Mesenchymal stem cell therapy for liver fibrosis

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

Detección de antígenos del virus del dengue en tejidos post mórtem / Detection of dengue virus antigen in post-mortem tissues

El panorama epidemiológico del dengue ha empeorado durante la última década. Las dificultades para prevenir su transmisión, así como la ausencia de una vacuna o tratamiento específico, lo convierten en un riesgo que desafía las medidas de salud pública y desborda la capacidad de los centros de salud y los sistemas de investigación a muchos niveles. Actualmente, la mayoría de los estudios sobre la patogenia de la infección centran su atención en la respuesta inmunitaria de las células T casi exclusivamente en infecciones secundarias y están dirigidos a identificar los mecanismos implicados en el desarrollo de la permeabilidad vascular y de los eventos hemorrágicos que lo acompañan. En este reporte se describe el caso de una menor de 45 días de edad con signos clínicos de dengue grave, cuyo diagnóstico se confirmó por reacción en cadena de la polimerasa de transcripción inversa en muestras de tejido post mórtem y por herramientas de apoyo diagnóstico de inmunohistoquímica, las cuales detectaron antígenos virales en todos los órganos obtenidos en la necropsia. Este caso subraya la importancia del estudio de las infecciones primarias asociadas a dengue grave, particularmente en niños, en quienes es más probable el desarrollo de la forma grave de la enfermedad sin una infección previa, y, además, pone de relieve la importancia de un diagnóstico que no se limite a las muestras de tejido hepático en el estudio de la patogenia de la infección viral.

The epidemiological situation of dengue has worsened over the last decade. The difficulties in preventing its transmission and the absence of a vaccine or specific treatment have made dengue a serious risk to public health, health centers and research systems at different levels. Currently, most studies on the pathogenesis of dengue infection focus on the T-cell immune response almost exclusively in secondary infections and are aimed at identifying the mechanisms involved in the development of vascular permeability and bleeding events that accompany the infection. This report describes the case of a baby girl less than 45 days of age with clinical signs of severe dengue, whose diagnosis was confirmed by reverse transcription polymerase chain reaction in post-mortem tissue samples and by the ancillary diagnostic use of immunohistochemistry, which detected viral antigens in all organs obtained at autopsy. This case highlights the importance of studying primary infections associated with severe dengue, particularly in children, who are more likely to develop the severe form of the disease without previous infection, and it further stresses the importance of a diagnosis that should not be based solely on the examination of liver tissue samples when studying the pathogenesis of the viral infection.

Ressignificação da vida do cuidador do paciente idoso com câncer / Ressignification of life of caregivers of elderly patients with cancer / Ressignificación de la vida de los cuidadores de pacientes de edad avanzada con cáncer

O estudo objetivou analisar o processo de tornar-se cuidador de idoso com câncer, submetido a quimioterapia, no contexto domiciliar. Estudo exploratório, com orientação teórico-metodológica da antropologia interpretativa e estudo de caso etnográfico. Os dados foram coletados de janeiro a setembro de 2009, com quatro cuidadores, por entrevistas semiestruturadas, observação e consulta em prontuários. Com a analise dos dados foram construídas quatro unidades de significação. Apresentamos neste artigo a unidade temática "A ressignificação da vida do cuidador", composta por aspectos positivos da atividade de cuidar e de ajudar a superar dificuldades, como união, solidariedade, oportunidade de reaproximação. As dificuldades foram mais evidentes, principalmente pelo despreparo para cuidar em domicilio, que levou a transformações nas relações familiares e sociais do cuidador, resultando em comprometimento dos aspectos físicos, emocionais e sociais. O enfermeiro, como agente do cuidar, deve prover qualificação adequada ao cuidador, auxiliando-o no enfrentamento da doença e na melhoria da relação cuidador-paciente-serviço.

The study aimed to analyze the process of becoming a caregiver of elderly patients with cancer, in chemotherapy, in the home context. This is an exploratory study with theoretical and methodological orientation of interpretative anthropology and ethnographic case study. Data were collected from January to September 2009, with four caregivers through semi-structured interviews, observation and consultation records. With data analysis were built four units of meaning. In this paper 'we are focusing the thematic unity "The ressignification of caregiver's life", composed by positive aspects of caregiving activities and of helping to overcome difficulties, such as union, solidarity, opportunity for reapproximation. The difficulties were more evident, especially being unprepared to care at home, which led to changes in the caregiver's familiar and social relationships, resulting in impairment of physical, emotional and social aspects. The nurse, as an agent of care, must provide adequate qualification to the caregivers, helping them in coping with the disease and improving the patient-caregiver-service relationship.

El estudio objetivó analizar el proceso de convertirse en cuidador de pacientes de edad avanzada con cáncer, que reciben quimioterapia, en el contexto del hogar. Estudio exploratorio, con orientación teórica y metodológica de la antropología interpretativa y del estudio de caso etnográfico. Los datos fueron recogidos entre enero y septiembre de 2009, con cuatro cuidadores, por medio de entrevistas semi-estructuradas, observación y consulta a los prontuarios. Con el análisis de los datos se construyeron cuatro unidades de significado. Aquí está presentada la unidad temática “La ressignificación de la vida de los cuidadores”, consistiendo de los aspectos positivos de las actividades de cuidar y de ayudar a superar dificultades como la unión, la solidaridad, la oportunidad de acercamiento. Las dificultades eran evidentes, sobre todo para los cuidadores no preparados para el cuidado en el hogar, lo que llevó a los cambios en las relaciones familiares y sociales del cuidador, resultando en el deterioro de los aspectos físicos, emocionales y sociales. La enfermera, como un agente de la atención, debe proporcionar la cualificación adecuada al cuidador, ayudando-o a hacer frente a la enfermedad y a mejorar la relación paciente-servicio-cuidador.

Control of Mycobacterium fortuitum and Mycobacterium intracellulare infections with respect to distinct granuloma formations in livers of BALB/c mice

Mycobacterium fortuitum is a rapidly growing nontuberculous Mycobacterium that can cause a range of diseases in humans. Complications from M. fortuitum infection have been associated with numerous surgical procedures. A protective immune response against pathogenic mycobacterial infections is dependent on the granuloma formation. Within the granuloma, the macrophage effector response can inhibit bacterial replication and mediate the intracellular killing of bacteria. The granulomatous responses of BALB/c mice to rapidly and slowly growing mycobacteria were assessed in vivo and the bacterial loads in spleens and livers from M. fortuitum and Mycobacterium intracellulare-infected mice, as well as the number and size of granulomas in liver sections, were quantified. Bacterial loads were found to be approximately two times lower in M. fortuitum-infected mice than in M. intracellulare-infected mice and M. fortuitum-infected mice presented fewer granulomas compared to M. intracellulare-infected mice. These granulomas were characterized by the presence of Mac-1+ and CD4+ cells. Additionally, IFN-γmRNA expression was higher in the livers of M. fortuitum-infected mice than in those of M. intracellulare-infected mice. These data clearly show that mice are more capable of controlling an infection with M. fortuitum than M. intracellulare. This capacity is likely related to distinct granuloma formations in mice infected with M. fortuitum but not with M. intracellulare.

Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14) was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN). The goats used consisted of group 1 (unimmunized and uninfected), group 2 [infected control - immunized with Quillaia A (Quil A)] and group 3 (immunized with rSm14 in Quil A and infected), each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6 percent (p < 0.001) and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05). This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

El hígado como órgano inmunológico / The liver and immune organ

La prevalencia de enfermedades hepáticas a nivel mundial registra cifras alarmantes. Solo la infección por malaria afecta a 500 millones de personas por año a nivel mundial. Enfermedades de etiología viral como hepatitis B y C, contribuyen al aumento de la casuística y por su caracter de patologías de tipo crónico evolucionan a formas severas como la fibrosis o los procesos neoplásicos. La relevancia del hígado como órgano central en la maquinaria metabólica del organismo y como clave partícipe de la respuesta inflamatoria sistémica, indican la necesidad de preservar sus capacidades funcionales.

Estudo de prevalência de auto-anticorpos não órgão específicos em população rural do nordeste brasileiro (Cavunge-Ba) / Study of the prevalence of autoantibodies not specific national rural population of Northeast Brazil (Cavunge-Ba)

Os auto-anticorpos hepáticos (AAH), incluindo os anticorpos antinúcleo (ANA), antimúsculo liso (SMA), antimicrossoma de fígado e rim do tipo 1 (anti-M1), anticitosol hepático do tipo 1 (anti-LC1) e antimitocôndria (AMA), podem ser encontrados em 1 por cento a 43 por cento dos indivíduos saudáveis, sendo considerados auto-anticorpos naturais. Por outro lado, são também considerados marcadores de enfermidades auto-imunes, particularmente hepatite auto-imune (HAI) e cirrose biliar primária (CBP), duas doenças auto-imunes do fígado de prevalência ainda desconhecida na população brasileira. Com o intuito de avaliar a freqüência de AAH na população normal e sua correlação com estado de doença e de investigar a prevalência de HAI e CBP no Brasil, foram coletadas amostras de soro de 725 indivíduos, aleatoriamente selecionados, residentes no povoado de Cavunge para realização de AAH por imunofluorescência indireta (IFI), empregando cortes de roedores, fibroblastos e células Hep-2. Os resultados foram comparados com dados demográficos e marcadores sorológicos de infecção por vírus A, B e C. Positividade para AAH foi considerada na presença de titulação igualou superior a 1:40, sendo considerada clinicamente relevante titulação igualou superior a 1:80. Cento e um indivíduos (14 por cento) apresentaram reatividade para AAH, a maioria com títulos de 1:40, sendo observada positividade para SMA, ANA e AMA em respectivamente 10 por cento, 4 por cento e 0,1 por cento dos indivíduos. Não foi encontrada reatividade para anti-LKM 1 e anti-LC 1. Os principais padrões de IFI para SMA e ANA foram, respectivamente, vaso e glomérulo I e nuclear pontilhado grosso. Apenas um indivíduo com SMA exibiu reatividade para anti-microfilamento em baixo título, não sendo observado...

HBeAg/anti-HBe, alanine aminotransferase and HBV DNA levels in HBsAg positive chronic carriers.

Serum samples from a total of 72 chronic hepatitis B virus carriers were analysed by serological, biochemical and molecular assays. The aim was to evaluate the relationship of the serological and biochemical parameters with molecular markers in order to assess the infectivity of virus. Out of 72 chronic HBsAg positive carriers, 28 patients were HBeAg positive and anti-HBe negative, 38 patients were HBeAg negative and anti-HBe positive, only 3 patients were positive for both HBeAg and anti-HBe and the rest 3 patients were negative for both markers. Detectable HBV DNA lcvcl was found in 92.86% HBsAg-positive/anti-HBe negative patients along with raised alanine aminotransferase (ALT) level (67.86%) compared with HBeAg-negative/anti-HBe positive carriers (36.84%) (p value = 0.02) and out a total of 38 HBeAg-negative/anti-HBe positive carriers, 12 (31.58%) patients had detectable lcvel of HBV DNA. Among the 14 HBeAg-negative/anti-HBe positive patients with elevated ALT level, 8 (57.14%) had detectable HBV DNA whereas out of 24 HBeAg-negative/anti-HBe positive patients with normal ALT level only 4 (16.66%) had detectablc HBV DNA lcvel. Significantly high rate of detection of HBV DNA was seen among anti-HBe positive patients with raised ALT level compared with the patients with normal ALT level (p value = 0.01).

Distribution of mast cells in relation to Schistosoma japonicum induced lesions in pigs.

The pathogenesis of schistosomiasis japonica has been extensively studied, however only little attention has been paid to the presence and localization of mast cells in relation to Schistosoma japonicum induced lesions. The aim of the present pilot study was to assess the parasitological and pathological responses in S. japonicum infected pigs with emphasis on the description of the distribution of mast cells in relation to lesions in the liver and cecum. Six pigs were exposed to 2,000 cercariae and examined 9 weeks post-infection. Three unexposed pigs of the same age served as helminth free controls. All infected pigs developed granulomatous hepatitis and typhlitis. In the liver, the degree of mast cell infiltration was higher in the infected pigs compared to the unexposed control group. This distinction could not be shown in the cecum. In both the liver and cecum, a mild to moderate number of mast cells were present within the granulomas. A significant relation was found between infection with S. japonicum and the mast cell infiltration in the liver. Due to their possible association with hepatic fibrosis, it seems as if they have some function in the fibrogenic process and thereby play a dual role in the pathogenesis of S. japonicum. In conclusion, the results show that mast cells are recruited to egg induced lesions in both the liver and the cecum.

Studies in a co-infection murine model of Plasmodium chabaudi chabaudi and Leishmania infantum: interferon-gamma and interleukin-4 mRNA expression

This work aimed to study the T helper type 1/2 (Th1/Th2) cytokine profile in a co-infection murine model of Plasmodium chabaudi chabaudi and Leishmania infantum. Expression of interferon-gamma and interleukin-4 (IL-4) was analyzed, in spleen and liver of C57BL/6 mice, by reverse transcriptase-polymerase chain reaction. High levels of IFN-gamma expression did not prevent the progression of Leishmania in co-infected mice and Leishmania infection did not interfere with the Th1/Th2 switch necessary for Plasmodium control. The presence of IL-4 at day 28 in co-infected mice, essential for Plasmodium elimination, was probably a key factor on the exacerbation of the Leishmania infection.

Serological diagnosis of autoimmune hepatobiliary diseases

Autoimmune hepatobiliary diseases AIHBD comprise autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and the overlap syndromes. Early diagnosis and treatment of AIHBD are essential for the prevention of the high morbidity, and mortality, that is, otherwise, associated with untreated patients. Screening for AIHBD relies heavily on the use of serological tests for the detection of serum autoantibodies that associate with the diseases. Understanding these tests, and the results produced, is important for the efficient diagnosis/exclusion of these diseases. In this review, we discuss the various tests available in the clinical immunology laboratory for screening of AIHBD and comment on the significance of the results produced by each test. We hope that this review will highlight this group of autoimmune diseases and lead to more efficient and earlier diagnosis, and treatment, of patients with AIHBD

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.

Alfa-1 Antitrispsina e esquistossomose mansônica: estudo imunohistoquimico do fígado em portadores da forma hepatoesplênica / Alfa-1 Antitrypsin and mansoni schistomiasis: Immunohistochemical study of liver in the hepatosplenic form carriers

A alfa 1- antitripsina (alfa 1- AT), glicoproteína sintetizada no fígado, tem potente ação inibitória de proteases, principalmente de elastase leucocitária. A deficiência de alfa 1 - AT geneticamente determinada, caracteriza-se por baixos níveis plasmáticos e está associada `a predisposição para doença pulmonar crônica degenerativa e cirrose hepática. Polímeros mutantes da alfa 1 -AT acumulam-se no citoplasma dos hepatócitos periportais, em geral sob forma de glóbulos identificáveis por imunohistoquímica. Para avaliar a ocorrência desses depósitos na forma hepatoesplênica (FHE) da esquistossomose mansônica, fragmentos de trinta indivíduos foram estudados pela técnica da peroxidase anti-peroxidase, utilizando-se um anticorpo policlonal anti-alfa 1- AT. Como controle, foram examinados fragmentos hepáticos de oito indivíduos sem hepatopatia originários de área não endêmica. A reação foi negativa no grupo controle. Em todos os esquistossomóticos, observou-se marcação positiva para alfa 1-AT, predominante em hepatócitos periportais, e com padrão finamente granular e difuso. Em apenas um caso encontraram-se depósitos globulares típicos, também visualizados pelas técnicas histólogicas de rotina. Embora se acredite que a deficiência genética de alfa 1- AT não desempenhe um papel significativo na patogênese da FHE, é possível que o padrão imunohistoquímico observado neste estudo esteja de alguma forma relacionado aos mecanismos fibrogênicos portais da FHE da esquistossomose mansônica

Detection of immunoglobulin G in the lung and liver of hamsters with visceral leishmaniasis

Several organs are affected in visceral leishmaniasis, not only those rich in mononuclear phagocytes. Hypergammaglobulinemia occurs during visceral leishmaniasis; anti-Leishmania antibodies are not primarily important for protection but might be involved in the pathogenesis of tissue lesions. The glomerulonephritis occurring in visceral leishmaniasis has been attributed to immune complex deposition but in other organs the mechanism has not been studied. In the current study we demonstrated the presence of IgG in the lung and liver of hamsters with visceral leishmaniasis. Hamsters were injected intraperitoneally with 2 x 10(7) amastigotes of Leishmania (Leishmania) chagasi and the presence of IgG in the liver and lung was evaluated at 7, 15, 30, 45, 80 and 102 days postinfection (PI) by immunohistochemistry. The parasite burden in the spleen and liver increased progressively during infection. We observed a deposit of IgG from day 7 PI that increased progressively until it reached highest intensity around 30 and 45 days PI, declining at later times. The IgG deposits outlined the sinusoids. In the lung a deposit of IgG was observed in the capillary walls that was moderate at day 7 PI, but the intensity increased remarkably at day 30 PI and declined at later times of infection. No significant C3 deposits were observed in the lung or in the liver. We conclude that IgG may participate in the pathogenesis of the inflammatory process of the lung and liver occurring in experimental visceral leishmaniasis and we discuss an alternative mechanism other than immune complex deposition

A single strain of Mycobacterium bovis bacillus Calmette-Guérin (BCG) grown in two different media evokes distinct humoral immune responses in mice

Two attenuated bacillus Calmette-Guérin (BCG) preparations derived from the same Moreau strain, Copenhagen but grown in Sauton medium containing starch and bacto-peptone (onco BCG, O-BCG), or asparagine (intradermal BCG, ID-BCG), exhibited indistinguishable DNA sequences and bacterial morphology. The number of viable bacilli recovered from spleen, liver and lungs was approximately the same in mice inoculated with the vaccines and was similarly reduced (over 90 percent) in mice previously immunized with either BCG vaccine. The humoral immune response evoked by the vaccines was, however, distinct. Spleen cell proliferation accompanying the growth of bacilli in tissue was significantly higher in mice inoculated with O-BCG. These cells proliferated in vitro upon challenge with the corresponding BCG extract. Previous cell treatment with mAb anti-CD4 T cells abolished this effect. Anti-BCG antibodies, as assayed either in serum by ELISA or by determining the number of antibody-producing spleen cells by the spot-ELISA method, were significantly higher in mice inoculated with ID-BCG. Anti-BCG antibodies were detected in all immunoglobulin classes, but they were more prevalent in IgG with the following distribution among its isotypes: IgG1>(IgG2a = IgG2b)>IgG3. When some well-characterized Mycobacterium tuberculosis antigens were used as substitutes for BCG extracts in ELISA, although antibodies against the 65-kDa and 96-kDa proteins were detected significantly, antibodies against the 71-kDa, 38-kDa proteins and lipoarabinomannan were only barely detected or even absent. These results indicate that BCG bacilli cultured in Sauton-asparagine medium permitted the multiplication of bacilli, tending to induce a stronger humoral immune response as compared with bacilli grown in Sauton-starch/bacto-peptone-enriched medium

Tumour necrosis factor-alpha and interleukin-2 in pus aspirate and blood in patients with amoebic liver abscess.

OBJECTIVES: Cell mediated immunity (CMI), cytokines and humoral immunity have been implicated in the pathogenesis of invasive amoebiasis. METHODS: The role of cytokines--tumour necrosis factor-alpha (TNF-alpha) and interleukin 2 (IL-2) in blood and pus aspirate was studied in 20 patients of amoebic liver abscess (ALA), before and after treatment and 10 controls. RESULTS: The mean TNF-alpha levels (pg/ml) in the controls and before treatment in the patients in serum and pus were 24.3 +/- 11.6, 28 +/- 14.5 and 161.2 +/- 81.3 (p < 0.002) respectively. The mean IL-2 levels (pg/ml) in the controls, serum and pus aspirate in the patients prior to treatment were 10.3 +/- 8.5, 39.2 +/- 26.1 and 117.0 +/- 65.9 respectively. The levels in the patients after therapy, increased to 47 +/- 25.7 (p < 0.001) and 134 +/- 59.4 (p < 0.01). CONCLUSIONS: The higher levels of TNF-alpha and IL-2 in the pus aspirate compared to blood pre treatment, supports the role of locally released cytokines in the target organ i.e. liver in amoebiasis. The rise in values observed after therapy are indicative of increased macrophage activity due to CMI occurring late in the course of the disease which may contribute to disease limitation and localisation in amoebiasis. The study suggests that locally released cytokines play an important role in the pathogenesis of ALA.

Immunohistopathological reactions for liver-specific membrane lipo-protein in experimental autoimmune hepatitis.

Antibody to the hepatocyte membrane protein, was induced in inbred strain C57BL/6 and C3H mice by immunisation with 100,000 g supernatant of syngeneic liver homogenate in CFA. Three weekly intraperitoneal injection of 200 ul of liver homogenate with CFA for continuous 4 weeks gave the best possible result. Histopathological changes were characterised mainly by perivascular inflammatory infiltrates and hepatocyte necrosis which mimicked human autoimmune hepatitis. In one of the immunological parameters, antibody to hepatocyte membrane protein (LSP) has been demonstrate by ouchterlony method in the test serum of those animals, who had received weekly doses of liver antigen. Thus in experimental autoimmune liver disease, semi-purified syngeneic liver fluid (S-100) leads to hepatic destruction and to an inflammatory process with several features in common with human chronic aggressive hepatitis. The presence of antibody against syngeneic liver antigen (S-100) in the test sera emphasizes that hepatocyte membrane protein does have an important role in liver tissue pathogenesis and disease process in experimental model. In this study we tried to prove that hepatocyte membrane protein may act as a target antigen in developing experimental autoimmune hepatitis.

Circulating immune complex in murine autoimmune hepatitis.

High level of circulating immune complexes (CIC) in the serum has been reported in different forms of hepatitis particularly in complicated cases of viral hepatitis due to hepatitis B virus (HBV) infection. In this study CIC level in experimental autoimmune hepatitis were assessed by detection of polyethylene glycol (PEG) index. The sera of mice with established autoimmune hepatitis (EAH) confirmed by histopathological study showed higher PEG index (C57BL/6 mice: 34.56 +/- 6.28 and C3H mice: 31.95 +/- 28.99). The control healthy mice showed lower PEG index (C57BL/6 mice: 19.48 +/- 6.85 and C3H mice: 21.27 +/- 6.1). The high level of PEG index in EAH was found statistically significant. The role of CIC in the development of autoimmune hepatitis is discussed.

Significado clínico de los marcadores serológicos de las hepatitis virales / Clinical significance of viral hepatitis serologic markers

Las hepatitis virales son aquellas enfermedades infecciosas que tienen afinidad por el tejido hepático, al cual lesionan de manera selectiva. En el momento actual existen alrededor de 26 virus que pueden producir la enfermedad; sin embargo, sólo 6 están bien definidos desde el punto de vista biológico y son conocidos con las letras del alfabeto: A, B, C, D, E y G. Como cada uno de ellos tiene evolución diferente es necesario conocer con precisión la etiología de la hepatitis para saber el pronóstico del paciente y efectuar un tratamiento adecuado. Afortunadamente cada uno de ellos tiene antígenos y anticuerpos que se pueden determinar. En el presente informe se revisan el momento en que están presentes los antígenos y los anticuerpos de los principales virus que producen hepatitis, las técnicas de laboratorio que se utilizan, la duración de presentación y lo que significa desde el punto de vista clínico su presencia

Glycosphingolipid antigens from Leishmania (L.) amazonensis amastigotes. Binding of antiglycosphingolipid monoclonal antibodies in vitro and in vivo

Specific glycosphingolipid antigens of Leishmania (L.) amazonensis amastigotes reactive with the monoclonal antibodies (MoAbs) ST-3, ST-4 and ST-5 were isolated, and their structure was partially elucidated by negative ion fast atom bombardment mass spectrometry. The glycan moieties of five antigens presented linear sequences of hexoses and N-acetylhexosamines ranging from four to six sugar residues, and the ceramide moieties were found to be composed by a sphingosine d18:1 and fatty acids 24:1 or 16:0. Affinities of the three monoclonal antibodies to amastigote glycosphingolipid antigens were also analyzed by ELISA. MoAb ST-3 reacted equally well with all glycosphingolipid antigens tested, whereas ST-4 and ST-5 presented higher affinities to glycosphingolipids with longer carbohydrate chains, with five or more sugar units (slow migrating bands on HPTLC). Macrophages isolated from footpad lesions of BALB/c mice infected with Leishmania (L.) amazonensis were incubated with MoAb ST-3 and, by indirect immunofluorescence, labeling was only detected on the parasite, whereas no fluorescence was observed on the surface of the infected macrophages, indicating that these glycosphingolipid antigens are not acquired from the host cell but synthesized by the amastigote. Intravenous administration of 125I-labeled ST-3 antibody to infected BALB/c mice showed that MoAb ST-3 accumulated significantly in the footpad lesions in comparison to blood and other tissues.