Biomedical subjects

Z A Andrade

Publications and source records attributed to Z A Andrade.

At least 37 records · Page 2Linked to original sources

PubMed1998

Role of the spleen on the pathogenesis of schistosomal periportal (pipestem) fibrosis of the liver: an experimental approach.

Splenectomized and sham-operated mice with chronic Schistosoma mansoni infection were compared for the development of periportal fibrosis (pipestem fibrosis). Although this lesion appeared less frequently in splenectomized mice, it also developed in the absence of the spleen. The time of splenectomy, spleen weight, presence of anti-idiotypic antibodies, the number of eggs in the liver, and the type and size of periovular granulomas in the liver as evaluated by computerized morphometry did not show statistically significant differences between the two groups. It is concluded that the role of the spleen in the development of pipestem fibrosis seems ancillary and that multifactorial influences, including worm burden, hepatic vascular adjustment, and factors associated with the biology of extracellular matrix of the liver, probably play a more significant role.

Animals↗

PubMed1997

Pathogenesis of schistosomal 'pipestem' fibrosis: a low-protein diet inhibits the development of 'pipestem' fibrosis in mice.

Mice maintained on a low protein diet for 30 days and then infected with Schistosoma mansoni for 16 weeks completely failed to develop 'pipestem fibrosis' of the liver, whereas 50% of well nourished controls did. Usually mice with relatively mild and prolonged S. mansoni infection develop two different pathological pictures: one consisting of disseminated portal fibrosis caused by periovular granulomas concentrated at the portal spaces (pipestem fibrosis), the other represented by scattered hepatic granulomas. The reason for this dual response is poorly understood. Combined results from parasitological, histopathological, biochemical and morphometric data revealed that peri-ovular granulomas of undernourished mice were smaller, inflammation was less intense and there was minimal fibrosis in comparison with those of controls, which suggest that a vigorous host response is necessary for the pathogenesis of schistosomal portal fibrosis.

Animals↗

PubMed1997

Influence of treatment with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi.

Latent Trypanosoma cruzi infection may be reactivated in immunosuppressed individuals, with unusual clinical patterns, such as meningoencephalitis, pseudo neoplastic lesions in the central nervous system, and myocarditis with numerous parasites in the heart muscle. To investigate this problem 68 Swiss mice chronically infected with different strains of T. cruzi were treated with different combinations of immunosuppressive drugs (azathioprine, cyclosporine and betamethasone), in such a way as to imitate the situation during post transplantation treatment. Mortality varied from 6 to 25% in treated mice. There were no deaths in untreated controls. Normal mice have been submitted to the same schedules of immunosuppression as controls of treatment and no deaths were registered during treatment. Chronically infected mice showed significant elevation of total number of leukocytes and lymphocytes in comparison with intact controls; a significant decrease in blood leukocytes and lymphocytes occurred post-treatment in two of the treated experimental groups. Exacerbation of myocarditis and myositis and a high incidence of brain lesions, with focal necrosis, granulomatous lesions and glial proliferation even in the absence of parasites were present in immunosuppressed mice but not in infected controls. Although differing in some aspects from Chagas' disease in immunosuppressed humans, the murine model did show some features that resembled it, especially the peculiar pattern of central nervous system involvement.

Animals↗

PubMed1997

The indeterminate phase of Chagas' disease: ultrastructural characterization of cardiac changes in the canine model.

The indeterminate phase of Chagas' disease is defined as the prolonged period of clinically silent infection that follows the phase of acute primary infection with Trypanosoma cruzi. The dog is the only experimental animal model in which the indeterminate phase progresses to the late phase of severe, chronic myocarditis. This report describes the cardiac histologic and ultrastructural findings in dogs that survived the acute phase of infection with T. cruzi, becoming clinically and electrocardiographically normal for up to 3.5 years, while maintaining positive serologic test results during this period of time. Most of the myocardium appeared morphologically normal; however, small foci of mild, chronic myocarditis were present, with interstitial edema, mild fibrosis, and infiltration by lymphocytes, macrophages, and plasma cells. No microvascular lesions and no areas of close contact between immune effector cells and endothelial cells or cardiac myocytes were present. These findings were in sharp contrast to those observed in the canine model during the acute infection with T. cruzi. In this model, acute myocyte damage and lesions in the microcirculation, including fibrin microthrombi, were associated with close contacts between immune effector cells and myocytes or endothelial cells. Focally inflamed interstitial tissue showed increased deposition of amorphous and collagenous extracellular matrix as well as evidence of breakdown of collagen. The features of the inflammatory cells in the indeterminate phase of Chagas' disease were interpreted as indicating a self-limited cycle of focal inflammatory changes, with modulation and suppression of cell-mediated immune responses. Thus, we consider the indeterminate phase of Chagas' disease to be a stage of host-parasite equilibrium rather than a process of progressive damage.

Animals↗

PubMed1996

[Clinico-pathological correlation in the indeterminate form of experimental Chagas' disease in dogs].

PURPOSE: To study the functional cardiac component of the indeterminate form of experimental Chagas' disease in dogs. METHODS: Four dogs chronically infected with Trypanosoma cruzi and eight normal controls were used. They were submitted to several invasive procedures, either in the presence of complete autonomic block or not, to test for disturbances in the origin and conduction of electric stimuli and the function of cardiac muscle. Histological examination of the heart and its conduction systems was performed in all animals. RESULTS: Mild to moderate focal myocarditis was found in infected dogs, often involving the conduction system of the heart. Sections of the heart from control dogs were histologically normal. Functional data on excitability, intra and interatrial conduction time and sinus node recovering time were essentially similar for both infected and control animals. CONCLUSION: Focal myocarditis, the hallmark of the indeterminate form of Chagas' disease, did not alter the normal parameters of cardiac function, as seen after investigation with sensitive invasive techniques. It is probable that subjects considered as belonging to the indeterminate form of Chagas' disease, but presenting mild alterations at sensitive exploratory tests, may have more severe lesions than that usually described or may be already in the early progressive cardiac form of the disease.

Animals↗

PubMed1995

Chronic hepatitis in experimental schistosomiasis.

Histological features of chronic active and chronic persistent hepatitis were observed in mice, rabbits and non-human primates infected with either Schistosoma mansoni and Schistosoma japonicum. In early infection hepatitis appeared as a reactive change due to liver damage caused by the deposition of schistosome eggs, but portal and septal cellular infiltrations tended to remain long after parasite aggression had diminished or disappeared, either spontaneously with time or after chemotherapy. In rabbits, and to a lesser degree in monkeys, a picture of chronic active hepatitis was present, with evolution to cirrhosis in the former. The experimental findings indicate that schistosomiasis has the potential to induce chronic hepatitis and suggest that the current assumption that chronic hepatitis seen in humans with schistosomiasis is always due to concomitant viral infection should be reviewed.

Animals↗

PubMed1994

Dynamics of connective matrix deposition in acute experimental E. coli pyelonephritis in rats.

Adult male rats were subjected to pyelonephritis by direct kidney intramedullary injection of 0.1 ml saline suspension of 10(5) E. coli. Animals were killed at intervals of 4, 10, 15, 30 and 60 days. Half of each kidney and bladder were cultured in proper bacteriologic media to demonstrate the existence of infection. The other halves were submitted to light microscopy and ultrastructural studies. Immunofluorescence methods were used for the study of connective matrix components, at the initial stage of the inflammatory process (4, 10 and 15 days). Infection was documented by bacteriologic, gross and microscopic findings in all groups following inoculation, and it lasted up to two months. Following the acute inflammatory reaction, fibronectin and type III collagen were deposited in the interstitium of kidneys. Small amounts of type I collagen were found later. Type IV collagen appeared in small quantities, associated with collapse of structures containing basement membranes. Fibronectin became concentrated in re-activated foci. The subsequent scarring and associated focal renal atrophy depended upon the extension of the acute lesion.

Animals↗

PubMed1994

Stromal collapse in acute atrophy of lymphoid organs.

The formation of post-collapse fibrosis was investigated in lymphoid tissues of rats simultaneously treated with cyclophosphamide and betamethazone. Effectiveness of treatment was monitored by means of peripheral blood smears. Animals were sacrificed 1, 2, 3, 4, and 7 days after the last injection. Fragments of lymph nodes and thymus were studied by light and electron microscopy. Compared with untreated controls, lymphoid organs from treated animals revealed considerable reduction in the number of cells and condensation of the stroma. Picrosirius-red stained slides seen under polarized light revealed the condensed stroma to contain mainly collagens. Electron microscopy confirmed the presence of collapsed collagen fibrils in the absence of signs of functional activation of the connective tissue cells within the collapsed areas. This investigation shows that a pure form of collapse fibrosis can be observed in lymph nodes and thymus following sudden atrophy of lymphoid cells.

Animals↗

PubMed1994

Reversal of advanced liver fibrosis in rabbits with Schistosomiasis japonica.

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.

Animals↗

PubMed1994

Extracellular matrix degradation in parasitic diseases.

1. Fibrosis is an important manifestation of several parasitic diseases, but is not irreversible. A marked degree of extracellular matrix degradation can occur after cure of parasitism. Patients with the hepatosplenic form of schistosomiasis undergo considerable resorption of portal fibrosis months or years after curative treatment as demonstrated by ultrasonography and pathological examination. 2. Studies of the post-treatment degradation of extracellular matrix in schistosomal periovular granulomas have demonstrated two forms of collagen degradation: in hepatic granulomas formed during early infection a rapid process occurs, with the extracellular breakdown of fibers and internalization of collagen fragments, whereas during late infection, degradation is slow and is accompanied by focal electrondense and/or lytic changes. 3. Extensive extracellular matrix degradation and resorption occurring after curative treatment was recently described in the liver of a man with advanced visceral leishmaniasis and in the heart of mice with chronic Chagas' disease.

Animals↗

PubMed1994

Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease.

Animals↗

PubMed1993

Role of fat-storing cells in schistosomal hepatic fibrosis of mice.

The involvement of fat-storing cells (FSC) in hepatic schistosomal granuloma was investigated in mice infected with Schistosoma mansoni cercariae. After infection, 24 animals were treated with s.c. injections of vitamin A in a total dose of 210,000 IU given twice a week for 3 weeks. Two other groups of 24 animals each were: a) non-infected vitamin A-treated animals and (b) untreated infected controls. Animals from all groups were killed at weekly intervals from the 5th through the 10th week following infection. Pieces of liver were examined by light microscopy and transmission electron microscopy. In all vitamin A-treated animals, FSC disclosed prominent cytoplasmic fat droplets, which permitted their prompt identification in the light and in the electron microscope. They were found in large numbers as a constituent of periovular granulomas. In infected controls, FSC were not identified in granulomas, possibly because lipid droplets disappeared during differentiation to the fibroblastic phenotype. FSC also appeared within areas of septal fibrosis. These data suggest that FSC play an important part in focal portohepatic fibrosis during granuloma formation around S. mansoni eggs in the liver of mice.

Adipocytes↗

PubMed1993

Biology and pathology of Schistosoma mansoni and Schistosoma japonicum infections in several strains of nude mice.

Schistosoma mansoni and S. japonicum infections in nude mice (nu/nu) were compared with infections in nu/+ heterozygotes or intact mice. Seven to 12 weeks after exposure to S. mansoni, the responses of Swiss NCR, C3H, BALB/c and C57B1/6 nude mice did not differ substantially. Nude mice of all these strains showed minute granulomas around eggs in the liver and minimal hepatic fibrosis. Microvesicular and necrotizing changes in hepatocytes were similar in all mouse strains, and S. mansoni infections were frequently lethal to nude, but not to intact mice between the seventh and ninth weeks of infection. Nude mice that survived the ninth week of infection generally lived until the 12th week. The number of eggs per mature worm pair in the tissues of S. mansoni-infected nude mice was similar to the number in intact mice, but nude mice passed fewer eggs in the feces. Nude mice that received serum from infected intact mice excreted eggs in the stool in numbers equivalent to intact mice, but continued to form minute granulomas around S. mansoni eggs. Reconstitution with fetal thymus or with splenocytes from normal or S. mansoni-infected mice partially or completely restored hepatic granuloma size, granuloma eosinophils, hepatic fibrosis, and excretion of eggs in the feces. In contrast to S. mansoni infection, S. japonicum infections in nude mice did not cause necrosis of hepatocytes or excessive mortality, and S. japonicum eggs were passed in the feces in numbers equivalent to those passed by infected intact mice.

Animals↗

PubMed1993

Regression of hepatic lesions after treatment of Schistosoma mansoni or Schistosoma japonicum infection in mice: a comparative study.

Experimental infections with Schistosoma mansoni and S. japonicum differ in several aspects and post-treatment resorption of fibrosis might be one of them. To investigate this point, mice infected with each of these schistosome species were treated with praziquantel and the evolution of hepatic lesions was sequentially followed for five months. Parasitologic data showing destruction of worms and eggs and biochemical findings of progressively decreased collagen concentration after cure indicated that the lesions caused by S. mansoni and S. japonicum involuted in a similar fashion following chemotherapy. The time sequence of the histologic changes indicative of decreasing inflammation and progressive matrix degradation and resorption was also similar in both cases.

Animals↗

PubMed1993

Characterization of the murine model of schistosomal hepatic periportal fibrosis ('pipestem' fibrosis).

During mild (one to two pairs of worms) and prolonged (23 weeks or more) mouse infections with Schistosoma mansoni, but not with S. japonicum, periovular granulomas and fibrosis were seen to be preferentially located along periportal tissues. This caused fibrotic expansion of the portal spaces on a background of normal-looking hepatic parenchyma, a picture mimicking 'clay pipestem fibrosis' seen in human patients with advanced schistosomiasis. The model was reproduced in outbred and in several strains of inbred mice, and their main characteristics were studied and compared to the human counterpart. A balanced consideration of the similarities and differences between the murine model and human pipestem fibrosis is needed for the adequate utilization of this simple, reproducible and inexpensive experimental model.

Animals↗

PubMed1992

Hepatic connective tissue changes in hepatosplenic schistosomiasis.

Destruction of intrahepatic portal vein branches with dispersion of smooth muscle cells into the periportal fibrosis and preservation of arterial and ductal structures were the main characteristic findings seen in 66 surgical liver biopsies from patients with the hepatosplenic form of schistosomiasis. Besides these diagnostic features, the present histologic, immunocytochemical, and ultrastructural study revealed the presence of a complex matrix forming the portal and septal fibrosis in advanced schistosomiasis. There was marked hyperplasia of elastic tissue, presence of several collagen isotypes (I, III, procollagen III, IV, and V), actin, desmin, fibronectin, and laminin in a richly vascularized connective tissue. Signs of multifocal matrix (collagen) degradation were observed both at light and electron microscopic levels, suggesting a predominance of a fibrolytic process, at the time parasite-related lesions had almost disappeared. The latter findings are related to the involution of periportal fibrosis now being observed in patients who have undergone antischistosomal chemotherapy. They exemplify morphologic changes connected with chronic collagen degradation in human schistosomiasis that are similar to those first seen in experimental material. Evidence of either persistent or active chronic hepatitis was seen in several cases but its etiology could not be determined.

Adolescent↗

PubMed1992

Morphological aspects of early and late collagen degradation in granulation tissue.

A sequential histologic, ultrastructural and immuno pathologic study was carried out in the Selye's inflammatory pouch model to observe extracellular matrix and cellular changes during granulation tissue formation. Besides changes involving different components of the connective tissue, it was observed that collagen resorption occurred under a biphasic process. At an early phase (3rd to 15th day), in which exudative inflammatory changes predominated, signs of collagen synthesis and degradation were seen simultaneously. Extracellular breakdown and internalization of collagen fragments within fibroblasts and myofibroblasts were observed. Later on (30th to 60th day), changes affecting collagen had a different ultrastructural appearance. Collagen fragmentation, focal "lytic" and "electron dense" changes occurred in the extracellular space specially at the periphery of fibroblasts, myofibroblasts and smooth muscle cells. Collagen degradation, thus seems to be a continuous process in granulation tissue, occurring with different morphologies at different times.

Animals↗

PubMed1992

Morphological features of collagen degradation in advanced hepatic schistosomiasis of man.

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections taken from patients with periportal ("pipe-stem") fibrosis caused by schistosomiasis mansoni. Besides the presence of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of smooth muscle fibers following the destruction of portal vein branches. Ultrastructural changes represented by focal lytic and/or electron dense alterations of collagen fibrils were similar to those first seen in experimental material and designated as "chronic collagen degradation". Elastin and related microfibrils were also affected by focal condensation, fragmentation, distortion and dissolution. Schistosome eggs were scanty in the tissue sections examined. Matrix degradation represented involuting changes related to the progressive diminution of parasite aggression, which occurs spontaneously with age or after cure by chemotherapy. Changes of focal matrix degradation now being described represent the basic morphological counterpart of periportal fibrosis involution documented clinically, especially by ultrasonography, in patients with hepatosplenic schistosomiasis submitted to curative chemotherapy.

Adolescent↗