dos grupos sanguíneos ABO, entre os indivíduos infectados e não infectados, mostrou4 que a sororeatividade ao Helicobacter pylori foi maior entre as crianças do grupo sanguíneo O, sugerindo que há uma maior susceptibilidade genética destas crianças para a infecção pelo Helicobacter pylori.

A spectrophotometry based blood typing device

Blood typing is a crucial step before any blood transfusion. However, sometimes in emergency situations there is no time to determine the blood of the patient beforehand. In this cases, O negative blood type is administered, which has a lesser incompatibility risk to the patient. Nowadays, the “gold standard” blood typing devices cannot be used in emergency situations due to their high response time (about 30 minutes). This paper reports a blood typing device that determines the ABO and Rh human phenotypes. This device is fast (response time – 5 min), low-cost, and portable. Characteristics that make it suitable to be used in emergency situations, contributing to a higher efficiency and quality in healthcare.

Estudios de proteínas y glicoconjugados en diferentes estados patológicos: Procesos demielinizantes y diarreas provocadas por bacterias toxigénicas

1) Estudios bioquímicos, inmunológicos e histológicos en encefalomielitis alérgica experimental (EAE): comprende el análisis de las diferentes alteraciones que ocurren en SNC durante el desarrollo de esta patología experimental. Se tratará de acotar los diferentes procesos que participan en la inducción activa de la enfermedad por inyección de antígenos de mielina, pasiva por sensibilización con diferentes poblaciones linfocitarias provenientes de animales enfermos, posterior recuperación o supresión de las diferentes alteraciones neuropatológicas por inducción de procesos de tolerancia inmunológica con antígenos mielínicos o sinaptosomales. Teniendo en cuenta la reacción inmunológica cruzada previamente descripta entre la proteína básica de mielina y sinapsina, se continuará con la caracterización de las poblaciones de linfocitos T que reconocen ambas proteínas por ensayos in vitro e in vivo. 2) Mecanismos de acción de enterotoxinas bacterianas: se estudia la posible participación de glicoconjugados (glicolípidos, mucinas y glicoproteínas de membrana) con actividad de grupo sanguíneo ABO (H) en relación al mecanismo de acción de algunas enterotoxinas bacterianas como toxina colérica y toxinas lábiles al calor producidas por E. coli aisladas de cepas que colonizan intestino humano (LTh) o porcino (LTp). Los objetivos específicos son extender nuestros estudios previos al intestino humano porque estas patologías afectan al hombre y además las estructuras químicas de los glicoconjugados en estudio son más variadas y están mejor dilucidades que en las especies animales anteriormente estudiadas (cerdo, conejo). Además, se planea realizar ensayos in vitro mediante la técnica de segmentos ligados de intestino de conejo con el objeto de estudiar si los glicolópidos y glicoproteínas de membrana con actividad de grupo sanguíneo ABH se comportan como receptores funcionales de alguna de las toxinas.

Histomorfologia do órgão acessório de perfuração de Thais haemastoma (Mollusca, Gastropoda)

Os representantes da família Thaididae são organismos predadores de outros moluscos, perfurando suas conchas pela ação alternada de secreção oriunda do "Accessory Boring Organ" (ABO) e por raspagem através da rádula. Nesta família, o ABO está localizado na porção ventral mediano-anterior do pé. Os animais examinados neste estudo foram coletados na praia do Futuro, Fortaleza, em seguida levados ao laboratório para fixação e posterior tratamento histológico rotineiro. A porção glandular do ABO de Thais haemastoma (Linnaeus, 1758) se encontra alojada em uma cavidade circundada pela musculatura do pé e apresentando um ducto excretório que a comunica com o meio externo. Esta cavidade é revestida por um epitélio cilíndrico simples separando a porção glandular deste órgão do músculo pedioso, sendo contínuo com o epitélio de revestimento do ducto excretório. Subjacente a este tecido foi visualizado um tecido conjuntivo frouxo. A região glandular do ABO da espécie apresenta um formato discoidal com superfície irregular devido à presença de reentrâncias em direção à porção central da glândula. O epitélio glandular pseudoestratificado com células cilíndricas e ciliadas reagiu negativamente aos testes histoquímicos. Abaixo do epitélio, foi observado um tecido conjuntivo frouxo de sustentação.

Decay accelerating factor (DAF) as the host antigen with protective activity to complement killing of schistosomula

The acquisition of host antigens by Schistosoma mansoni was studied by evaluating the resistance of schistosomula to the complement attack mediated by lethal antibody. Schistosomula cultured for 24 hours with intact human erythrocytes (N-HuE) or ghosts of any type of ABO or Rh blood group, showed a marked resistance to complement damage. Sheep red blood cells, pronase-treated N-HuE or erythrocytes from patients with paroxysmal nocturnal hemoglobinuria, which are complement-sensitive cells, were unable to protect schistosomula. Schistosomula protected by N-HuE became again susceptible to complement killing after incubation with a monoclonal antibody anti-DAF. These results indicate that, in vitro, host DAF from N-HuE can be acquired by schistosomula surface in a biological active form that protects the parasite from the complement lesion.

Natural lectin activity in the haemolymph of Panstrogylus megistus (Heteroptera: Reduvidae)

The haemolymph of Panstrongylus megistus showed a natural lectin activity for a wide range of vertebrate erythocytes. Agglutination was observed against all vertebrate erythrocytes tested (human ABO, duck, rabbit, mouse, sheep, chicken and cow). Cow erythrocytes showed the lowest titre. Concerning human erythrocytes, the lectin activity was similar in the types A+,B+ and AB+ while the highest activity was observed in the type O+. Determination of minimal inhibitory concentrations was carried out with human erythrocytes type O+. Agglutination was inhibited by several carbohydrates (rhamnose. D-galatose, raffinose, D-lactose and D-fucose). Rhamnose wasreported as the strongest inhibitor (0.78mM). The results suggest the presence of more than one lection in the haemolymph of P. megistus.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.

Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement

Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE) whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF) , a 70 kDa glycoprotein attached to the membrane of NHue by a GPI anchor. IgG2a mAb anti-human DAF (IA10) immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vtro. Incubationof schistosomula with erytrocytes from patients with paroxsimal nocturnal hemoglobinuria (PNHE) or SRBC, wich are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polipeptide(s) present on the surface of the worm.

Aspectes geomètrics i dinàmics de transformacions racionals planes

Donada una aplicació racional en una varietat complexa, Bellon i Viallet van definit l’entropia algebraica d’aquesta aplicació i van provar que aquest valor és un invariant biracional. Un invariant biracional equivalent és el grau asimptòtic, grau dinàmic o complexitat, definit per Boukraa i Maillard. Aquesta noció és propera a la complexitat definida per Arnold. Conjecturalment, el grau asimptòtic satisfà una recurrència lineal amb coeficients enters. Aquesta conjectura ha estat provada en el cas polinòmic en el pla afí complex per Favre i Jonsson i resta oberta en per al cas projectiu global i per al cas local. L’estudi de l’arbre valoratiu de Favre i Jonsson ha resultat clau per resoldre la conjectura en el cas polinòmic en el pla afí complex. El beneficiari ha estudiat l’arbre valoratiu global de Favre i Jonsson i ha reinterpretat algunes nocions i resultats des d’un punt de vista més geomètric. Així mateix, ha estudiat la demostració de la conjectura de Bellon – Viallet en el cas polinòmic en el pla afí complex com a primer pas per trobar una demostració en el cas local i projectiu global en estudis futurs. El projecte inclou un estudi detallat de l'arbre valoratiu global des d'un punt de vista geomètric i els primers passos de la demostració de la conjectura de Bellon - Viallet en el cas polinòmic en el pla afí complex que van efectuar Favre i Jonsson.

The association of genetic markers and malaria infection in the Brazilian Western Amazonian region

Almost all individuals (182) belonging to an Amazonian riverine population (Portuchuelo, RO, Brazil) were investigated for ascertaining data on epidemiological aspects of malaria. Thirteen genetic blood polymorphisms were investigated (ABO, MNSs, Rh, Kell, and Duffy systems, haptoglobins, hemoglobins, and the enzymes glucose-6-phosphate dehydrogenase, glyoxalase, phosphoglucomutase, carbonic anhydrase, red cell acid phosphatase, and esterase D). The results indicated that the Duffy system is associated with susceptibility to malaria, as observed in other endemic areas. Moreover, suggestions also arose indicating that the EsD and Rh loci may be significantly associated with resistance to malaria. If statistical type II errors and sample stratification could be ruled out, hypotheses on the existence of a causal mechanism or an unknown closely linked locus involved in susceptibility to malaria infection may explain the present findings.

Genetic Studies in Cabo Verde Archipelago

Blood group of ABO and MN systems, hemoglobin and haptoglobin were studied among immigrants from Cabo Verde working in Portugal. The origin, admixture and differentiation of the of populations of the archipelago are discussed.