Repeated infections with Schistosoma mansoni and liver fibrosis in undernourished mice.

The mouse model of schistosomal periportal fibrosis (Symmers' "pipestem" fibrosis), that develops in 30-50% of the infected animals, is not reproduced in undernourished mice. Host nutritional status is likely to be a variable that may influence the outcome and progression of infection, since it interferes with the dynamics of connective tissue changes occurring in chronic hepatic schistosomiasis. Re-infections increase the occurrence of periportal liver fibrosis in well-nourished animals, but it is not known how undernourished mice would behave being repeatedly re-infected. So, 21-day-old male albino Swiss mice were individually exposed to 30 cercariae (percutaneous route) of the BH strain of Schistosoma mansoni, 4 weeks after being on a low-protein diet. Control animals were fed on a commercial balanced chow for mice. The nutritional status was evaluated by body weight gain and measurement of food intake. Mice were divided into four groups: A1 (undernourished, single infected), A2 (well-nourished, single infected), B1 (undernourished, re-infected), B2 (well-nourished, re-infected). The primary infection was performed 4 weeks after ingesting the respective diet. Re-infections started 45 days later, with exposure to 15 cercariae, at 15 day intervals. Mice were sacrificed 18 weeks after the primary exposure. The livers were submitted to morphological (gross and microscopic pathology), morphometric (percentage of fibrosis; granuloma size; volume and numerical densities) by using semi-automatic morphometry, and biochemical (quantification of collagen as hydroxyproline) studies. Worm burdens and hepatic egg counting were also recorded. Values for body weight gains were always lower in undernourished mice, the effects of re-infection being minimal on this regard. Liver and spleen weights were higher in well-nourished mice (either single infected or re-infected) and mainly related to the type of ingested diet. A greater number of re-infected well-nourished mice developed periportal fibrosis, but undernourished re-infected animals did not reproduce this lesion. The percentage of fibrosis and hepatic collagen content were higher in well-nourished mice, but differences between single infected and re-infected groups were not statistically significant.

Correlation between interleukin-10 and in situ necrosis and fibrosis suggests a role for interleukin-10 in the resolution of the granulomatous response of tuberculous pleurisy patients.

In order to identify mediators involved in immune-mediated disease regression, the pleural cytokine and histopathological profile was evaluated in tuberculous pleurisy patients with varied disease duration and clinical presentation, previous to chemotherapy. Interleukin (IL)-10, interferon (IFN)-gamma and tumor necrosis factor (TNF) levels in pleural fluids were shown to decrease with disease time. IL-10 was positively correlated with IFN-gamma, TNF and necrosis area in pleural sections. To parallel these findings with disease regression, individuals showing fever, anorexia, and progressive exudate in the pleural cavity (active disease) were compared with patients without symptoms and with a decrease in exudate volume (regressive disease). IFN-gamma and TNF levels were lower in regressive disease, as well as reduced necrosis area in pleural sections. Our results indicate that tissue destruction and a prominent Th1 response mark the early phase of tuberculous pleurisy and suggest that down-modulation of this response, with the possible participation of IL-10, is associated with disease resolution.

Morphological assessment of the behavior of three-dimensional anionic collagen matrices in bone regeneration in rats.

The osteogenic behavior of three-dimensional collagenic and anionic matrices (M3DGA) implanted in critical bone defects of 8 mm diameter was morphologically assessed. The defects were performed in the calvaria of 48 adult male (Wistar) rats, and observed at days 15, 30, and 60. The animals were distributed in four groups of equal number: GA1 (M3DGA with 60 min of cross-linking in glutaraldehyde [GA]); GA2 (M3DGA with 30 min of cross-linking in GA); GA3 (M3DGA with 15 min of cross-linking in GA); and G4 (control group, without any implanted biomaterial). The M3DGAs were biocompatible, with mild and regressive chronic granulomatous inflammation, associated with the degradation of their fibers. Furthermore, tissue neovascularization and neomineralization was noted, with statistically significant differences in these amounts among the groups (GA1, GA2, and GA3) and G4. In G4 neoformation was limited to the edges of the defect as well as interstitial fibrosis. Under the experimental conditions and for the parameters analyzed, the M3DGAs had osteogenic behavior, which was more evident in M3DGA 15 min.

Morphological signs of cirrhosis regression. Experimental observations on carbon tetrachloride-induced liver cirrhosis of rats.

Regression of hepatic cirrhosis is a controversial issue. Recently, a list of histopathological features, observed in human material, was suggested as a hallmark of cirrhosis in the process of regression. An investigation for the presence of these morphologic features was performed at monthly intervals in rats with proved carbon tetrachloride (CCl4)-induced cirrhosis over a period of 9 months following discontinuation of treatment, using sequential liver biopsies. Within the first 4 months, features of the "hepatic repair complex" were identified, together with the enlargement of the hepatic nodules and thinning of the fibrous septa. Subsequent to the 4 months, the histological picture, composed of large and inconspicuous nodules and delimited by thin and frequently incomplete fibrous septa "incomplete septal cirrhosis", appeared to be stabilized. These fibrous septa, when injected with India ink from the portal trunk, presented blood vessels that were seen to drain directly into the sinusoids. These findings suggested that when the cause of cirrhosis is removed, the liver may adapt itself to a new and permanent structure, probably compatible with normal or near-normal function, which may render hepatic cirrhosis clinically, although not morphologically, reversible.

Morphometric study of Schistosoma mansoni adult worms recovered from Undernourished infected 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.

Pathology of intracardiac nerves in experimental Chagas disease.

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.