Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HSS represents a special model of intrahepatic portal hypertension characterized by a presinusoidal portal block and a well-preserved liver parenchyma. Symmers' fibrosis appears in a small but significant proportion of patients with a high worm load. Its pathogenesis is not well established, although experimental and clinical studies point to egg granulomata as the main pathogenetic factor. The eggs carried continuously through the portal circulation produce inflammation and gross amputation of the intrahepatic veins, portal and periportal granulomas, and, eventually, a coarse perilobular fibrosis ("pipe-stem"). Portal hypertension, esophageal varices, and hepatosplenomegaly are the main consequences of these morphologic changes. Gastrointestinal bleeding is the most frequent cause of death. Unlike in cirrhosis, advanced liver failure is not seen except when HSS is associated with liver lesions from other causes such as virus and alcoholism. Helminthiasis treatment is based on chemotherapy with praziquantel or oxamniquine. Bleeding esophageal varices are managed by sclerotherapy or surgical procedures. Splenectomy with gastroesophageal devascularization seems to be the best choice.
 ...
PMID:Hepatosplenic schistosomiasis. Pathophysiology and treatment. 156 71

The effect of cyclosporin A (CsA) on schistosomal nephropathy in infected mice with Schistosoma mansoni (S. Mansoni) has been investigated. Infected mice were orally treated with 50 mg/kg body weight of CsA for 5 consecutive days at the 8th, 12th, 16th week postinfection (p.i.). Four weeks after drug therapy, CsA aborted and retarded the progression of glomerular injury in all stages of the disease; particularly with early drug therapy. This was evidenced by the reduction in electron dense deposits and weak positivity by fluorescent microscope. This response was accompanied by amelioration of hepatosplenomegaly. The effects of CsA could be related to its known immunosuppressive effect on T-helper (Th) cells. Moreover, CsA had a profound anti-schistosomal activity as demonstrated by the significant decrease in worm burden specially female worms, and the increase in the percentage of mature and dead eggs in intestinal mucosa in this study. So, CsA would ameliorate the glomerular lesion in early stages of schistosomal nephropathy, mainly by its immunosuppressive effect, but in later stages, the direct anti-schistosomicidal effect would take the upper hand.
 ...
PMID:Schistosomal nephropathy: effect of ciclosporin A (CsA) in murine schistosomiasis mansoni. 157 69

Schistosomiasis mansoni is a chronic helminthic disease that affects about 100 million people in the tropics. The worms have a life span of 5 to 10 years, and they live in the mesenteric veins of the host. Lightly infected individuals are asymptomatic or manifest mild intestinal symptoms. Heavily infected individuals often develop severe morbidity with hepatosplenomegaly, sometimes with a fatal outcome. Morbidity is attributed to the strong humoral and T-cell-mediated host immune responses developed to a variety of parasite antigens and expressed as tissue inflammations. The immunopathology includes dermatitis, immune complex-mediated kidney disease, and, chiefly, T-cell-mediated granuloma formation and fibrosis around disseminated parasite eggs. This review describes the mechanisms of induction and expression of immunopathology in infected persons and experimental animals. Immunoregulatory mechanisms that modulate the enhanced immune responses and may ameliorate excessive morbidity are discussed.
 ...
PMID:Immunopathology of Schistosoma mansoni infection. 250 81

Ciclosporin A (CsA), administered subcutaneously as 5 daily injections of 50 mg.kg-1, reduced the numbers of Schistosoma mansoni perfused from MF1 mice at 7 weeks post-infection. The timing of drug administration revealed that the antischistosomal effects were greater when CsA treatment coincided with or was within a few days of infection with the parasite. CsA exerted a clear prophylactic effect, which decreased with time and was virtually abolished by 4 months pre-infection. Adult worms treated in vivo were partially susceptible to CsA. In addition to its antiparasite action, CsA reduced hepatosplenomegaly due to schistosomiasis and diminished the granulomatous inflammatory response of mice to parasite eggs in the liver. The mode of action of CsA is not understood but evidence is presented that supports the proposition that the antiparasite effects are perhaps host-mediated.
 ...
PMID:Prophylactic and therapeutic effects of ciclosporin A in murine Schistosomiasis mansoni: studies on bisexual and unisexual infections and the hepatic inflammatory response. 312 98

The influence of genetic factors on the modulation of hepatosplenomegaly, portal venous pressure and granuloma size in chronic murine schistosomiasis mansoni was studied. Experiments with congenic mice confirmed previous observations that after 8 weeks of infection these disease manifestations are influenced by non-H-2 genes. During chronic infection (20 weeks compared to 8 weeks of infection), hepatosplenomegaly was minimally altered. Portal venous pressure was found to increase in 129/J and BALB/cJ mice, did not change in C57BL/6J and DBA/2J and decreased in CBA/CaJ mice. Simultaneous measurements of granuloma size delineated two groups: decrease of greater than 40%--C57BL/6J, DBA/2J and CBA/CaJ strains and decrease of less than or equal to 20%--129/J, BALB/cJ and C3H/HeJ mice. There was no consistent correlation between the magnitude or direction of alterations in portal pressure and granuloma size among the various strains studied. Furthermore, these alterations were independent of changes in parasite burden (adult worms or hepatic eggs). This amelioration of disease (modulation) was found to be influenced by a small number of non-H-2 genes.
 ...
PMID:Further studies on genetic variation of hepatosplenic disease and modulation in murine schistosomiasis mansoni. 401 Dec 97

Of 7 hybridomas which secrete immunoglobulins binding to crude extracts of Schistosoma japonicum adult worms and/or eggs in solid-phase radioimmunoassays (RIAs), 3 gave positive precipitation reactions in the circumoval precipitin test (COPT). The COPT is a simple and inexpensive immunodiagnostic test for schistosomiasis japonica which involves the incubation of a selected batch of S. japonicum eggs with sera from patients and examination for precipitates one or more days later. Using a competitive RIA with an egg antigen extract and a labelled COPT-positive hybridoma ascites fluid, PwF.41-1-3, the surprising observation was made that only one anti-egg antibody specificity appeared to be represented in the series of 3 antibodies (as ascites fluids). Using sera as inhibitors in the competitive RIA, inhibitory activity (presumably antibodies to the target antigenic determinant of PwF.41-1-3) was readily detected in sera from egg-immunized mice and was of relatively high titre in a strain of mouse (C57BL/6) which can be readily sensitized for large granuloma formation around entrapped eggs in the lungs. Negligible inhibitory activity was found in the sera from S. japonicum-infected patients, even with sera from patients with prominent hepatosplenomegaly. The availability of COPT-positive hybridoma antibodies should facilitate isolation of at least one S. japonicum egg antigen involved in COP reactions and perhaps induction of immunopathological immune responses at least in mice.
 ...
PMID:Murine hybridoma-derived antibodies producing circumoval precipitation (COP) reactions with eggs of Schistosoma japonicum. 719 17

Plasmodium yoelii and Schistosoma mansoni co-infections were studied in female BALB/c mice aged 4-6 weeks to determine the effect of time and stage of concomitant infections on malaria disease outcome. Patent S. mansoni infection in BALB/c mice increased malaria peak parasitemia and caused death from an otherwise non-lethal, self-resolving P. yoelii malaria infection. Exacerbation of malaria parasitemia occurred during both pre-patent and patent S. mansoni infection resulting in a delay of 4-8 days in malaria parasite resolution in co-infected mice. Praziquantel administered to mice with patent schistosome infection protected from fatal outcome during co-infection. However, this treatment did not completely clear the worm infestation, nor did it reduce the peak malaria parasitemia reached, which was nonetheless resolved completely. Hepatosplenomegaly was more marked in schistosome and malaria co-infected mice compared to either infection separately. The results suggest a complex relationship between schistosome co-infection and malaria disease outcome in which the timing of malaria infection in relation to schistosome acquisition is critical to disease outcome and pathology.
 ...
PMID:Plasmodium yoelii: adverse outcome of non-lethal P. yoelii malaria during co-infection with Schistosoma mansoni in BALB/c mouse model. 1936 21

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.
...
PMID:Anthelmintic activity in vivo of epiisopiloturine against juvenile and adult worms of Schistosoma mansoni. 2581 29

Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection. However, HIV infections are highly prevalent in helminth endemic areas. Helminth infections induce polarised Th2 responses that may impair HIV vaccine-generated Th1 responses. In this study, we tested if Schistosoma mansoni (Sm) infection altered immune responses to SAAVI candidate HIV vaccines (DNA and MVA) and an HIV-1 gp140 Env protein vaccine (gp140) and whether parasite elimination by chemotherapy or the presence of Sm eggs (SmE) in the absence of active infection influenced the immunogenicity of these vaccines. In addition, we evaluated helminth-associated pathology in DNA and MVA vaccination groups. Mice were chronically infected with Sm and vaccinated with DNA+MVA in a prime+boost combination or MVA+gp140 in concurrent combination regimens. Some Sm-infected mice were treated with praziquantel (PZQ) prior to vaccinations. Other mice were inoculated with SmE before receiving vaccinations. Unvaccinated mice without Sm infection or SmE inoculation served as controls. HIV responses were evaluated in the blood and spleen while Sm-associated pathology was evaluated in the livers. Sm-infected mice had significantly lower magnitudes of HIV-specific cellular responses after vaccination with DNA+MVA or MVA+gp140 compared to uninfected control mice. Similarly, gp140 Env-specific antibody responses were significantly lower in vaccinated Sm-infected mice compared to controls. Treatment with PZQ partially restored cellular but not humoral immune responses in vaccinated Sm-infected mice. Gp140 Env-specific antibody responses were attenuated in mice that were inoculated with SmE compared to controls. Lastly, Sm-infected mice that were vaccinated with DNA+MVA displayed exacerbated liver pathology as indicated by larger granulomas and increased hepatosplenomegaly when compared with unvaccinated Sm-infected mice. This study shows that chronic schistosomiasis attenuates both HIV-specific T-cell and antibody responses and parasite elimination by chemotherapy may partially restore cellular but not antibody immunity, with additional data suggesting that the presence of SmE retained in the tissues after antihelminthic therapy contributes to lack of full immune restoration. Our data further suggest that helminthiasis may compromise HIV vaccine safety. Overall, these findings suggested a potential negative impact on future HIV vaccinations by helminthiasis in endemic areas.
 ...
PMID:Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model. 3004 50