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...

Os grandes clímaces do Brasil: II - considerações gerais sôbre a vegetação da região amazônica

Um eine neue phytogeographische Einteilung des Amazonasgebietes (Região Amazônica) in Angriff nehmen zu koennen, zieht der Autor anfangs die Ergebnisse der geomorphologischen, klimatologischen und floristischen Studien aelterer und neuerer Beobachter heran und setzt sie in Uebereinstimmung mit den oekologischen Resultaten. Die Einteilung umfasst: A. Region des guianensischen Schildes mit 5 Subregionen; B. Region der Sedimentboeden mit 3 teilweise unterteilten Subregionen; C. Region des nordbrasilianischen Schildes mit 2 unterteilten Subregionen. In den drei Gebieten finden wir, infolge der verschiedenen geologischen Verhaeltnisse, praktisch alle Vegetationstypen Brasiliens, obwohl das Klima uniform (warm-feucht) ist. Nach der Beurteilung der verschiedenen Theorien ueber die geologischen und floristischen Gegebenheiten und unter Hinzufuegung biologischer Tatsachen (Samenverbreitung) kommt der Autor zum Schluss, dass in dem Gebiet vier grosse, endemisch begruendete Baumzonen bestehen, deren Existenz auf dem heutigen hydrographischen Netz und seinen oekologischen Bedingugen beruht: 1. Die Trockengebiete der kristallinen Hochebenen am oberen Rio Negro und Rio Branco und auf dem suedamazonischen Schild; 2. Eine die Sedimentregion umgebende Zone; 3. Die Gebiete der Hochebenen und die hoeher gelegenen Teile der Sandaufschuettungen; 4. Die fruchtbaren Sedimentebenen. Ausserdem kann man die wechselnden Gebiete periodischer Ueberschwemmungen als kennzeichnende Zonen der augenblicklichen Entwicklungsphase des Amazonasbeckens ansehen.

Lymnaea viatrix and Lymnaea columella in the neotropical region: a distributional outline

A review of lymnaeid samples collected by the author from 106 localities in Mexico, Cuba, Jamaica, Haiti, Dominican Republic, Puerto Rico, Martinique, Saint Lucia, Guatemala, Costa Rica, Panamá, Ecuador, Peru, Bolivia, Chile, Argentina, Uruguay andBrazil showed that one of them (from Ecuador) belonged to Lymnaea cousini Jousseaume, 1887, and all the others to either L. viatrix Orbigny, 1835 or l. columella Say, 1817. The ranges of L. viatrix and L. columella overlap in Middle America, and in northern and southern South America (Venezuela-Colombia-Ecuador and northeastern Argentina-Uruguay-southernmost Brazil, respectively). L. viatrix was the only species found in Peru west of the Andes and in Chile, and is supposed to have migrated eastward to Argentina via the Negro river basin. The range of L. columella in South America is discontinuous. The species has been recorded from Venezuela, Colombia and Ecuador and, east of the Andes, from latitudes 15º S (central-west Brazil) to 35º S (La Plata, Argentina). Such a gap may be attributed to either introduction from the northern into the southern area, or migration along the unsampled region on the eastern side of the Andes, or extinction in the now vacant area. No lymnaeids have been found so far in Brazil north of latitude 15º S and in the Guianas.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study.

BACKGROUND & AIMS: Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy. METHODS: The analysis included 1362 individuals: 1015 with chronic hepatitis C and 347 who spontaneously cleared the virus (448 were coinfected with human immunodeficiency virus [HIV]). Responses to pegylated interferon alfa and ribavirin were assessed in 465 individuals. Associations between more than 500,000 single nucleotide polymorphisms (SNPs) and outcomes were assessed by multivariate logistic regression. RESULTS: Chronic hepatitis C was associated with SNPs in the IL28B locus, which encodes the antiviral cytokine interferon lambda. The rs8099917 minor allele was associated with progression to chronic HCV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.74-3.06; P = 6.07 x 10(-9)). The association was observed in HCV mono-infected (OR, 2.49; 95% CI, 1.64-3.79; P = 1.96 x 10(-5)) and HCV/HIV coinfected individuals (OR, 2.16; 95% CI, 1.47-3.18; P = 8.24 x 10(-5)). rs8099917 was also associated with failure to respond to therapy (OR, 5.19; 95% CI, 2.90-9.30; P = 3.11 x 10(-8)), with the strongest effects in patients with HCV genotype 1 or 4. This risk allele was identified in 24% of individuals with spontaneous HCV clearance, 32% of chronically infected patients who responded to therapy, and 58% who did not respond (P = 3.2 x 10(-10)). Resequencing of IL28B identified distinct haplotypes that were associated with the clinical phenotype. CONCLUSIONS: The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection.

Quoi de neuf pour le traitement de l'hépatite B [What's new in the treatment of hepatitis B infection?]

Although the number of available antiviral drugs for hepatitis B infection (VHB) today is higher than ever, treatment of chronic VHB infection is still often managed by specialists because of the complex natural history of this viral infection and of the risk of selecting viral strains that are resistant to therapy. Different clinical and virological aspects need to be considered to establish a correct indication for therapy. Once antiviral therapy has been started, patients need close monitoring to guarantee adequate compliance and to detect promptly the selection of viral variants resisting to therapy.

Diagnóstico de la cuenca de río Frío, Arenal - Huetar Norte, Costa Rica

El diagnóstico de la cuenca de río Frío forma parte del proyecto Araucaria XXI "Unidos por el agua", el objetivo principal de este estudio es conseguir una visión general en 4 ámbitos: biofísico, social, económico y administrativo para conocer el estado actual de la zona y poder conocer las principales problemáticas para posteriormente realizar el Plan de Manejo. La cuenca del río Frío se localiza en el Área de Conservación Huetar- Norte y esta constituida principalmente por los cantones de Guatuso y Los Chiles. Se trata de una zona con una importante variedad de ecosistemas y con una importante diversidad biológica, principalmente la avifauna. Esta zona ha sufrido a lo largo de los años una importante transformación paisajística, las grandes masas boscosas han sido modificadas muy rápidamente en pastos y cultivos, que son las principales actividades económicas. Se trata de una zona aislada de Costa Rica y fronteriza con Nicaragua, la situación de la zona tanto económica como social es mala, presenta índices de analfabetismo elevados, falta de fuentes de empleo, falta de recursos económicos y de presencia institucional. Las infraestructuras viales presentan un estado muy deteriorado que dificulta el desarrollo de actividades turísticas. A todo este conjunto de problemática observadas gracias al diagnóstico se les han planteado toda una serie de estrategias orientativas para mejorar la gestión de la cuenca del río Frío que buscan un desarrollo más sostenible de la zona.

Genotype 3 is associated with rapid histological progression in chronic HCV infection

While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of the present study was to assess independent predictors for fibrosis progression. Methods: We identified 1540 patients from the Swiss Hepatitis C Cohort database with at least one liver biopsy prior to antiviral treatment. Factors associated with fibrosis stage, steatosis and histological activity were assessed in univariate and multivariate regression models. Fibrosis progression rate per year was calculated in a subgroup of 1263 patients, in whom risk factors were assessed by cumulative incidence curves, logistic and linear regression models. Results: Independent risk factors for rapid fibrosis progression included male sex (OR = 1.66, 95% CI 1.25-2.21, P <0.001), age at infection (OR = 1.08, 95% CI 1.06-1.10, P <0.001), histological activity (OR = 2.14, 95% CI 1.61-2.85, P <0.001) and genotype 3 (OR = 1.97, 95% CI 1.43-2.72, P <0.001). Genotype 2 was associated with slow progression (OR = 0.51, 95% CI 0.30-0.89, P = 0.02), but this observation may be due to the decreased prevalence of genotype 2 over the last decades, leading to an overrepresentation of subjects with genotype 2 with a slow progression rate. Conclusion: This study shows a significant association of genotype 3 with accelerated fibrosis. While assessing risk factors for fibrosis progression, the changing epidemiology of HCV genotypes over time needs to be taken into account.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

IL28B polymorphism is significantly correlated with ifn anti-viral effectiveness already on first day of pegylated interferon-alpha and ribavirin therapy of chronic HCV infection

Background and Aims: Recently, single nucleotide polymorphisms (SNPs) in IL28B were shown to correlate with response to pegylated interferon-a (IFN) and ribavirin therapy of chronic HCV infection. However, the cause for the SNPs effect on therapy response and its application for direct anti-viral (DAV) treatment are not clear. Here, we analyze early HCV kinetics as function of IL28B SNPs to determine its specific effect on viral dynamics. Methods: IL28B SNPs rs8099917, rs12979860 and rs12980275 were genotyped in 252 chronically HCV infected Caucasian naïve patients (67% HCV genotype 1, 28% genotype 2-3) receiving peginterferonalfa- 2a (180 mg/qw) plus ribavirin (1000-1200 mg/qd) in the DITTO study. HCV-RNA was measured (LD = 50 IU/ml) frequently during first 28 days. Results: RVR was achieved in 33% of genotype 1 patients with genotype CC at rs12979860 versus 12-16% for genotypes TT and CT (P < 0.03). Significant (P < 0.001) difference in viral decline was observed already at day 1 (see Figure). First phase decline was significantly (P < 0.001) larger in patients with genotype CC (2.0 log) than for TT and CT genotypes (0.6 and 0.8), indicating IFN anti-viral effectiveness in blocking virion production of 99% versus 75-84%. There was no significant association between second phase slope and rs12979860 genotype in patients with a first phase decline larger than 1 log. HCV kinetics as function of IL28b SNP. The same trend (not shown) was observed for HCV genotype 2-3 patients with different SNP genotype distribution that may indicate differential selection pressure as function of HCV genotype. Similar results were observed for SNPs rs8099917 and rs12980275, with a strong linkage disequilibrium among the 3 loci allowing to define the composite haplotype best associated with IFN effectiveness. Conclusions: IFN effectiveness in blocking virion production/ release is strongly affected by IL28B SNPs, but not other viral dynamic properties such as infected cell loss rate. Thus, IFN based therapy, as standard-of-care or in combination with DAV, should consider IL28B SNPs for prediction and personalized treatment, while response to pure DAV treatment may be less affected by IL28B SNPs. Additional analyses are undergoing to pinpoint the SNP effect on IFN anti-viral effectiveness.

Interleukin-28B polymorphisms, IP-10, viral load and age predict the outcome of therapy in genotype 1 hepatitis C virus under real-life conditions

Background and Aims: IL28B polymorphisms, interferon (IFN)-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score have been reported to predict rapid (RVR) and sustained (SVR) virological response in chronic hepatitis C (CHC), but it is not known whether these factors represent independent, clinically useful predictors. The aim of the study was to assess factors (including IL28B polymorphisms, IP-10 levels and HOMA-IR score) independently predicting response to therapy in CHC under real life conditions.Methods: Multivariate analysis of factors predicting RVR and SVR in 280 consecutive, treatment-naive CHC patients treated with pegylated IFN alpha and ribavirin in a prospective multicenter study.Results: Independent predictors of RVR were HCV RNA < 400,000 IU/ml (OR11.37; 95% CI 3.03-42.6), rs12980275 AA (vs. AG/GG) (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR = 0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age < 40 yrs (OR = 4.79; 1.50-15.34) and HCV RNA < 400,000 IU/ml (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98-19.74) and age < 40 yrs (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (32 of 33, 97%; OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99; p=0.009) or 3 patients (OR 7.8, 1.43-42.67; p=0.01).Conclusions: In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pretreatment prediction of SVR. HOMA-IR score is not associated with viral response.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND: The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS: CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS: Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS: The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.