Effects of adding hypertonic saline solutions and/or etilefrine to standard diuretics therapy in cirrhotic patients with ascites.

OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) activation is the milestone in ascites formation. Hypertonic saline solution (HSS) has attracted considerable interest over the last years in ascites control. Other therapeutic models and concepts have been introduced to overcome diuretic resistance and control ascites. We aimed to evaluate the effects of adding HSS infusion and/or etilefrine to oral diuretics therapy on inflammatory and metabolic pathways, renal and systemic hemodynamics, and clinical outcomes by estimating the changes in selected biochemical and biological markers in cirrhotic patients with ascites. PATIENTS AND METHODS: Ninety cirrhotic patients with ascites were studied after administration of HSS infusion (n=25) or etilefrine tablets (n=25), or both (n=25) plus standard diuretics therapy (SDT), or SDT alone (n=15). Serum levels of interleukin-6 (IL-6), aldosterone, leptin, and C-reactive protein (CRP). Hepatic and renal functions were measured at baseline, after eight days, then after 38 days. RESULTS: A significant reduction in serum IL-6, serum aldosterone, Child-Pugh score, MELD-Na score, and increase in serum leptin, and mean arterial pressure (p<0.05) were noted after 38 days in HSS and combination groups. A significant improvement in diuresis, in all groups, urinary sodium excretion, and creatinine clearance (p<0.05) were increased after 38 days in all groups except the SDT group. CONCLUSIONS: The results suggest that HSS, etilefrine, and their combination plus SDT are superior to SDT alone for ascites control and can exert some benefits on clinical, systemic, inflammatory, renal, and metabolic pathways without renal or hepatic dysfunction.

Distinct serum immunoglobulins pattern in Egyptian patients with chronic HCV infection analyzed by nephelometry.

Hepatitis C has emerged as a major worldwide public health problem. The host immune response to HCV infection is composed of both a non-specific immune response, including interferon (IFN) production and natural killer (NK) cell activity, and a virus-specific immune response, including humoral and cellular components. Susceptibility to infection has been related to immunological disturbances. Several studies have provided experimental evidence of disorders of both cellular and humoral immunity. The present study was carried out to evaluate the serum immunoglobulins level (IgG, IgM, IgA) and IgG-subclasses (IgG1-4) in chronic hepatitis C patients in comparison with healthy control patients. This study included 50 patients with biochemical, serologic, virologic, and histologic evidence of chronic hepatitis C. Total IgG, IgA, and IgM were assayed by nephelometry. IgG subclasses were assayed using human IgG subclasses enzyme immunoassay. The results showed a significant increase of total serum IgG and IgM levels found in patients with chronic HCV compared with the healthy control patients (P < 0.001 for each). There was a statistically significant difference in the IgG subclasses (IgG1 to IgG4) between the patients and controls (P < 0.001 for each). On the other hand, no significant difference was found between patients and healthy controls in IgA level (P = 0.4). The normal total serum immunoglobulins pattern is apparently shifted in chronic hepatitis C infection in the Egyptian patients. This pattern may include an ethnic or biologic background and could be used in the differentiation of the patients with minimal liver disease.

Interleukin (IL)-4, IL-10, IL-18 and IFN-gamma cytokines pattern in patients with combined hepatitis C virus and Schistosoma mansoni infections.

Schistosoma mansoni infection is characterized by a strong T-helper type 2 (Th2) cell-associated immune response, but in the case of viral infection, it is associated with interferon-gamma (IFN-gamma) increase and induction of Th1 immune response. Few data are available about the immune response of cases infected with combined hepatitis C virus (HCV) and schistosomiasis. Thus, the investigation of the cytokine pattern in patients coinfected with both HCV and Schistosoma mansoni was our rationale. This study included four patient groups: Group 1 included 20 patients infected with chronic HCV, Group 2 included 15 patients infected with schistosomiasis alone, Group 3 included 20 patients with chronic HCV and schistosomiasis and Group 4 included 15 healthy control individuals with matched age and sex. Serum levels of IFN-gamma, interleukin (IL)-4, IL-10 and IL-18 were measured in all groups by enzyme-linked immunosorbent assay. The results showed that the patients infected with HCV had significantly higher serum levels of IFN-gamma and IL-18 compared with the controls and with the patients with schistosomiasis and coinfection (P < 0.001). On the other hand, serum levels of IL-4 and IL-10 were significantly higher in patients with schistosomiasis and coinfection compared with the control group (P < 0.001 and 0.0001, respectively) and with the HCV patients (P < 0.05 and P < 0.001, respectively). A significant increase in serum levels of IL-4 and IL-10 was also found in HCV patients compared with the control (P < 0.05). Schistosomiasis appears to induce a Th2 cytokine profile, with increase in serum levels of IL-4 and IL-10, even in the presence of HCV coinfection. In conclusion, schistosomiasis may downregulate the stimulatory effect of HCV on Th1 cytokines and this may lead to the chronicity of HCV infection in coinfected patients.

Role of concurrent S. mansoni infection in H. pylori-associated gastritis: a flow cytometric DNA-analysis and oxyradicals correlations.

BACKGROUND/AIM: Helicobacter pylori infection is associated with the development of atrophic gastritis and increased gastric epithelial proliferation that is important in developing gastric carcinoma. Some countries with a high prevalence of H. pylori infection have high gastric cancer rates, whereas in others these rates are low. Several theories have been advanced to explain this phenomenon. One of these explanations is that the concurrent parasitic infection that is common in the African population might alter the immune response to H. pylori infection and reduce the incidence of atrophic gastritis. 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 (NO), oxyradicals and antioxidant capacity status. PATIENTS/METHODS: Between April 2001 and March 2002, 73 patients were subjected to upper gastrointestinal endoscopy for dyspepsia and liver cirrhosis in the National Liver Institute, Menoufiya University. Biopsies were obtained from any lesion as well as from apparently healthy mucosa. Specimens were preserved in RNA later solution, and then kept at -80 degrees C until utilized for estimation of DNA-flow cytometric assay, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), NO and lipid peroxidation (LPO) product--malondialdehyde (MDA). Diagnosis of bilharziasis was done by stool analysis, or by sigmoidoscopy and rectal snip. RESULTS: Of the 73 patients, 48 were H. pylori-positive, 34 of them were positive and 14 were negative for S. mansoni. Of the 25 H. pylori-negative cases, 18 were positive and 7 were negative for S. mansoni. Concurrent infection with S. mansoni occurred in 34 patients and they had reduced DNA S-phase (7.57 +/- 4.99 vs. 14.5 +/- 3.11, P = 0.001), reduced proliferation activity (9.95 +/- 3.95 vs. 16.78, P < 0.004) and reduced apoptosis (21.83 +/- 11.64 vs. 26.0 +/- 8.31, P > 0.05) compared with H. pylori infected patients alone. CONCLUSIONS: The results demonstrate that concurrent helminthes infection may modify the inflammatory response to gastric H. pylori infection manifested by the reduction of oxyradical-induced DNA-damage, apoptosis and cellular proliferation activity, and the increase in antioxidant production. Concurrent S. mansoni infection may have a protective effect against the possible progression of H. pylori-induced gastritis towards gastric carcinoma.

Study of antioxidant enzymes level and phagocytic activity in chronic liver disease patients.

Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. A predictable consequence of cholestasis is malabsorption of fat-soluble vitamins and free radical scavengers. On the other hand, it has been postulated that cholestasis affects polymorphonuclear leukocytes function by impeding chemotaxis, phagocytosis and superoxide anion release in experimental animals. This work is aimed to evaluate the antioxidant status and phagocytic activity of neutrophils in chronic liver disease patients. 15 primary biliary cirrhosis (PBC) patients, 15 primary sclerosing cholangitis (PSC) patients, 15 chronic viral hepatitis C (HCV) patients, and 15 healthy individuals (control group) were included in this study. Levels of catalase (Cat), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and malondialdehyde (MDA) were assessed in both serum and neutrophils homogenates. Neutrophils function was estimated by nitroblue tetrazolium (NBT) reduction assay. A marked decrease in the antioxidant status was observed in serum and neutrophils' homogenate of patients with chronic liver diseases compared to healthy subjects. Significant elevation of lipid peroxides was found in all groups of liver disease patients. The majority of patients had reduced value in NBT reduction assay, which suggested a lack of response to infection by neutrophils. In conclusion, deficient antioxidant defense mechanisms may lead to excess oxygen free radicals formation that promote the pathological process in the liver. The use of free radicals scavengers by chronic liver patients may potentiate the antioxidant defense system against oxidative stress.

A safe, effective, herbal antischistosomal therapy derived from myrrh.

Schistosomiasis is a widespread helminthic disease. Treatment of schistosomiasis is based on chemotherapy with praziquantel, which is the drug of choice. Since resistance to praziquantel has been demonstrated, alternative drugs must be considered. Myrrh is an oleo-gum resin from the stem of the plant Commiphora molmol. This study was carried out on 204 patients with schistosomiasis. The drug was given at a dose of 10 mg/kg of body weight/day for three days, and induced a cure rate of 91.7%. Re-treatment of cases who did not respond with a dose of 10 mg/kg of body weight/day for six days gave a cure rate of 76.5%, increasing the overall cure rate to 98.09%. The drug was well tolerated, and side effects were mild and transient. Twenty cases provided biopsy specimens six months after treatment and none of them showed living ova.

The effect of hydrogen ion on the steady-state multiplicity of substrate-inhibited enzymatic reactions. II. Transient behavior.

In this paper we concentrate our attention on the stability and transient behavior of the isothermal system (CSTR) with a substrate-inhibited enzyme reaction producing hydrogen ions. Our investigation covers the region of multiple steady states uncovered previously (1) (ordinary hysteresis and isola). We investigate the local stability characteristics of the different steady states, the effect of the initial condition on the transient behavior and the response of the system to feed disturbances of various magnitudes and durations.