Pathogenesis of hepatic septal fibrosis associated with Capillaria hepatica infection of rats

Septal fibrosis is a common form of hepatic fibrosis, but its etiology and pathogenesis are poorly understood. Rats infected with the helminth Capillaria hepatica constitute a good experimental model of such fibrosis. To investigate the pathogenetic contribution of the several parasitic factors involved, the following procedures were performed in rats: a) regarding the role of eggs, these were isolated and injected either into the peritoneal cavity or directly into the liver parenchyma; b) for worms alone, 15-day-old infection was treated with mebendazole, killing the parasites before oviposition started; c) for both eggs and worms, rats at the 30th day of infection were treated with either mebendazole or ivermectin. Eggs only originated focal fibrosis from cicatricial granulomas, but no septal fibrosis. Worms alone induced a mild degree of perifocal septal fibrosis. Systematized septal fibrosis of the liver, similar to that observed in the infected controls, occurred only in the rats treated with mebendazole or ivermectin, with dead worms and immature eggs in their livers. Thus, future search for fibrogenic factors associated with C. hepatica infection in rats should consider lesions with both eggs and worms.

Morphometric study of the fibrosis and mast cell count in the circular colon musculature of chronic Chagas patients with and without megacolon

A morphometric study of the circular colon musculature was performed, in which the mast cell count was determined and the connective fibrous tissue in this layer was measured. The objective was to gain better understanding of Chagas megacolon morphology and contribute towards the knowledge of fibrosis pathogenesis in Chagas megas. An evaluation was made of 15 distal sigmoid rings from Chagas patients with megacolon (MCC), 15 without megacolon (CSMC) and 15 non-Chagas patients (NC). The rings were fixed in formol, embedded in paraffin, and 7mm thick sections were cut and stained using Azan-Heidenhain and Giemsa. The mast cell count and fibrosis were greater in the MCC group than in the CSMC and NC groups (p < 0.05; Kruskal-Wallis test) and there was no significant difference between the latter two. The fibrosis and increased mast cell count in the colon musculature of the MCC group possibly indicates that there is a relationship between mastocytosis and fibrosis, as has already been demonstrated in other pathologies.

Production of septal fibrosis of the liver by means of foreign protein injections into rats

Similarities and differences in antigenic humoral responses and electrophoretic patterns between Capillaria hepatica and pig-serum were investigated as a contribution to the understanding of hepatic fibrosis induced by the parenteral administration of foreign proteins. Only two out of 10 rats receiving repeated intraperitoneal injections of an extract of Capillaria hepatica-infected mouse liver presented septal hepatic fibrosis (20%). Under the same experimental conditions, 4 out of 9 rats (44.4%) developed septal fibrosis following whole pig-serum administration. Injections of normal mouse liver extracts did not result in hepatic fibrosis. Since a 100% septal fibrosis rate is observed in experimentally Capillaria hepatica-infected rats, it appeared that Capillaria hepatica products continuously released from inside the liver creates a much more effective fibrosis inducing mechanism than the parenteral administration of such factors. Thus, repeated peritoneal administration of a foreign protein to rats would not reveal the full fibrogenic potential it may have under natural conditions.

Capillaria hepatica-induced hepatic fibrosis in rats: paradoxical effect of repeated infections

Multiple exposures to parasitic agents are considered an important factor in the genesis of the most severe forms of the diseases they cause. Capillaria hepatica-induced septal fibrosis of the liver in rats usually runs without signs of portal hypertension or hepatic failure. After determining the hepatic profile of 15 animals during the course of a single infection, we submitted 20 rats to multiple Capillaria hepatica infections to determine whether repeated exposures would augment fibrosis production, transforming septal hepatic fibrosis into a true cirrhosis. Ten single-infection rats served as controls. A total of 5 exposures, with 45-day intervals, were made. Histological changes were followed by means of surgical liver biopsies, collected prior to infection and to each re-infection. Functional changes were minimal and transient. Although a slight recrudescence of fibrosis was observed after the first two re-infections and when the single-infected control group was re-infected at the end of the experiment, subsequent re-infections failed to increase the amount of fibrosis. On the contrary, there occurred quantitative and qualitative evidence of collagen degradation and suppression of parasite development. These paradoxical results are in keeping with the hypothesis that a complex immunological modulation participates in the mechanism of hepatic fibrosis induced by Capillaria hepatica infection in rats.

Role of partial hepatectomy on Capillaria hepatica-induced hepatic fibrosis in rats

It is known that hepatic fibrosis may regress following partial hepatectomy, since the hepatic parenchyma regenerates very rapidly, but not the excess of fibrous tissue. The present study evaluated this hypothesis by observing the behavior of systematized septal fibrosis induced by either 30 or 90-day-old Capillaria hepatica infection, in rats subjected to partial hepatectomy. The results revealed that the morphology of the fibrosis was unaffected, but its relative quantity within the microscope field appeared significantly decreased, as a consequence of the increased liver tissue mass following regeneration.

Clinical and ultrasound findings before and after praziquantel treatment among Venezuelan schistosomiasis patients

Abdominal ultrasound can be a useful tool for diagnosing periportal fibrosis related to Schistosoma mansoni infection, and also for planning and monitoring the evolution of hepatic morbidity following control measures. We evaluated the standardized ultrasound methodology proposed by the World Health Organization for detecting periportal fibrosis and portal hypertension, among patients from an endemic area in Venezuela, and the impact of praziquantel treatment 3-5 years later. After chemotherapy, complete reversal of periportal lesions was observed in 28.2% of the cases and progression of the disease in 5.1%. Improvement in the hepatic disease started with a reduction in the periportal thickening followed by a decrease in the size of the left hepatic lobe, spleen and mesenteric and spleen veins. Ultrasound confirmed the clinical findings after chemotherapy among the patients with reversal of the disease. However, in patients with more advanced disease, these findings were contradictory. There was no correlation between evolution of the disease seen on ultrasound and age, intensity of infection or serological findings.

Glia-Motoneuron dialogue in ALS onset and progression in SOD1G93A-mice model

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the pro-gressive loss of motoneurons (MN). Increasing evidence points glial cells as key players for ALS onset and progression. Indeed, MN-glia signalling pathways involving either neuroprotection or inflammation are likely to be altered in ALS. We aimed to study the molecules related with glial function and/or reactivity by evaluating glial markers and hemichannels, mainly present in astrocytes. We also studied molecules involved in mi-croglia-MN dialogue (CXCR3/CCL21; CX3CR1/CX3CL1; MFG-E8), as well as proliferation (Ki-67) and inflammatory-related molecules (TLR2/4, NLRP3; IL-18) and alarming/calming signals (HMGB1/autotaxin). We used lumbar spinal cord (SC) homogenates from mice expressing a mutant human-SOD1 protein (mSOD1) at presymptomatic and late-symptomatic ALS stages. SJL (WT) mice at same ages were used as controls. We observed decreased expression of genes associated with astrocytic (GFAP and S100B) and microglial (CD11b) markers in mSOD1 at the presymptomatic phase, as well as diminished levels of gap junction components pannexin1 and connexin43 and expression of Ki-67 and decreased autotax-in. In addition, microglial-MN communication was negatively affected in mSOD1 mice as well as in-flammatory response. Interestingly, we observed astrocytic (S100B) and microglial (CD11b) reactivity, increased proliferation (Ki-67) and increased autotaxin expression in symptomatic mSOD1 mice. In-creased MN-microglial dialogue (CXCR3/CCL21; CX3CR1/CX3CL1; MFG-E8) and hemichannel activ-ity, namely connexin43 and pannexin1, were also observed in mSOD1 at the symptomatic phase, along with an elevated inflammatory response as indicated by increased levels of HMGB1 and NLRP3. Our results suggest that decreased autotaxin expression is a feature of the presymptomatic stage, and precede the network of pro-inflammatory-related symptomatic determinants, including HMGB1, CCL21, CX3CL1, and NLRP3. The identification of the molecules and signaling pathways that are dif-ferentially activated along ALS progression will contribute for a better design of therapeutic strategies for disease onset and progression.

Comparison between clinical and ultrasonographic findings in cases of periportal fibrosis in an endemic area for schistosomiasis mansoni in Brazil

INTRODUCTION: Abdominal palpation and ultrasound findings among patients from an endemic area for schistosomiasis in Brazil who had been followed up for 27 years were compared. METHODS: In 2004, 411 patients from Brejo do Espírito Santo, in the State of Bahia, were selected for the present investigation after giving their written informed consent. Based on clinical data, they were divided into three groups: 41 patients with evidence of liver fibrosis in 2004 (Group 1); 102 patients with evidence of liver fibrosis in the past (1976-1989) but not in 2004 (Group 2); and 268 patients without evidence of liver fibrosis at any time during the 27-year follow-up (Group 3). All of the patients underwent abdominal ultrasound in which the examiner did not know the result from the clinical examination. The data were stored in a database. RESULTS: The prevalence of periportal fibrosis on ultrasound was 82.9%, 56.9% and 13.4% in Groups 1, 2 and 3, respectively. In the presence of hard, nodular liver or prominent left lobe and a hard palpable spleen, ultrasound revealed periportal fibrosis in 70.9%. However, periportal fibrosis was diagnosed using ultrasound in 25.4% of the patients in the absence of clinical evidence of liver involvement. Thus, ultrasound diagnosed periportal fibrosis 3.1 times more frequently than clinical examination did. CONCLUSIONS: Although clinical examination is important in evaluating morbidity due to Manson's schistosomiasis in endemic areas, ultrasound is more accurate in diagnosing liver involvement and periportal fibrosis.

Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study of liver fibrogenesis

INTRODUCTION: Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. Curative treatment of the infection prevents the development of septal fibrosis when intervention occurs up to postinfection day (PID) 15, but not later. The present investigation aimed to demonstrate which parasitic factors are present when the process of septal fibrosis can no longer be prevented by curative treatment. METHODS: Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment. RESULTS: Findings by PID 15 were compatible with the stage of complete maturation of infection, when worms and eggs were fully developed and a complex host-parasite multifocal necroinflammatory reaction showed greater intensity, but with no signs of septal fibrosis, which appeared from PID 17 onward. CONCLUSIONS: Since the worms spontaneously died by PID 15, not only septal fibrosis production, but also its maintenance and further development appeared dependent on the presence of eggs, which were the only parasitic factor remaining thereafter.

Endomyocardial fibrosis associated with mansoni schistosomiasis

Endomyocardial fibrosis (EMF) is a neglected tropical disease that affects millions of people worldwide. EMF is the most common cause of restrictive cardiomyopathy, caused by deposition of fibrous tissue on endocardial surfaces. EMF is a major cause of death in areas where it is endemic, but the pathogenesis of the disease is poorly understood. Schistosomiasis mansoni is a parasitic disease endemic in Brazil, where EMF has also been described. The association between EMF and schistosomiasis has been suggested in various publications, seeking a possible correlation between endocardial and periportal fibroses. This report describes a case of EMF associated with schistosomiasis.

Evaluation of laboratory markers of progression of HIV disease to death

INTRODUCTION: One of the important current problems in HIV/AIDS infection is the establishment of epidemiological and laboratorial prognostic parameters during patient follow-up. This study aimed at analyzing the evolution of laboratory tests: CD4 lymphocyte count, viral load, hemoglobin (Hb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the epidemiological variables sex and age as prognostic factors for survival in progression to death among AIDS patients. METHODS: A retrospective study was conducted using analysis of medical records, and prospective 24-month follow-up of patients with HIV/ AIDS attended at the President Vargas Hospital Outpatient Clinic, a reference center in HIV/ AIDS attendance in the State of Maranhão, Brazil. The study analyzed patients aged 10 to 60 years old, who manifested AIDS and who were not using antiretroviral therapy or had used it for less than 5 years. The Chi-square test was used for statistical analysis. RESULTS: The sample included 100 patients - 57 were current outpatients, and 43 had died. The variables viral load (p=0.726), ALT (p=0.314), sex (p=0.687), and age (p=0.742) were analyzed, and no evidence of association between them and worst prognosis was observed. CONCLUSIONS: A significant relation was verified between low Hb levels (p=0.000) and CD4 (p=0.000) and shorter survival.

Treatment and education reduce the severity of schistosomiasis periportal fibrosis

Introduction This study evaluates the factors associated with the development of severe periportal fibrosis in patients with Schistosoma mansoni. Methods A cross-sectional study was conducted from April to December 2012 involving 178 patients infected with S. mansoni who were treated in the Hospital das Clínicas of Pernambuco, Brazil. Information regarding risk factors was obtained using a questionnaire. Based on the patients' epidemiological history, clinical examination, and upper abdomen ultrasound evaluation, patients were divided into 2 groups: 137 with evidence of severe periportal fibrosis and 41 patients without fibrosis or with mild or moderate periportal fibrosis. Univariate and multivariate analyses were conducted using EpiInfo software version 3.5.5. Results Illiterate individuals (30.1%) and patients who had more frequent contact with contaminated water in towns in the Zona da Mata of Pernambuco (33.2%) were at greater risk for severe periportal fibrosis. Based on multivariate analysis, it was determined that an education level of up to 11 years of study and specific prior treatment for schistosomiasis were preventive factors for severe periportal fibrosis. Conclusions The prevailing sites of the severe forms of periportal fibrosis are still within the Zona da Mata of Pernambuco, although there has been an expansion to urban areas and the state coast. Specific treatment and an increased level of education were identified as protective factors, indicating the need for implementing social, sanitary, and health education interventions aimed at schistosomiasis to combat the risk factors for this major public health problem.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction.