Food additives and Hymenolepis nana infection: an experimental study

The effect of sodium benzoate [SB] on the pathogenesis of Hymenolepis nana [H. nana] and its neurological manifestations was studied in the present work. One hundred and thirty five mice were classified into three groups. GI: received SB alone, GII: received SB before and after infection with H. nana and GIII: infected with H. nana. All groups were subjected to parasitological, histopathological, immunohistochemical and biochemical assays. The results revealed a significant decrease in TL-4 serum level with a significant increase in gamma amino butyric acid [GABA] and decrease in zinc brain levels in GI, while GII showed non significant increase in IL-4 level that resulted in a highly significant increase in the mean number of cysticercoids and adult worms with delayed expulsion as compared to GIII. This was reflected on histopathological and immunohistochemical changes in the brain. Also, there was a highly significant increase in GABA and decrease in zinc brain levels in GII to the degree that induced behavioral changes. This emphasizes the possible synergistic effect of SB on the neurological manifestations of H. nana and could, in part, explain the increased incidence of behavioral changes in children exposed to high doses of SB and unfortunately have H. nana infection

Genetic polymorphism of glutathione-S- transferase [GST-M1 and GST-T1] in schistosomiasis -associated bladder cancer in Egyptian patients

This work was carried out on three groups, 30 Egyptian patients with Schistosoma haematobium [S. haematobium] with bladder cancer [15], and without bladder cancer [15], as well as 15 normal individuals as a control. All the individuals were subjected to measurement of serum level of GST by using ELISA technique and genotyping for GST-M1 and GST-T1 using PCR technique. The results proved that GST serum level was significantly deceased in S. haematobium patients with bladder cancer as compared to the other groups. The PCR results for the GST-M1 and GST-T1 genotyping showed 4 categories, [M1+ve/T1+ve, M1+ve/T1-ve, M1-ve/T1+ve, M1-ve/T1/-ve]. There was a significant decrease in enzyme levels in patients with GST-M1-ve/T1-ve as compared to the other categories. Besides, there was a significant increased risk for bladder cancer development in patients with combined gene deletion [OR = 40] which represented mainly in S. haematobium patients with bladder cancer [53.3% = M1-ve/T1-ve]

Immunohistochemical and neurotransmitter changes in the brain of mice infected with hymenolepis nana

Hymenolepis nana is one of opportunistic parasites which is widely distributed specially amongst children and immunosuppressed patients. Some neurological manifestations can occur in immunosupressed hosts, however, their possible pathogenesis is not clearly yet idenified. The aim of the present work is to study the possible pathogenesis of the neurological manifestations in Hymenolepis nana infection. Swiss albino mice were used in this study which was divided into two groups. Group I: Mice were maintained immunocompetent [IC]. Group II: Mice were immunosupressed [IS] by subcutaneous injection of cortisone. Mice of both groups were orally infected with H.nana eggs. Mice were sacrificed at different durations post infecion [p.i.]. Small intestine, liver and brain of each sacrificed mouse were removed. Couning of cysticercoids and adult worms in small intestine was performed. Livers were examined histopathologically for the possible cysticercoid disseminalion. Brains were processed for histopathological examination and immunohistochemical examinalion for the possible antigenic deposition by PAP technique. In addition the brain tissue was processed for biochemical estimation of the levels of some neurotransmitters as: Gamma-aminobutyric acid [GABA], norepinephfine [NE] and serotonin [5-HT] as well as zinc as one of trace elements. The results of the present study showed a significant increase in the number of cysicercoids and adult worms with delayed expulsion in immunosupressed [IS] mice with manifest histopathological changes in small intestinal mucosa. Aberrant cysticercoids were detected in the liver of IS mice. Regarding the brain examination, there were marked histopathological changes with specific antigenic deposition in IS mice. There were statistical increase in the levels of GABA and NE and staistical decrease in the levels of 5-HT and zinc in brains of IS mice examined at 3 and 5 months p.i. On the basis of the results of the present study, it has been shown that in case of immunosuppression, Hymenolepis nana infection can affect the brain as evidenced by the marked histopathological changes, specific antigenic deposition and the significant changes in the levels of neurotransmitters and zinc in the brain tissue. Since H. nana is widespread and since increasing numbers of patients are given immunosuppressive treatment, it is possible that this peculiar neurological manifestation of H.nana infection is occurring but not being diagnosed. The pathogenesis of such manifestations seemed to be dependent on multifactors that acting together and affecting each other

Metallothionein [MTI and MT II] gene expression in hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is one of the most frequent human tumors worldwide, and commonly evolves from chronic hepatitis and liver cirrhosis. It is therefore very important to detect and evaluate the progressing state of chronic hepatic disorders. Recently, serum metal levels such as copper [Cu] and zinc [Zn] have been reported to be highly sensitive in the diagnosis of some diseases. Hypozincemia and marked hypercupremia have been reported in patients with digestive, hepatic, breast, and lung cancers. Also much attention was paid to the association between metallothioneins [MTs] and chronic liver diseases including HCC. Available informations suggested that MTs might play important roles in carcinogenic and apoptotic process of some tumors. The aim of the present study was to throw the light on the role of zinc, copper and metallothioneine in the diagnosis of chronic liver diseases and to clarify the role of metallothioneins [MTs] I and II mRNA expression in hepatocellular carcinoma. This study was carried out on 45 patients with liver diseases [15 patients with chronic hepatitis, 15 patients with liver cirrhosis and 15 patients with HCC] as well as 15 healthy individuals as a control group. All patients and controls were subjected to estimation of serum copper, zinc and metallothioneine levels also their tissue levels were estimated in all patient groups. Metallothioneins [MT I and MT II] mRNA expression by RT-PCR were done for all cases. The results of the present study documented a significant decrease in serum and tissue levels of zinc and metallothioneine with concomitant increase in copper levels in all patient groups. More changes were documented in HCC patients. Concerning the PCR results of MT genes expression, there was a significant decrease in MT I and MT II mRNA expression in HCC patients when compared to the other groups. They also decreased in patients with liver cirrhosis when compared to the control group and patients with chronic hepatitis. In contrast their expressions do not show significant decrease in chronic hepatitis when compared to the control group. On the basis of these results, it could be concluded that serum zinc, copper, and metallothioneines levels may be used as a non-invasive biochemical markers for early detection of the progression of chronic liver diseases. Moreover, the progressive decrease in MT I and MT II gene expression may play an important role in carcinogenesis of HCC

Genetic polymorphism of glutathione-s-transferase [GST-M1 and GST-T1] in Egyptian schistosomiasis -associated bladder cancer

Bladder cancer is a common neoplasm around the world. In Egypt, the majority of bladder cancer is associated with Schistosoma haematobium [S. haematobium]. Glutathione-s-transferase [GST] represents an important family of metabolizing enzymes that catalyzes the conjugation of large variety of endogenous and exogenous compounds including carcinogens and anti cancer drugs and their metabolites with reduced glutathione. Individuals with very low levels of GSTs are at increased risk for the development of carcinoma and inflammatory diseases. The potential role of GST gene polymorphism on bladder cancer susceptibility is less certain. So, the aim of this work was to study GST-M1 and GST-T1 genes polymorphism in Egyptian patients with S. haematobium to clarify its role on bladder cancer susceptibility in those patients. This was carried out on three groups, 15 Egyptian patients with S. haematobium with bladder cancer, 15 Egyptian patients with S. haematobium without bladder cancer and 10 normal individual as a control group. All individuals were subjected to measurement of serum level of GST using ELISA technique and genotyping for GST-M1 and GST-T1 using PCR technique. The results proved that GST serum level in Schistosoma patients without bladder cancer was decreased but not statistically significant if compared to control group, in contrast it was significantly deceased in Schistosoma patients with bladder cancer if compared to the other groups. PCR results for GST-M1 and GST-T1 genotyping had shown 4 categories, in control group [M1+ve/T1+ve [80%], M1+ve/T1-ve[10%], M1-ve/T1+ve[10%], M1-ve/T1/-ve[0%]], in Schistosoma without bladder cancer [M1+ve/T1+ve[66.7%], M1+ve /T1-ve[13.3%], M1-ve/T1+ve[13.3%], M1 -ve/T1-ve[6.7%]], while in Schistosoma patients with bladder cancer [M1+ve/T1+ve[13.3%], M1+ve/T1-ve[13.3%], M1-ve/T1+ve[20%] and M1-ve/T1-ve [53.3%]]. It was demonstrated a significant decrease in enzyme levels in patients with homozygous deletions of both GST-M1 and GST-T1 genes [GST-M1-ve/T1-ve] if compared to the other three categories of genotyping. Moreover, there was a significant increased risk for development of bladder cancer in patients with combined gene deletion [OR=40] which represented mainly in Schistosoma patients with bladder cancer [53.3% were M1-ve/T1-ve]. Bladder cancer is a common multifactorial disease, and genetic polymorphism especially in GST-M1 and GST-T1 could play an important role as a risk factors in development of urinary bladder cancer among Egyptian with Schistosoma haematobium. So, it could be used for early prediction of risk group in order to help them by follow up for early diagnosis or by cancer chemoprotection

impact of subchronic mercury exposure on the immune response and pathogenesis of experimental cryptosporidiosis

Mercury is one of the most widely distributed heavy metal which incriminated in the environmental pollution. Evidence is emerging that chronic exposure to mercury may elicit immunomodulation with enhanced host susceptibility to bacterial, viral and parasitic infection. Therefore a special attention is payed in this study to test the impact of subchronic mercury exposure on the immune response and the pathogenesis of experimental cryptosporidiosis. One hundred and sixty, parasite free, albino mice were used in this study and were divided Into four groups:-Group [1]: consisted of 50 mice which received an oral daily dose of mercury for 28 days before infection with Cryptosporidium oocysts. Group [2]: consisted of 50 mice which infected with Cryptosporidium oocysts without mercury treatment, Group, [3]: consisted of 50 mice, which received mercury treatment only and Group [4]: consisted of 1.0 mice with no infection and no mercury treatment [control group]. The influence of the subchronic mercury exposure on the pathogenesis of cryptosporidiosis will be assessed by counting the fecal oocysts, histopathological examination of different organs of infected mice and biochemical estimation of the glycogen and protein contents in both liver and heart tissues at early stage of infection, Lastly, the levels of IFN-gamma and IL10 in the sera will be measured during the course of experiment. The results of the present work showed that group [1] had shorter prepatent period as fecal oocysts could be detected from first day post infection, remained infected longer and shed more oocysts with higher mortality rate as compared to group [2]. In addition, a significantly higher number of endogenous stages were detected in group [1] with severe villous atrophy and heavy infestation with the endogenous stages than in group [2]. Regarding the levels of glycogen and protein, groups [1and 2] showed statistically significant decrease in the level of glycogen in liver and heart tissues whereas, the level of protein increased in the liver unlike the cardiomyocyte that showed marked protein decrease as compared to other groups. Moreover, there was a statistical significant increase in the levels IFN-gamma and IL10 in group [2] as compared the lower levels detected in group [1], Therefore, the result of the present work strongly support the immunosuppressive effect of mercury on experimental cryptosporidiosis as evident.by flaring up of the intestinal infection with the extraintestinal spread of the parasite as well as the induction of functional impairment in liver and heart tissues. Therefore, these results would spotlight on the wide spread environmental pollution with mercury which may be incriminated in the flaring up of the opportunistic parasites specially among children and its possible hazardous effect on their health