Few publications have compared ultrasound (US) to histology in diagnosing schistosomiasis-induced liver fibrosis (LF); none has used magnetic resonance (MR). The aim of this study was to evaluate schistosomal LF using these three methods. Fourteen patients with hepatosplenic schistosomiasis admitted to hospital for surgical treatment of variceal bleeding were investigated. They were submitted to upper digestive endoscopy, US, MR and wedge liver biopsy. The World Health Organization protocol for US in schistosomiasis was used. Hepatic fibrosis was classified as absent, slight, moderate or intense. Histology and MR confirmed Symmers' fibrosis in all cases. US failed to detect it in one patient. Moderate agreement was found comparing US to MR; poor agreement was found when US or MR were compared to histology. Re-classifying LF as only slight or intense created moderate agreement between imaging techniques and histology. Histomorphometry did not separate slight from intense LF. Two patients with advanced hepatosplenic schistosomiasis presented slight LF. Our data suggest that the presence of the characteristic periportal fibrosis, diagnosed by US, MR or histology, associated with a sign of portal hypertension, defines the severity of the disease. We conclude that imaging techniques are reliable to define the presence of LF but fail in grading its intensity.

Tuberculosis is the most prevalent infectious disease in the world. Granuloma formation and caseous necrosis are hallmarks of M. tuberculosis infection and they represent the protective and inflammatory reactions in the infected tissues. The molecular mechanisms that mediate granuloma necrosis are still not well understood. Objectives: To immunolocalize and correlate the amounts of CD68+ macrophages and CD8+ lymphocytes to caseous necrosis extension in granulomas of tuberculous pleurisy. Methods: The study is a retrospective analysis of 30 pleural biopsies with histopathological diagnosis of chronic granulomatous pleurisy with caseous necrosis. These biopsies were classified according to necrosis intensity as minimal (N1), moderate (N2) and intense (N3). The number of granulomas was also observed and categorized as G1 (1 to 4 granulomas per section), G2 (5 to 8 granulomas per section), and G3 (more than 8 granulomas per section). Results: The means of CD68+ cells counts per mm² in N1, N2 and N3 categories of necrosis were 1,287 ± 254, 1086 ±181 and 930 ± 115 respectively. The means for CD8+ cells were 483.7 ± 396, 366.3 ± 43 and 558 ± 53 cells per mm² in N1, N2 and N3 respectively. Conclusions: There were no significant statistical correlations between necrosis extension and cell counts. In analyzed biopsies, the number of CD68+ cells was significantly higher than the number of CD8+ cells.

La tuberculosis es una de las enfermedades más prevalentes en el mundo. La formación del granuloma junto con la necrosis caseosa son características propias de la infección por M. tuberculosis y representan reacciones inflamatorias y protectoras en los tejidos infectados. No se conocen bien los mecanismos moleculares que median la necrosis en el granuloma. Los objetivos fueron inmunolocalizar y correlacionar la cantidad de macrófagos CD68+ y linfocitos CD8+ con la extensión de la necrosis caseosa, en los granulomas de tuberculosis pleural. Análisis retrospectivo que incluyeron 30 biópsias con diagnóstico histopatológico de tuberculosis pleural granulomatosa crónica con necrosis caseosa. Estas biópsias fueron clasificadas según la intensidad de necrosis como mínima (N1), moderada (N2) e intensa (N3). También se determinó el número de granulomas, que fueron clasificados como G1 (1 a4 granulomas por sección), G2 (5 a 8 granulomas por sección), y G3 (más de 8 granulomas por sección). La cuantificación de células CD68+ por mm² en las categorías N1, N2 y N3 de necrosis fue de 1,287 ± 254; 1086 ±181 y 930 ± 115, respectivamente. La cuantificación de las células CD68+ fue de 483,7 ± 396; 366,3 ± 43 y 558 ± 53 células por mm² para N1, N2 y N3, respectivamente. No hubo correlación estadísticamente significativa entre la extensión de la necrosis y la cuantificación celular. El número de células CD68+ fue significativamente mayor que el número de células CD8+ en las biópsias analizadas.

There is evidence in both human and experimental infection caused by Mycobacterium tuberculosis, that immunologic factors influence susceptibility to infection and the progress of the disease. The present study aims to evaluate the role of IFN- g upon inflammatory granulomatous response against M. bovis. To pursue that, C57BL/6 mice lacking the genes for synthesis of IFN- g (IFN- g-/-) and their wild-type counterparts (IFN- g+/+) were intravenously inoculated with M. bovis. The ability of M. bovis to survive and replicate in the liver and lungs was evaluated by counting colony-forming unit (CFU). The histopathological features of granulomatous inflammatory response in the liver and lungs were analyzed during the infection by M. bovis. Granuloma parameters such as, size (sectional area), granuloma volume, volume density, and numerical density were calculated in each point of infection. Bacillary load was higher in both organs of the animals that were IFN- g-/- than in IFN- g+/+ mice. Granulomas were observed in the IFN- g-/- mice after 30 days of infection and were detected earlier in controls (15 days of infection). Hepatic granulomas persisted in the IFN- g-/- mice, but in the IFN- g+/+ mice control of the inflammation. In conclusion, IFN- g influenced the multiplication of M. bovis, as well as modulated the granulomatous inflammation

Existen evidencias, tanto en humanos como en modelos experimentales, que factores inmunológicos influencian. durante la infección causada por la Mycobacterium tuberculosis, tanto la infección como la progresión de la enfermedad. Este estudio se propone evaluar el papel de IFN-g en la respuesta inflamatoria granulomatosa contra M. bovis. Para ello, se inocularon ratones C57BL/6 knockout para IFN- g (IFN- g-/-) y los correspondientes salvajes (IFN- g+/+) con M. bovis. Evaluamos la capacidad de la M. bovis de sobrevivir y replicarse en el hígado y pulmones mediante la cuantificación de unidades formadoras de colonias (CPU). También analizamos los aspectos histopatológicos de la respuesta inflamatoria granulomatosa en el hígado y los pulmones durante la infección con M. bovis. Para cada punto de infección, se calcularon los parámetros del granuloma, tales como el tamaño (área de sección), el volumen del granuloma, la densidad de volumen y densidad numérica. La carga bacilar fue mayor en los dos órganos estudiados procedentes de los ratones IFN- g-/-. Los granulomas de los ratones controles se detectaron a los 15 días, mientras que los de los ratones IFN-g no se detectaron hasta los 30 días post infección. Los granulomas hepáticos persistieron en los ratones IFN- g-/-. Como conclusión es posible afirmar que el IFN- g influencia la multiplicación por M. bovis, así como también modula la inflamación granulomatosa

Weaning Swiss mice were percutaneously infected with 30 cercariae of Schistosoma mansoni and submitted to a shifting either from a deficient to a balanced diet or vice-versa, for 24 weeks. The nutritional status was weekly evaluated by measurements of growth curves and food intake. Hepatic fibrosis and periovular granulomas were studied by histological, morphometric and biochemical methods. All mice fed on a deficient diet failed to develop periportal "pipestem" fibrosis after chronic infection. An unexpected finding was the absence of pipestem fibrosis in mice on normal diet, probably related to the sample size. The lower values for nutritional parameters were mainly due to the deficient diet, rather than to infection. Liver/body weight ratio was higher in "early undernutrition" group, after shifting to the balanced diet. Volume density and numerical density of egg granulomas reached lowest values in undernourished animals. The amount of collagen was reduced in undernourished mice, attaining higher concentrations in well-fed controls and in "late undernutrition" (balanced diet shifted to a deficient one), where collagen deposition appeared increased in granulomas. That finding suggested interference with collagen degradation and resorption in "late" undernourished animals. Thus, host nutritional status plays a role in connective tissue changes of hepatic schistosomiasis in mice.

Some unfavourable effects of malnutrition of the host on Schistosoma mansoni worm biology and structure have been reported based upon brigthfield microscopy. This paper aims to study by morphometric techniques, some morphological parameters in male and female adult worms recovered from undernourished albino mice in comparison with parasites recovered from well-fed infected mice. Undernourished animals were fed a multideficient and essentially low protein diet (RBD diet) and compared to well-fed control mice fed with the commercial diet NUVILAB. Seventy-five days post-infection with 80 cercarie (BL strain) animals were sacrificed. All adult worms were fixed in 10% formalin and stained with carmine chloride. One hundred male and 60 female specimens from each group (undernourished and control) were examined using an image system analysis Leica Quantimet 500C and the Sigma Scan Measurement System. The following morphometrical parameters were studied: body length and width, oral and ventral suckers, number and area of testicular lobes, length and width of ovary and uterine egg. For statistical analysis, the Student's t test for unpaired samples was applied. Significant differences (p < 0.05) were detected in body length and width, in parameters of suckers, uterine egg width, ovary length and area of testicular lobes, with lower values for specimens from undernourished mice. The nutritional status of the host has negative influence on S. mansoni adult worms, probably through unavailability of essential nutrients to the parasites.

São descritos dois casos de Hanseníase combinados com granuloma elastolítico de células gigantes. Embora uma ocorrência concomitante não possa ser excluída, uma possível relação patogenética entre as duas condições é postulada. É possível que um mecanismo imunológico desempenhe um papel no processo elastolítico, que poderia também ser causado por dano actínico na pele alterada pela Hanseníase.

Two cases of leprosy combined with elastolytic giant cell granuloma are reported. Though a coincidental occurrence cannot be excluded, a possible pathogenetic relationship between the two conditions is postulated. It is possible that an immunological mechanism plays a role in the elastolytic process, which could also be caused by actinic damage in the skin altered by leprosy.

Severe destruction of intrinsic cardiac nerves has been reported in experimental acute Chagas myocarditis, followed by extensive regeneration during the chronic phase of the infection. To further study this subject, the sympathetic and para-sympathetic intracardiac nerves of mice infected with a virulent Trypanosoma cruzi strain were analyzed, during acute and chronic infection, by means of histological, histochemical, morphometric and electron microscopic techniques. No evidences of destructive changes were apparent. Histochemical demonstration for acetylcholinesterase and catecholamines did not reveal differences in the amount and distribution of intracardiac nerves, in mice with acute and chronic Chagas myocarditis or in non-infected controls. Mild, probably reversible ultrastructural neural changes were occasionally present, especially during acute myocarditis. Intrinsic nerves appeared as the least involved cardiac structure during the course of experimental Chagas disease in mice.

O grau e a morfologia da degradação do colágeno foram comparativamente analisados em ratos com fibrose hepática recente (tratamento de oito semanas com tetracloreto de carbono) e tardia (igual tratamento por 12 semanas), e acompanhados após a suspensão da administração da droga. O desaparecimento da fibrose (quando quantitativamente avaliada) foi gradual e semelhante para ambos os grupos. As modificações vistas à microscopia de luz e ao microscópio eletrônico foram também semelhantes. Estes resultados inesperadamente negativos diferem de outros modelos de fibrose hepática e sugerem que o grau de agressão ao parênquima hepático seja um fator limitante da degradação da fibrose que se segue à remoção do agente causal. Assim sendo, não apenas a idade da fibrose, mas o estado geral de alteração do órgão atingido influenciam a degradação e remoção do colágeno.

The rate and morphology of collagen degradation were comparatively analyzed in rats with "early" and "late" carbon tetrachloride-induced hepatic fibrosis, during three different periods after discontinuation of the drug. Treatment with CCl4 lasted for eight weeks for the group of early fibrosis and 12 weeks for the late fibrosis group. Fibrosis gradually disappeared, but when quantitative methods were applied, the amount of collagen degradation and removal in early and late fibrosis did not reach statistical significance. The light microscope and ultrastructural changes were also qualitatively similar in both cases. Probably some long-lasting effects to the liver, induced by the drug, prevented early hepatic fibrosis from undergoing the characteristic ultrastructural changes seen during "acute" collagen degradation, as compared to other experimental models of hepatic fibrosis, after the causal agent is totally removed. Present findings suggest that not only the age of fibrosis but also the overall damage inflicted to the organ are limiting factors in the process of collagen degradation and removal.

Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

Hepatic Schistosoma mansoni periovular granulomas undergo changes in size, cellular composition and appearance with time. This phenomenom, known as "immunological modulation", has been thought to reflect host immunological status. However, as modulation has not been observed outside the liver, participation of local factors, hitherto little considered, seems crucial. Components of the extracellular matrix of periovular granulomas of the mouse were particularly studied in three different organs (liver, lung and intestine) and during three periods of infection time (acute, intermediate and chronic) by means of histological, biochemical and imunofluorescence techniques, while quantitative data were evaluated by computerized morphometry, in order to investigate participation of local factors in granuloma modulation. Results confirmed modulation as a exclusively hepatic phenomenom, since pulmonary and intestinal granulomas, formed around mature eggs, did not change size and appearance with time. The matricial components which were investigated (Type I, III and IV collagens, fibronectin, laminin, proteoglycans and elastin) were found in all granulomas and in all organs examined. However, their presence was much more prominent in the liver. Elastin was only found in hepatic granulomas of chronic infection. The large amount of extracellular matrix components found in hepatic granulomas was the main change responsible for the morphological aspects of modulation. Therefore, the peculiar environment of the liver ultimately determines the changes identified in schistosomal granuloma as "modulation".

Com o objetivo de avaliar se a retirada de maior número de fragmentos pleurais em um único sítio (A), bem como se a biópsia em um segundo sítio (B) da sua superfície, através do mesmo orifício cutâneo, acrescenta em rendimento diagnóstico aos três fragmentos habitualmente retirados, conduzimos um estudo prospectivo no Hospital Octávio Mangabeira, envolvendo 115 pacientes com indicação de biópsia pleural. Os fragmentos pleurais foram colocados em três frascos distintos: FRA1-3 = 3 primeiros fragmentos, FRA4-8 = 5 fragmentos subseqüentes e FRB1-5 = 5 fragmentos em segundo sítio da superfície pleural. Era retirada a agulha até o subcutâneo, feitas inclinação lateral e reintrodução no espaço pleural. A análise dos fragmentos provindos do FRA1-3 evidenciou granuloma em 72/92 casos de tuberculose (78,3%) e no FRA4-8 e FRB1-5, em 74/92 casos (80,5%). Em 6/92 pacientes foram encontrados pleurite inespecífica no FRA1-3 e granuloma no FRA4-8, resultando em acréscimo diagnóstico de 8,3% (6 aos 72 pacientes). Em 7/92 pacientes (7,6%) a HP foi inespecífica no sítio A e mostrou granuloma no sítio B, resultando em acréscimo diagnóstico de 9,0% (7 aos 78 pacientes). A concordância histológica intra-observador teve um índice kappa de 0,62 (0,54 a 0,70) e interobservador de 0,64 (0,56 a 0,72). Concluímos que a realização de múltiplas biópsias em dois sítios diferentes da superfície pleural diagnosticou 13 pacientes que não obteriam diagnóstico definitivo se fossem retirados apenas três fragmentos pleurais, resultando em incremento diagnóstico de 18,0% (13 aos 72 diagnosticados no FRA1-3), sendo considerado significativo do ponto de vista médico e social.

For diagnostic purposes of pleural tuberculosis, three pleural fragments are routinely obtained from a single site by needle biopsy. The objective of this study is to compare the diagnostic yield of the routine procedure with two different approaches: harvesting five fragments on a single site (A), and collection of fragments at an additional site (B); from the same cutaneous orifice, the needle was partially removed up to the subcutaneous tissue and redirected at a 45º angle. The authors performed a prospective study in 115 patients submitted to pleural biopsy. The first three pleural fragments were placed in a vial (VA1-3), the 5 subsequent fragments obtained at the same site were placed in a second vial (VA4-8), and the five fragments from the second site were placed in a third vial (VB1-5). Analysis of fragments from VA1-3 revealed granuloma in 72/92 tuberculosis cases (78.3%), whereas in fragments VA5-8 and VB1-5, granuloma was observed in 74/92 cases (80.5%). In 6/92 patients the diagnosis at VA1-3 was non-specific pleuritis, but granuloma was found in VA4-8, resulting in a diagnosis increment of 8.3% (adding six to the 72 patients). In 7/92 patients (7.6%) the histopathological examination at site A led to a non-specific result but granuloma was found at site B, leading to a diagnostic increment of 9.0% (7 to 78 patients). Histological concordance of two examinations by the same pathologist had a kappa index of 0.62 (0.54 to 0.7) whereas concordance between two different pathologists had a kappa index of 0.64 (0.56 to 0.72). The performance of multiple biopsies at two different sites at the pleural surface led to an additional diagnosis of 13 patients, i.e., an increase of 18% (13 to 72) relative to the routine procedure. Considering the low cost increase of obtaining the fragments, adoption of this method is recommended in routine pleural tuberculosis diagnosis.

Histological, ultrastructural, morphometric and immunohistochemical data obtained from the study of spleens removed by splenectomy from 34 patients with advanced hepatosplenic schistosomiasis revealed that the main alterations were congestive dilatation of the venous sinuses and diffuse thickening of the splenic cords. Splenic cord thickening was due to an increase of its matrix components, especially type IV collagen and laminin, with the conspicuous absence of interstitial collagens, either of type I or type III. Deposition of interstitial collagens (types I and III) occurred in scattered, small focal areas of the red pulp, but in the outside of the walls of the venous sinuses, in lymph follicles, marginal zone, in the vicinity of fibrous trabeculae and in sidero-sclerotic nodules. However, fibrosis was not a prominent change in schistosomal splenomegaly and thus the designation "fibro-congestive splenomegaly" seems inadequate. Lymph follicles exhibited variable degrees of atrophy, hyperplasia and fibrous replacement, sometimes all of them seen in different follicles of the same spleen and even in the same examined section. Changes in white pulp did not seem to greatly contribute to increasing spleen size and weight, when compared to the much more significant red pulp enlargement.

Foram operadas cinqüenta ratas Wistar, adultas, separadas em seis grupos: 1, 2, 3, grupos isotado 1 e 2 e um grupo piloto. O lobo esquerdo da tireóide da rata foi dividido em três fragmentos similares e implantados no músculo esternoclidomastóideo, na raiz do mesentério e no ovário. Os tecidos implantados foram examinados histologicamente após dez, vinte e trinta dias. No grupo isolado I, depois de trinta dias a porção restante da tireóide in situ foi removida, passando a viver somente com os implantes. Para verificar aspectos funcionais, foram implantados três fragmentos da tireóide em um grupo isolado na raiz do mesentério. T3 T4 e TSH foram dosados no soro antes e após a retirada da tireóide. O exame histológico mostrou que o tecido tireóideo implantado sofria inicialmente discreta hipotrofia, retomando em seguida para os limites da normalidade. Os melhores resultados foram obtidos com o implante no mesentério. Os valores de T 3 e T 4 eram baixos e os de TSH altos. Apoiado nos resultados histológicos e hormonais, concluiu-se que no período estudado, a tireóide autotransplantada manteve sua arquitetura folicular, cumprindo a função de produzir os hormônios.

The left thyroid lobe of Wistar rats were separated into three fragments and implanted on the sternumcleidomastoid muscle, mesentery and right ovary. The implanted tissues were removed after 10, 20and 30 days and examined histologically. For each time period of transplantation ten rats were used. After 30 days the remaing thyroid tissue was removed. The animais subsequently lived with the transplants only. To verify implant function, three thyroid fragments were implanted on the mesentery in group one. The levels of T3 T4 and TSH were measured in serum before and after the surgery. Histologic examination showed mild atrophy in the beginning which subsequently returned to normality. The best results of transplantation were obtained with the implant on the mesentery. There were low T3 and T4 levels and high TSH levels. 1n conclusion, the autotransplanted thyroid gland sustained its folicular architecture and its endocrinological function, in the studied period.

Lesions involving the sympathetic (para-vertebral ganglia) and para-sympathetic ganglia of intestines (Auerbach plexus) and heart (right atrial ganglia) were comparatively analyzed in mice infected with either of three different strain types of Trypanosoma cruzi, during acute and chronic infection, in an attempt to understand the influence of parasite strain in causing autonomic nervous system pathology. Ganglionar involvement with neuronal destruction appeared related to inflammation, which most of the times extended from neighboring adipose and cardiac, smooth and striated muscular tissues. Intraganglionic parasitism was exceptional. Inflammation involving peripheral nervous tissue exhibited a focal character and its variability in the several groups examined appeared unpredictable. Although lesions were generally more severe with the Y strain, comparative qualitative study did not allow the conclusion, under the present experimental conditions, that one strain was more pathogenic to the autonomic nervous system than others. No special tropism of the parasites from any strain toward autonomic ganglia was disclosed.

Em camundongos submetidos à ligadura parcial da veia porta e infecção pelo Schistosoma mansoni, os granulomas periovulares apareceram em grande número nos pulmões, comprovando a validade do modelo de Warren. Histologicamente os granulomas eram representados por agregados celulares compactos no seio de escasso estroma. Os macrófagos (células epitelióides) e eosinófilos eram os elementos celulares predominantes, vindo em seguida os linfóticos e plasmócitos. Ultraestruturalmenle, as células do granuloma exibiam íntimo contacto de suas membranas, com varios pontos de adesão, mas sem formar estruturas juncionais mais específicas. Os granulomas formados em torno a ovos maduros tinham tamanho, forma e composição celular similares após 10, 18 ou 25 semanas de infecção. Este aspecto contrastava com o que aparecia nos granulomas hepáticos os quais exibiam a clássica modulação. Os granulomas que envolviam as paredes arteriolares exibiam proliferação muscular, endotelial, com formação de novas vias vasculares e fibrose. As diferenças morfológicas observadas nos granulomas formados em diferentes locais e órgãos apontam para a importância de se considerar fatores locais (estromais) no determinismo dos padrões das respostas inflamatórias.

Numerous pulmonary schistosome egg granulomas were present in mice submitted to partial portal vein ligation (Warren's model). The granulomas were characterized by cellular aggregations formed within alveolar tissue. Main cellular types were macrophages (epithelioid cells), eosinophils, plasma cells and lymphocytes. These cells were supported by scanty fibrous stroma and exhibited close membrane contact points amongst themselves, but without forming specialized adhesion apparatus. When granulomas involved arterial structures, proliferation of cndothelial and smooth muscle cells occurred and fibrosis associated with angiogenesis became more evident. Granulomas formed around mature eggs in the pulmonary alveolar tissue presented approximately the same size and morphology regardless of the time of infection, the latter being 10, 18 and 25 weeks after cercarial exposure. This persistence of morphological appearance suggests that pulmonary granulomas do not undergo immunological modulation, as is the case with the granulomas in the liver and, to a lesser extent, in the intestines. Probably, besides general immunological factors, local (stromal) factors play an important role in schistosomal granuloma modulation.