effect of chronic exposure to organophosphorous insecticides on apoptosis in patients with liver diseases

The rapidly increasing use of organophosphorous compounds in everyday life obligate that greater attention should be paid to the toxic effect exerted by these compounds of human organism. To investigate the effect of chronic exposure to organophosphorous insecticides on liver at chronic hepatitis C virus infection and the chance of development to hepatocellular carcinoma, through studying apoptosis by the measurements of soluble Fas. This study was carried out on sixty subjects; they were divided into six groups: The first control group composed of 10 healthy subjects. The second group composed of ten patients with hepatocellular carcinoma associated with chronic hepatitis C virus and chronic exposure to organophosphorous. The third group composed of ten patients with hepatocellular carcinoma associated with chronic hepatitis C virus. The fourth group composed of ten patients with chronic hepatitis C virus and chronic exposure to organophosphorous. The fifth group composed of ten patients with chronic hepatitis C virus. The sixth group composed of ten patients with chronic exposure to organophosphorous. The time of exposure to organophosphorous was chosen to be over than 10 years. For all groups we do the following investigation: Detection of anti-HCV and HbsAg by ELISA technique, quantitative determination of HCV RNA by real time PCR, estimation of serum levels of bilirubin; albumin level and serum activities of aspartate and alanine aminotransferase; gamma glutamyl transferase activity [GOT]; and prothrombin time, determination of paraoxonase [PON] activity, and determination of sFas by ELISA. All patients show hyperactivity of AST, ALT, and GOT, hypoactivity of PON and high level of sFas. Chronic exposures to organophosphorous giving a high chance to the development of hepatocellular carcinoma by decreasing apoptosis and this risk is further exaggerated by the presence of previous chronic hepatic inflammation as chronic HCV

Role of Helicobacter pylori in refractory iron deficiency anaemia

The role of Helicobacter pylori [H. pylori] infection in the development of iron deficiency anaemia has been the focus of attention during the last decade. Confirmation of the relationship between H. pylori infections and iron deficiency anaemia has not confirmed the pathophysiologic mechanisms involved in this phenomenon was to study the levels of fasting gastric acidity [free and total] as well as the level of tumor necrosis factor alpha in refractory iron deficiency anaemic male patients seropositive for H. pylori infection versus those with seronegativity for H. pylori infection. Also, we tried to find the underlying pathophysiologic mechanism for iron deficiency anaemia observed in these patients. This study was conducted on 30 adult male patients having iron deficiency anaemia and gastroduodenitis. They were subdivided into 2 groups of matched age and haemoglobin value. Group I was seropositive for H. pylori infection and refractory to iron therapy. These patients did not receive prior treatment for eradication of H. pylori infection while group II was seronegative for H. pylori infection and was considered a control group. Patients with active bleeding or previous medical problem were excluded from the study. All patients and controls in the present study were subjected to the following at presentation: careful history taking and thorough clinical examination, complete blood picture, reticulocytes%, assessment of serum iron, total iron binding capacity, serum ferritin, IgG antihelicobacter antibody and tumor necrosis factor-alpha [TNF-alpha], stool for occult blood and measurement of gastric acidity [total and free] by chemical method. Upper endoscopy was done and multiple biopsies were taken and tested for expression of cytotoxin associated gene A [cag A] by polymerase chain reaction [PCR]. results revealed statistically significant higher values of free and total gastric acidity as well as tumor necrosis factor-alpha levels in H. pylori seropositive compared with H. pylori seronegative group. Among H. pylori seropositive group, higher value of TNF-alpha level was observed in H. pylori cagA positive [7 patients] than cagA negative patients [8 patients]. Also, haemoglobin values were inversely correlated with tumor necrosis factor-alpha levels. From this study, we can conclude that elevated serum tumor necrosis factor [TNF-alpha] in H. pylori seropositive group may be one of the underlying pathophysiologic mechanism for iron deficiency anaemia observed in these patients

Involvement of caspase-3, iron regulatory protein-1 and nitric oxide synthase in antimetabolite chemotherapy mediated response in nitric oxide sensitive versus resistant malignancies

Nitric oxide [NO] could be pro or anti-apoptotic depending on cell type and caspase-3 activity. We aimed at studying the effect of antimetabolite chemotherapy on the enzymatic activity of nitric oxide synthase [NOS], caspase-3 and iron regulatory protein-1 [IRP-1] in 20 newly diagnosed acute myeloid leukemia [AML] patients and 10 hepatitis C virus infected hepatocellular carcinoma [HCC] patients since they have varied sensitivity to NO. AML patients received 7+3 regimen [combination of cytosine arabinoside [ara-C] and doxorubicin [DOX] and HCC patients received 5-fluorouracil [5-FU] 500 mg/m2 for 5 days every 3 weeks. All patients were followed up for 6 months to assess their response to therapy. The effect of adding S-nitroso-N-acetyl-penicillamine [SNAP], an NO donor, to chemotherapy on malignant cell survival of mononuclear cells [MNC] from AML patients [NO sensitive] and hepatocytes [NO resistant] from HCC patients was studied in vitro. Ten AML patients in remission and 10 patients having chronic hepatitis C [CHC] of matched age and sex served as controls for AML and HCC patients respectively. Results showed a significant decrease in plasma NOS activity in AML than HCC cases. Also, the MNC and hepatocytes were significantly different in cell aconitase activity, iron content and caspase-3 activity. Significantly higher NOS activity at diagnosis in chemosensitive AML patients compared to chemoresistant patients was also shown. Better chemotherapy response has been associated with significant decline in plasma NOS. MNC aconitase activity and iron content and rise of cellular caspase-3 activity compared to their levels at diagnosis. The HCC cells had significantly higher cellular iron content than chronic hepatitis-C infected cells. The former cells were resistant to 5-FU in vivo and in vitro. In vitro 6-h incubation of MNC with ara-C/ DOX/SNAP -combination was associated with lower percent cell surival, higher caspase-3 activity than cells incubated with ara-C or SNAP/ara-C. Conversely, HCC was insignificantly affected by incubation with 5-FU alone or with SNAP. The cytosolic aconitase activity was significantly inhibited in MNC and HCC following incubation with SNAP alone or with chemotherapy compared to corresponding cells in medium. A decline in intracellular iron was a feature that accompanied sensitivity to chemotherapy in AML cells in vivo and in vitro. This denotes that the interplay between NO level, caspase-3 activity and IRP-1 level largely determines antimetabolite chemosensitivity in different cells. NO donor may have a role in increasing chemosensitivity in AML while its value appears limited in HCC

association between helicobacter pylori cytotoxin associated gene A, vacuolating cytotoxin antigen, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cancer patients

This work aimed at studying the frequency of H. pylori in various solid tumors and hematological malignancies. Also, the association between H. pylori virulence markers [cytotoxin associated gene A, cagA and vacuolating cytotoxin antigen, vacA gene] expression and the plasma level of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 [TIMP-1] in advanced cancer patients was investigated. This study included 17 patients with solid tumors including 8 patients with gastric patients having H. pylori -ve gastric ulcer [served as controls]. All patients and controls complained of dyspepsia. Multiple gastric biopsy specimens from antral and body regions were taken from all cases and controls and tested by polymerase chain reaction [PCR] for the expression of cagA and vacA genes. Plasma MMP-9 and TIMP-1 were measured using ELISA technique. The frequency of H. pylori in this study was 50%, 44.44% and 6 1.54% in gastric cancer, solid tumors and hematological malignancies, respectively. Significant increase in plasma MMP-9 level was detected in solid tumors and hematological malignancies compared to controls. Plasma MMP-9 level was also significantly higher in H. pylori +ve than H. pylori -ve cases with significantly higher values in those expressing cagA than those expressing vacA gene. The highest MMP-9 was present among H. pylori +ve patients with gastroduodenitis. It was concluded that the presence of H. pylori virulence markers especially cagA gene may play a role in cancer progression in cancer patients. So, its early detection and eradication may be beneficial in these patients

Comparative study of nitric oxide and tumor necrosis factor in chronic liver diseases and septicaemic patients

Recent studies point to the potential importance of nitric oxide [NO] in the modulation of sinusoidal blood flow and in the pathogenesis of portal hypertension [PH] So, the aim of the work is to compare the serum level of NO and tumor necrosis factor [TNF] in patients with chronic liver disease [bilharzial hepatic fibrosis [BHF] and liver cirrhosis],normal control and septicaemic, patients. Septicaemic patients were considered as a reference value since they had the highest value of endotoxaemia. This study included 39 patients subdivided into 3 groups. Group I, included 9 patients with BHF, group II, included included 10 immunocompromised patients with septicaemia. In addition, 10 healthy controls of matched age and sex were also included and considered a control group. All patients and controls in this study were subjected to thorough history taking, clinical examination, complete blood picture, hepatic and renal function tests, abdominal ultrasound, TNF [assay by ELISA and NO assay indirectly by assessment of its stable degradation products nitrite and nitrate. The levels of NO and TNF [were statistically significantly elevated in septicaemic patients when compared with their levels in patients having BHF, liver cirrhosis and normal controls. NO had a protective rather than damaging effect on the liver. Care had to be paid with the use of drugs that cause intestinal decontamination and eventually decrease endotoxaemia and prevent the induction of vascular NO synthase