Immunohistological examination of long term changes of the t-cell mediated immune response in egyptian patients with chronic hepatitis C with and without schistosoma mansoni infection

The host immune response is playing a key role in liver injury occurring in patients with chronic hepatitis C or schistosomiasis or in case of coinfection. The rational of the current study is to investigate the cell mediated immunity in the liver of patients with or without cirrhosis due to hepatitis C or schistosomiasis or both. The CD3 [Tlymphocytes], CD4 [helper/inducer T-cells], CD8 [suppressor/cytotoxic T-cells], CD11b, and CD16 [NK activity] were counted immunohistochemically in liver samples using specific monoclones in four patient groups, non-cirrhotic patients free of schistosomiasis with hepatitis C [Group I], non- cirrhotic patients coinfected with schistosomiasis and hepatitis C [Group II], cirrhotic patients free of schistosomiasis with hepatitis C [Group III], and cirrhotic patients coinfected with both schistosomiasis and hepatitis C [Group IV]. The results showed that there is a significant difference between the four groups of patients regarding CD4 count. Patients without schistosoma coinfection and without cirrhosis [Group I] showed significantly [P < 0.001] risen counts of CD4+ compared to patients with coinfection and cirrhotic remodelling [Group IV]. For patients suffering from liver cirrhosis [Group III] significantly elevated levels of CD4+ lymphocytes [P = 0.014] were detectable compared to patients already suffering from liver cirrhosis and coinfection [Group IV]. The counted CD4 cells in chronic hepatitis C group without S. mansoni infection [group one] was found elevated versus the count of CD4 cells in the group with the coinfection [group two] and this was statistically significant [P = 0.01]. The CD8 count was statistically highly significant between the four groups. CD8 cells count in the two groups with the coinfection was found elevated against the other two groups with HCV infection only. On the other hand, the patients coinfected with schistosome without cirrhosis [Group II] and with cirrhosis [Group IV] showed a significant elevation of CD8 versus patients infected with HCV only without cirrhosis [Group I] [P = 0.001] and [P < 0.0001] respectively. Moreover, the patients coinfected with schistosome with cirrhosis [Group IV] showed a significant elevation of CD8 versus patients infected with HCV only with cirrhosis [Group III] [P = 0.022]. The obtained CD4/8 ratio was decreased in coinfected versus the nonconifected patients. The CD3, CD11b, and CD16 cells counts were non-significantly different among the four groups. Collectively, the schistosome coinfection increases the level of CD8 and decreases the CD4 count in livers of cirrhotic and non-cirrhotic patients. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes cells may play a role in the immunopathogenesis of liver cirrhosis in patients with HCV and severely in coinfected patients with both hepatitis C and schistosomiasis

Protective effect of balanites aegyptia on antioxidant deffense system againt adriamycin-induced cariac toxicity in experimental mice

Samir A. El Masry, Mohamed M. Ebeed, Ibrahim H. El Sayed, Mohamed Y. Nasr and Khalil A. El Halafawy. Protective effect of Balanites aegyptiaca on antioxidant defense system against Adriamycin-induced cardiac toxicity in experimental mice. Adriamycin is an anthracycline antibiotic that is widely used as a chemotherapeutic agent. However, usefulness of this agent is limited due to its cardiotoxic effects. Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin. The rationale of the present study was to evaluate the potential protective effect of Balanites aegyptiaca [B. aegyptiaca] as a source of the natural antioxidants against adriamycin-induced cardiotoxicity in experimental mice. In present study, four groups [ten animals in each group] of experimental mice were used as follows: Group 1, mice not received both Adriamycin drug and B. aegyptiaca extract and served as a negative control group; Group 2, mice received Adriamycin intraperitoneally [2.5 mg/kg BW] in six equal injections over a period of two weeks for a cumulative dose of 15 mg/kg BW; Group 3, mice orally administered with B. aegyptiaca extract [400 mg/kg BW], through an intragastric feeding tube over a period of three weeks; Group 4, mice treated orally with B. aegyptiaca extract plus intraperitoneally adriamycin administration [2.5 mg/kg BW]. Serum Lactate dehydrogenase [LDH], Creatine phosphokinase [CPK], Glutamate oxaloacetate transaminase [GOT], Glutamate pyruvate transaminase [GPT], Lipid peroxide [LPO], total Nitric oxide [NO]. erythrocyte lysate Superoxide dismutase [SOD], Glutathion peroxidase [GPx] and plasma Catalase [CAT] were measured in all tested groups. The results showed that, Adriamycin elevated the activities of LDH, CPK, GOT, GPT, LPO and total NO content in the mice heart tissue. Also, Adriamycin drug reduced the activities of SOD, GPx and CAT. Pretreatment with B. aegyptiaca extract significantly [p<0.05] prevented these alterations and restored the enzyme activities to near normal levels. Application of B. aegyptiaca extract with Adriamycin drug either reduced or completely prevented its toxic effects. So, these findings demonstrate the cardio protective effect of B. aegyptiaca on antioxidant tissue defense system during Adriamycin induced cardiac damage in mice. Therefore it could be recommended for further investigation in this potentially new indication for clinical application

Decreased Helicobacter pylori-associated gastric epithelial proliferation by concurrent Schistosomal infection

Helicobacter pylori [H. pylori] injection is associated with increased gastric epithelial proliferation, the enhanced epithelial proliferation is important in developing gastric carcinoma. Some developing countries with a high prevalence of H. pylori infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by T-helper cell, type 1 [Th1] response may be modulated by concurrent parasitic infection. Pathogenic helminths of the genus Schistosoma cause T-helper cell, type 2 [Th2] response to parasite eggs. The Th2 response is usually associated with down regulation of Th1 cytokine synthesis. The aim of the present study was to assess whether concurrent Schistosoma mansoni infection with H. pylori has an effect on gastric mucosal injury in view of cell proliferation, apoptosis, pathological changes, nitric oxide and oxyradicals status. Between April 2001 and March 2002, 73 patients [13 child and 60 adults] were subjected to upper gastrointestinal endoscopy for dyspepsia and liver cirrhosis in the National Liver Institute, Menoufiya University. Four biopsy specimens were taken, two from the greater curvature of the antrum and two from the upper body of the stomach, biopsies were obtained from any lesion as well as from apparently healthy mucosa. One snap from each site was preserved in RNA later solution, then kept at -80°C till utilized for estimation of DNA-flow cytometric assay, reduced glutathion [GSH], catalase [CAT], superoxide dismutase [SOD], Nitric oxide [NO], and lipid peroxidation product- malondialdehyde [MDA]-. Diagnosis of bilharziasis was done by stool analysis, or by sigmoidoscopy and rectal snip. OF the 73 patients, 60 patients were cirrhotic [20 Child A, 34 B, 6 C], 48 were H. pylori-positive and 25 H. pylori negative. The mean age in H. pylori positive patients [46.31 +/- 10.7 years] was significantly less than in H. pylori - negative patients [52.8 +/- 7.2 years]. Infection with H. pylori alone correlated with increased DNA s-phase, proliferation activity and apoptosis [sub-G phase] [p 0.04, 0.03 and 0.04] respectively. Concurrent infection with schistosomiasis occurred in 34 patients and it significantly suppressed DNA 5-phase [P=0.001], proliferation activity [p<0.004], and apoptosis [sub-G phase], [p>0.05]. On contrast, concurrent infection had an adverse effect on liver cirrhosis with increased incidence of upper gastrointestinal bleeding. Schistosomal concurrent infection with H. pylori is associated with higher incidence of superficial gastritis, and may complicate liver cirrhosis with increased upper gastrointestinal bleeding. On the other hand, concurrent schistosomal infection may have a protective effect against the possible progression of H. pylori induced gastritis towards gastric carcinoma, by modulating the cytokine profile of the gastric mucosa with suppression of the proliferation activity. A detailed study of the cytokine expression in similar cases is recommended for unraveling the mystery of this phenomenon