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Cellular localisations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha mRNA in a parasitic granulomatous disease of the liver, alveolar echinococcosis.

Alveolar echinococcosis (AE), an uncommon and very severe parasitic liver disease, can be considered as an "infectious model" of granulomatous disease, where cellular immunity plays a key role in the defence against Echinococcus multilocularis, the larval cestode responsible for the disease. We analysed the localisation of the expression of the pro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha mRNA in human AE liver lesions, in the periparasitic granulomas and in the hepatic parenchyma, as well as the phenotypic characteristics of the cells on serial sections. In situ hybridizations, using anti-sense 35S dUTP-labeled IL-1 beta, IL-6 and TNF-alpha riboprobes, were performed on cryostat liver sections; the sense probes were used as negative controls. IL-1 beta, IL-6 and TNF-alpha mRNA were observed in macrophages located at the extreme periphery of the granuloma, between the lymphocytic ring and the liver parenchyma, in patients with active AE. No cytokine mRNA expression was observed in a patient with an abortive case. Only TNF-alpha mRNA was located in the periparasitic area, in cells morphologically identified as macrophages but exhibiting an unusual phenotype (CD 11b-, CD 25+); this particular expression was observed only in those patients with very fertile lesions, associated with centro-granulomatous necrosis. These results show that pro-inflammatory cytokines are consistently produced by macrophages at the periphery of the periparasitic granuloma and can serve as mediators of acute-phase protein secretion and of fibrogenesis in that location.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radiological manifestations of liver and gastrointestinal parasitic infections.

There is a wide variation in the prevalence of parasitic diseases in different countries, particularly in the Tropics. The clinical status of affected patients varies from normal to severe ill health. Radiology has acquired a major role in the diagnosis and, in some instances, the management of a significant variety of parasitic infections. Plain films, ultrasound, computed tomography and magnetic resonance imaging, together with the help of clinical and laboratory tests, can reach a diagnosis with a high percentage of accuracy.

Diagnostic Imaging↗

Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-alpha and early death in C57BL/6 mice.

To address the question of how the murine host responds to a prototypic type 1 cytokine inducer while concurrently undergoing a helminth-induced type 2 cytokine response, C57BL/6 strain animals with patent schistosomiasis mansoni were orally infected with the cystogenic Toxoplasma gondii strain ME49. Schistosoma mansoni infection resulted in a significantly higher mortality rate when mice were subsequently orally infected with ME49, and these animals displayed a defective IFN-gamma and NO response relative to animals infected with T. gondii alone. Plasma levels of TNF-alpha and aspartate transaminase in double-infected mice were greatly elevated relative to mice infected with either parasite alone. Consistent with the latter observation, these animals exhibited severe liver pathology, with regions of coagulative necrosis and hepatocyte vacuolization unapparent in mice carrying either infection alone. Interestingly, mean egg granuloma size was approximately 50% of that in mice with S. mansoni infection alone. The exacerbated liver pathology in coinfected mice did not appear to be a result of uncontrolled tachyzoite replication, because both parasite-specific RT-PCR analysis and immunohistochemical staining demonstrated a low number of tachyzoites in the liver. We hypothesize that mortality in these animals results from the high level of systemic TNF-alpha, which mediates a severe liver pathology culminating in death of the animal.

Animals↗

Liver involvement in human schistosomiasis mansoni. Regression of immunological and biochemical disease markers after specific treatment.

Peripheral blood cholyglycine and procollagen-III-peptide were measured in 22 Zairean patients with hepatomegaly caused by S. mansoni before and after treatment with praziquantel. Circulating T-cell subsets and cutaneous in vivo delayed type hypersensitivity were assessed; serum neopterin and beta 2-microglobulin served as indicators for macrophage/lymphocyte activation. The results were compared to age and sex matched patients with S. mansoni infection limited to the intestinal tract and schistosomiasis free controls with equal socioeconomic background. Abnormal serum cholyglycine and neopterin levels and alterations of circulating T-cell subset frequencies were associated with hepatomegaly in schistosomiasis. Normalization of these parameters reflected a regression of egg-induced immunopathology as early as two months after specific chemotherapy. Serum procollagen-III-peptide concentrations rose significantly after treatment, suggesting release of propeptide previously incorporated without cleavage into tissue collagen. The combination of these biochemical and immunological parameters may allow assessment of the pathophysiological mechanisms responsible for liver disease in individual patients.

Adolescent↗

[Influence of anesthesia on the localization of Schistosoma mansoni. Intestinal schistosomiasis in white mice].

General anesthetics or hypnotics (ketamine, propanidid, thiopental, althesin, halothane, enflurane, ether), were tested on white mice infested with Schistosoma mansoni to study possible changes in the migration of this trematode from the mesentery to the liver. With this in mind, populations of 25 mice of the same sex and age were chosen at random; they were divided into a control group and a group submitted to an anaesthetic agent. The mice were perfused after dissection and catheterization of the abdominal aorta. A vacuum-pump was used to collect separately the parasites from the mesenteric and portal vessels and those from hepatic vessels. The parasite counts in the hepatic vessels of the mice which had received an anesthetic were compared with those found in the vessels of the control group; they were found to be significantly raised. It would appear that anesthetic agents altered the neuromuscular function of the parasite which was thus carried away towards the liver. This massive migration of the parasites would deprive the hepatic lobules of portal blood by worsening the already existing obstruction at the precapillary level caused by the schistosomiasis.

Anesthetics↗

Pathology and course of natural Schistosoma japonicum infection in pigs: results of a field study in Hubei province, China.

In order to obtain information on the natural course of porcine infection with Schistosoma japonicum, pigs were exposed to the cercariae of this parasite in a highly endemic region of China. Five, 5-month-old pigs previously infected with S. japonicum (group A) and 10, schistosome-naïve piglets (group B) were allowed on a pasture infested with Oncomelania snails for one transmission period (approximately 5.5 months). All the piglets rapidly acquired infection, and both groups remained infected throughout the study period. Group B showed fever, diarrhoea and anorexia in the early egg-excretion phase, and marked growth reduction. In both groups, post-mortem examination revealed live schistosomes and lesions associated with dead worms in the intestinal and mesenteric vasculature, and egg-related pathology in the large intestine and liver. Major findings were exudative lesions connected with egg excretion in the intestine, and granulomatous obstruction of portal veins in the liver. Signs of granuloma modulation were found in the liver, but not in the intestine. In conclusion, the study showed that field exposure of pigs to S. japonicum for one transmission period resulted in clinical disease and growth retardation in the youngest pigs, and significant pathology in both groups. Self cure, prominent in experimental porcine infections produced with single, high-dose inocula, was not induced in either group.

Animals↗

[Natural infection of wild rodents by Schistosoma mansoni].

UNLABELLED: In Planalto, a small locality in the interior of the Bahia state, Brazil, 47% of sylvatic rodents were found to be naturally infected with Schistosoma mansoni, whereas the prevalence of the infection in the inhabitants of the area was 3.26%. The rodents (Nectomys) live near the houses, in contact with water, passing viable schistosome eggs in the stools. Worm burden is variable amongst such rodents. Periovular granulomas are small, especially in liver and intestines, and hepatic fibrosis is mild or absent, with no morphological evidence of portal hypertension being noted. Miracidia isolated from the eggs recovered from Nectomys readly infected laboratory-raised Bahia strain of Biomphalaria glabrata. Cercariae then obtained infected Swiss mice in a similar way as the human strains of S. mansoni kept in laboratory. Also, Swiss mice left in contact with water collections in Planalto were easily infected, which proved the transmissibility potential of the area. IN CONCLUSION: sylvatic rodents found in the area of Planalto tolerate well S. mansoni infection, eliminate viable eggs in the stools, are usually infected with a strain probably of human origin and therefore may play a role in maintaining parasite cycle in the area.

Animals↗

Large-scale management systems and parasite populations: coccidia in rabbits.

Broiler rabbit production has become an important branch of animal protein and fur production, not only in the traditionally rabbit breeding and consuming countries, but recently in many other countries of the world. The profitability of the rabbit industry is dependent primarily on the good feed conversion. Aspects of this include factors such as morbidity and mortality of infections, adequate knowledge and fulfilment of both accommodation and nutritional requirements, appropriate breeding systems, etc. There is much controversy about the role of coccidia in the losses of intensified rabbit breeding enterprises. There is no doubt about the significance of Eimeria stiedai which may cause condemnation of large amounts of liver as a result of infection in rabbit colonies of small holders. However, this parasite is rare in large scale rabbit farms. In the latter, intestinal coccidiosis is most frequently--although not invariably--incriminated either as a primary or more often as a predisposing factor of intestinal enteropathies causing severe mortality, mainly in the early post-weaning period. The ability to isolate and maintain species of Eimeria in specific pathogen-free (SPF) rabbits has made it possible to characterize them, such as the most pathogenic E. intestinalis and E. flavescens: the pathogenic E. magna, E. irresidua and E. piriformis; and the least pathogenic E. perforans, E. neoleporis (syn. of E. coecicola) and E. media species. Prophylactic measures are dealt with briefly, and laboratory and field trials with the currently most promising rabbit anti-coccidial drugs (Lerbek, robenidine and salinomycin) are dealt with in more detail.

Animals↗

Caerulomycin, an antifungal antibiotic with marked in vitro and in vivo activity against Entamoeba histolytica.

The anti-amoebic action of the bipyridyl antibiotic caerulomycin was assessed in vitro and in vivo using various strains of Entamoeba histolytica from polyxenic, axenic and monoxenic cultures. Minimum inhibition concentrations of caerulomycin (metronidazole) were 7.5 (5), 15.6(1.95) and 60 (2.5) micrograms/ml against polyxenic, axenic and monoxenic cultures of E. histolytica, respectively. The ED50 values ascertained in golden hamsters (extraintestinal amoebiasis) and rats (intestinal amoebiasis) after the oral route were 136 and 199 mg/kg (X4), respectively. Metronidazole proved to be approximately four times more active against tissue forms of E. histolytica than caerulomycin [ED50 of metronidazole: less than 40 mg/kg (X4)]. The antibiotic was slightly superior to metronidazole in its action on lumen forms of E. histolytica [ED50 of metronidazole: 233 mg/kg (X4)]. The antibiotic was in some cases toxic to hamsters and rats within the therapeutic range.

2,2'-Dipyridyl↗