O puru-puru da Amazônia (Pinta, Carate, Mal del Pinto etc)

1) "Purú-purú" é uma palavra indígena que quer dizer "pintado" ou "manchado", peculiar à Amazonia Brasileira. Com êsse nome é designada uma dermatose referida entre os selvicolas desde 1774, por Ribeiro Sampaio. Certas tribus, com alta incidência da moléstia passaram a ser cahamadas também "Purú-purús", o mesmo acontecendo com o rio onde habitavam - Rio Purús. 2) A doença existe na bacia do Rio Solimões e seus principais afluentes: Javari, Juruá, Purús, Içá, Japurá, e Negro. Por esses rios, o fóco da dermatose se continua nos países limitrofes com o Brasil: Guianas, Venezuela, Colombia, Perú (Equador) e Bolivia. 3) Desde 1890 essa dermatose foi relacionada à pinta (carate ou mal del pinto) por P. S. de Magalhães, idéa essa depois defendida por Juliano Moreira, Carlos Chagas, Roquete Pinto, Wappeus, O. da Fonseca Filho, Da Matta, Brumpt e outros, baseados na semelhança clínica e na terapêutica. Recentemente (1945), essa provavel identidade das duas dermatoses, recebeu fundamento sorológico de Biocca (que verificou a positividade das reações de Kline e Kahn em doentes de purú-purú), e, pelo presente trabalho, recebe base clínico-epidemio-anatomo-patológica. 4) Sob o ponto de vista clínico, as lesões cutaneas discromicas da moléstia, são de 3 órdens: a) lesões papulo-eritemato-escamosas, isoladas ou não, arredondadas, pruriginosas e de bordos nitidos; b) lesões maculo-escamosas, maiores mais pálidas, ás vezes já mostrando alterações pigmentares na parte central; c) máculas discromod´rmicas, lisas ou ligeiramente escamosas, com maior ou menor alteração pigmentar, as quais assumem diferentes aspéctos, consequentes à hipo - ou hiperpigmentação, variaveis também com a côr do paciente. As colorações predominantes nas manchas, são o branco, o preto e o vermelho, com tonalidades eminentemente variaveis. Embora raramente, nessas extensas dermodiscromias, observa-se superposição de lesões papulo-eritemato-escamosas. O aparecimento dos 3 tipos de leões acima citados, obedece seguramente a um processo evolutivo da dermatose, dando-se na órdem exposta e de acordo com o tempo de doença. Além das lesões discromicas, características da enfermidade, foi observado purido, e infartamento ganglionar. O estado geral dos doentes era bom. A avaliação de anemia e eosinofilia, foi prejudicada pela ocurrência de outros processos mórbidos (malaria e helmintiases). Em 2 pacientes pretos e adultos, havia avançada hiperqueratose palmo-plantar. 5) Sob o ponto de vista epidemiológico, foram feitas as seguintes observações: a) Idade. A dermtose ocorre em tôdas as idades, mais incide principalmente dos 15 aos 29 anos. Tomando um grupo relativamente homogêneo de doéntes de um mesmo local, 53% têm 15 e mais anos de idade. De 36 doentes que deram informações seguras ou aproximadas quanto à idade em que lhes apareceu a doença, verifica-se que 77% já estavam infectados antes dos 15 anos. Em 5 casos, a infecção se deu antes dos 2 anos de idade. b) Sexo. Nos doentes em conjunto, existiam 34 homens e 35 mulheres. Mas, no grupo homogeneo acima citado, havia ligeira predominância do sexo feminino (60.7%). c) Côr ou raça. Foram encontradas as seguintes percentagens: Pretos - 34.8%, brancos - 27.5% índios - 23.2% e mulatos - 14.5%. Essas diferenças não indicam predileção racial. d) Família. A A dermatose é eminentemente familial. Em grupo de 41 doentes, 34 pertenciam a 8 familias. e) Lesão inicial. Contágio. Em 6 casos ainda existia a lesão inicial, chamada "empigem", isolada ou acompanhada de outras lesões semelhantes. De 33 doentes, 26 (78.8%) referiam a lesão inicial nas partes descobertas do corpo (rosto, braços e mãos, pernas e pés), isto é regiões mais sujeitas a pequenos traumas, que servem como "porta de entrada" do treponema. Os AA não acreditam na existência de um vetor. Pensam que o contágio é direto, as condições eficientes e predisponentes do mesmo, coexistindo no domícilio, onde vivem em promiscuidade e falta de higiene, doentes e sadios. Os autores não encontraram treponemas em córtes impregnados de “purú-purú”, tanto de “lesão recente” como de “lesão tardia”. Atribuem o fracasso ao provável uso de antitreponemicos pelos doentes, uma vez que a terapeutica empírica pelo arsênico e mercúrio é muito espalhada na Amazônia. Histopatológicamente, encontraram na “lesão recente”: hiperqueratose, hiperacantose, exocitose, exoserose e espongiose na epiderme; e infiltração de células redondas, edema e diltação dos capilares no derma papilar e subpapilar; pela impregnação, acharam irregularidade na distribuição do pigmento melanico, assim como melanóforos entre as células inflamatórias do derma. Na “lesão tardia” observaram: notável atrofia do epiderme, reduzida às vezes , a 3 a 5 camadas celulares, havendo desaparecimento das papilas dérmicas; no derma, havia discreta infiltração de células redondas, relacionadas aos vasos sanguineos, ao lado de macrófagos melaniferos mais ou menos abundantes; pela impregnação, quanto às alterações pigmentares, foram observadas todas as graduações, desde a completa ausência de pigmento na basal, até um acúmulo notável de melanina, atingindo as próprias células de Malpighi. 7) Com o tratamento pelo “neo-salvarsan” os AA observaram grandes melhoras e mesmo cura aparente, com 6 a 8 injeções. Certas manifestações acromicas vitiligoides, antigas, não mostraram modificações apreciáveis com a terapêutica. 8) No Brasil, fora da Amazônia, tem sido descrito casos isolados de purú-purú, porém, na opinião dos autores, todos ou quase todos, são provavelmente, manifestações discromicas tardias de sífilis ou bouba, semelhantes aos publicados por um deles (F. N. G). Pensam do mesmo modo, quanto aos casos de pinta descritos fora da América: África, Egito, Argeria, Sahara, Trípoli, Turquestão, Filipinas, Iraque, Índia, Ceilão, etc. Ainda nesta mesma ordem de idéas, os autores negam validade ao conceito epidemiológico da existência de “casos isolados”, a não ser procedentes das “zonas pintogenas”. 9) Um dos autores (F. N. G.) emite a seguinte hipótese, que considera sugestiva, embora dificilmente demonstrável: Os treis treponemas (T. pallidum, T. pertenue e T. carateum), oriundos de um ancestral comum. tornaram-se peculiares respectivamente ao branco, ao preto e ao índio, mantendo-se assim isolados. Secundariamente, com as correntes migratórias, misturaram-se as doenças...

From allergy to schistosomes: role of Fc receptors and adhesion molecules in eosinophil effector function

The dual function of eosinophils has been evidenced in protective immunity against parasites as well as in pathological manifestations during allergic disorders. We have demonstrated that a new class of IgE receptors, FcepsilonRII/CD23, was involved in the functional duality of eosinophils and other proinflammatory cells. More recently, we have shown that FcepsilonRI, the high affinity IgE receptor thought to be only expressed by basophils and mast cells, was involved in eosinophil-mediated cytotoxicity against schistosomes as well as in mediator release. These results favour the view that both IgE and its receptors have been primarily associated to a protective immune response, rather than to pathology. Not only IgE receptors but also members belonging to the family of adhesion molecules can participate as co-receptors in eosinophil effector function. The inhibitory role of monoclonal antibodies to LewisX (LeX, CD15) or to selectins in eosinophil-mediated cytotoxicity towards schistosomes and the detection of LeX and 'selectin-like' molecules on schistosomula surface indicate a double interaction mediated by selectins and their carbohydrate ligands between eosinophils and schistosomula. These results suggest new functions for these adhesion molecules, previously known to be involved mainly in cell infiltration.

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.

The Evolution of Trypanosomes Infecting Humans and Primates

Based on phylogenetic analysis of 18S rRNA sequences and clade taxon composition, this paper adopts a biogeographical approach to understanding the evolutionary relationships of the human and primate infective trypanosomes, Trypanosoma cruzi, T. brucei, T. rangeli and T. cyclops. Results indicate that these parasites have divergent origins and fundamentally different patterns of evolution. T. cruzi is placed in a clade with T. rangeli and trypanosomes specific to bats and a kangaroo. The predominantly South American and Australian origins of parasites within this clade suggest an ancient southern super-continent origin for ancestral T. cruzi, possibly in marsupials. T. brucei clusters exclusively with mammalian, salivarian trypanosomes of African origin, suggesting an evolutionary history confined to Africa, while T. cyclops, from an Asian primate appears to have evolved separately and is placed in a clade with T. (Megatrypanum) species. Relating clade taxon composition to palaeogeographic evidence, the divergence of T. brucei and T. cruzi can be dated to the mid-Cretaceous, around 100 million years before present, following the separation of Africa, South America and Euramerica. Such an estimate of divergence time is considerably more recent than those of most previous studies based on molecular clock methods. Perhaps significantly, Salivarian trypanosomes appear, from these data, to be evolving several times faster than Schizotrypanum species, a factor which may have contributed to previous anomalous estimates of divergence times.

Programmed Cell Death in Procyclic Form Trypanosoma brucei rhodesiense - Identification of Differentially Expressed Genes during Con A Induced Death

Trypanosoma brucei rhodesiense can be induced to undergo apoptosis after stimulation with Con A. As cell death in these parasites is associated with de novo gene expression we have applied a differential display technique, Randomly Amplified Differential Expressed Sequence-Polymerase Chain Reaction (RADES-PCR) to the study of gene expression during Con A induced cell death in these organisms. Twenty-two differentially displayed products have been cloned and sequenced. These represent the first endogenous genes to be identified as implicated in cellular death in trypanosomatids (the most primitive eukaryote in which apoptosis has been described). Evidence for an ancestral death machinery, `proto-apoptosis' in single celled organisms is discussed.

Analysis of genetic diversity of Trypanosoma cruzi: an application of riboprinting and gradient gel electrophoresis methods

Analysis of restriction fragment length polymorphism (RFLP) profiles derived from digestion of polymerase chain reaction (PCR) products of the ribosomal 18S from Trypanosoma cruzi yields a typical `riboprint' profile that can vary intraspecifically. A selection of 21 stocks of T. cruzi and three outgroup taxa: T. rangeli, T. conorhini and Leishmania braziliensis were analysed by riboprinting to assess divergence within and between taxa. T. rangeli, T. conorhini and L. braziliensis could be easily differentiated from each other and from T. cruzi. Phenetic analysis of PCR-RFLP profiles indicated that, with one or two exceptions, stocks of T. cruzi could be broadly partitioned into two groups that formally corresponded to T. cruzi I and T. cruzi II respectively. To test if ribosomal 18S sequences were homogeneous within each taxon, gradient gel electrophoresis methods were employed utilising either chemical or temperature gradients. Upon interpretation of the melting profiles of riboprints and a section of the 18S independently amplified by PCR, there would appear to be at least two divergent 18S types present within T. cruzi. Heterogeneity within copies of the ribosomal 18S within a single genome has therefore been demonstrated and interestingly, this dimorphic arrangement was also present in the outgroup taxa. Presumably the ancestral duplicative event that led to the divergent 18S types preceded that of speciation within this group. These divergent 18S paralogues may have, or had, different functional pressures or rates of molecular evolution. Whether or not these divergent types are equally transcriptionally active throughout the life cycle, remain to be assessed.

The ecotopes and evolution of triatomine bugs (triatominae) and their associated trypanosomes

Triatomine bug species such as Microtriatoma trinidadensis, Eratyrus mucronatus, Belminus herreri, Panstrongylus lignarius, and Triatoma tibiamaculata are exquisitely adapted to specialist niches. This suggests a long evolutionary history, as well as the recent dramatic spread a few eclectic, domiciliated triatomine species. Virtually all species of the genus Rhodnius are primarily associated with palms. The genus Panstrongylus is predominantly associated with burrows and tree cavities and the genus Triatoma with terrestrial rocky habitats or rodent burrows. Two major sub-divisions have been defined within the species Trypanosoma cruzi, as T. cruzi 1 (Z1) and T. cruzi 2 (Z2). The affinities of a third group (Z3) are uncertain. Host and habitat associations lead us to propose that T. cruzi 1 (Z1) has evolved in an arboreal, palm tree habitat with the triatomine tribe Rhodniini, in association with the opossum Didelphis. Similarly we propose that T. cruzi (Z2) and Z3 evolved in a terrestrial habitat in burrows and in rocky locations with the triatomine tribe Triatomini, in association with edentates, and/or possibly ground dwelling marsupials. Both sub-divisions of T. cruzi may have been contemporary in South America up to 65 million years ago. Alternatively, T. cruzi 2 (Z2) may have evolved more recently from T. cruzi 1 (Z1) by host transfers into rodents, edentates, and primates. We have constructed a molecular phylogeny of haematophagous vectors, including triatomine bugs, which suggests that faecal transmission of trypanosomes may be the ancestral route. A molecular clock phylogeny suggests that Rhodnius and Triatoma diverged before the arrival, about 40 million years ago, of bats and rodents into South America.

Evolution of ascariasis in humans and pigs: a multi-disciplinary approach

The nematode parasite Ascaris lumbricoides infects the digestive tracts of over 1.4 billion people worldwide, and its sister species, Ascaris suum, has infected a countless number of domesticated and feral pigs. It is generally thought that the putative ancestor to these worms infected either humans or pigs, but with the advent of domestication, they had ample opportunity to jump to a new host and subsequently specialize and evolve into a new species. While nuclear DNA markers decisively separate the two populations, mitochondrial sequences reveal that three major haplotypes are found in A. suum and in A. lumbricoides, indicating either occasional hybridization, causing introgression of gene trees, or retention of polymorphism dating back to the original ancestral species. This article provides an illustration of the combined contribution of parasitology, archaeoparasitology, genetics and paleogenetics to the history of ascariasis. We specifically investigate the molecular history of ascariasis in humans by sequencing DNA from the eggs of Ascaris found among ancient archeological remains. The findings of this paleogenetic survey will explain whether the three mitochondrial haplotypes result from recent hybridization and introgression, due to intensive human-pig interaction, or whether their co-occurrence predates pig husbandry, perhaps dating back to the common ancestor. We hope to show how human-pig interaction has shaped the recent evolutionary history of this disease, perhaps revealing the identity of the ancestral host.

Differential expression of notch signaling-related transcripts accompanies Pro-thymocyte proliferation and phenotype transition induced by epidermal growth factor plus insulin in fetal thymus organ cultures

Thymus regression upon stressing stimuli, such as infectious diseases, is followed by organ reconstitution, paralleling its development in ontogeny. A narrow window of thymus development was here studied, encompassing the pro-T lymphoid precursor expansion during specification stages, by the use of epidermal growth factor plus insulin (INS) in murine fetal thymus organ cultures. Aiming to disclose signaling pathways related to these stages, cultured thymus lobes had their RNA extracted, for the search of transcripts differentially expressed using RNAse protection assays and reverse transcriptase-polymerase chain reactions. We found no difference that could explain INS-driven thymocyte growth, in the pattern of transcripts for death/proliferation mediators, or for a series of growth factor receptors and transcriptional regulators known as essential for thymus development. Thymocyte suspensions from cultured lobes, stained for phenotype analysis by fluorescence activated cell sorting, showed a decreased staining for Notch1 protein at cell surfaces upon INS addition. We analyzed the expression of Notch-related elements, and observed the recruitment of a specific set of transcripts simultaneous and compatible with INS-driven thymocyte growth, namely, transcripts for Notch3, for its ligand Jagged2, and for Deltex1, a mediator of a poorly characterized alternative pathway downstream of the Notch receptor.

An overview of the effects of annexin 1 on cells involved in the inflammatory process

The concept of anti-inflammation is currently evolving with the definition of several endogenous inhibitory circuits that are important in the control of the host inflammatory response. Here we focus on one of these pathways, the annexin 1 (ANXA1) system. Originally identified as a 37 kDa glucocorticoid-inducible protein, ANXA1 has emerged over the last decade as an important endogenous modulator of inflammation. We review the pharmacological effects of ANXA1 on cell types involved in inflammation, from blood-borne leukocytes to resident cells. This review reveals that there is scope for more research, since most of the studies have so far focused on the effects of the protein and its peptido-mimetics on neutrophil recruitment and activation. However, many other cells central to inflammation, e.g. endothelial cells or mast cells, also express ANXA1: it is foreseen that a better definition of the role(s) of the endogenous protein in these cells will open the way to further pharmacological studies. We propose that a more systematic analysis of ANXA1 physio-pharmacology in cells involved in the host inflammatory reaction could aid in the design of novel anti-inflammatory therapeutics based on this endogenous mediator.

Mechanisms of eosinophil cytokine release

Human eosinophils have been demonstrated to contain a multitude of cytokines and chemokines that exist pre-formed within these cells. This content of pre-formed cytokines, with diverse potential biologic activities, provides eosinophils with capabilities distinct from most other leukocytes. The localization of pre-formed cytokines within eosinophils is both within specific granules and associated with substantial numbers of morphologically distinct cytoplasmic vesicles. Stimulation for release of specific cytokines, such as IL-4, leads to a regulated signal transduction cascade, which is dependent on the formation of leukotriene C4 within eosinophils where it acts as an intracrine mediator. IL-4 release occurs selectively and is by means of vesicular transport. The capabilities of eosinophils not only to rapidly release pre-formed cytokines but also to differentially regulate which cytokines are released endow eosinophils with distinct abilities in innate and acquired immunity.

P2X1 receptors and the endothelium

Adenosine triphosphate (ATP) is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation.

The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria

Malaria remains an important health problem in tropical countries like Brazil. Thrombocytopenia is the most common hematological disturbance seen in malarial infection. Oxidative stress (OS) has been implicated as a possible mediator of thrombocytopenia in patients with malaria. This study aimed to investigate the role of OS in the thrombocytopenia of Plasmodium vivax malaria through the measurement of oxidant and antioxidant biochemical markers in plasma and in isolated platelets. Eighty-six patients with P. vivax malaria were enrolled. Blood samples were analyzed for total antioxidant and oxidant status, albumin, total protein, uric acid, zinc, magnesium, bilirubin, total thiols, glutathione peroxidase (GPx), malondialdehyde (MDA), antibodies against mildly oxidized low-density lipoproteins (LDL-/nLDL ratio) and nitrite/nitrate levels in blood plasma and GPx and MDA in isolated platelets. Plasma MDA levels were higher in thrombocytopenic (TCP) (median 3.47; range 1.55-12.90 µmol/L) compared with the non-thrombocytopenic (NTCP) patients (median 2.57; range 1.95-8.60 µmol/L). Moreover, the LDL-/nLDL autoantibody ratio was lower in TCP (median 3.0; range 1.5-14.8) than in NTCP patients (median 4.0; range 1.9-35.5). Finally, GPx and MDA were higher in the platelets of TPC patients. These results suggest that oxidative damage of platelets might be important in the pathogenesis of thrombocytopenia found in P. vivax malaria as indicated by alterations of GPx and MDA.