Predicting response to antiviral therapy in patients with chronic hepatitis C

It is unclear whether the combined interferon-ribavirin treatment of chronic hepatitis C [CHC] results in complete elimination of the virus or whether small quantities of virus persist. Early identification of non responders is desirable, because treatment might be terminated to avoid the expense and inconvenience of unnecessary therapy. Evaluation of serum level of hepatitis C virus [HCV] RNA does not always correctly reflect the actual response to antiviral therapy. Analysis of peripheral blood mononuclear cells [PBMCs] for detection of viral RNA should provide more accurate prognostic information. The aim of this study was to investigate the predictive value of clearance of HCV-RNA in serum and PBMCs of patients with CHC after combined Interferon-Ribavirin treatment. Twenty patients with CHC were treated with pegylated Interferon, alfa-2b plus Ribavirin for 6 months. Viral dynamics were assessed by measurement HCV RNA loads in serum and PBMCs at one and six months of therapy by using "real time PCR". Viral load was also measured in liver biopsy of four selected cases at the end of treatment. The complete responders with clearance of HCV RNA in serum and PBMCs at the end of treatment were followed up 6 months after treatment. Early virologic response [EVR]; clearance of serum HCV RNA and normalization of alanine aminotransferase [ALT] at the first month of treatment occurred in 12/20 patients [60%] and persisted to the end of treatment, but six of them [30%] showed positive HCV-RNA in PBMCs. The clearance of HCV RNA from PBMCs at one month of treatment had a negative predictive value of 100%, a positive predictive value of 57.1%, with a sensitivity of 100%, specificity of 50% and accuracy of 70%. After six months of antiviral therapy; clearance of serum HCV RNA was increased to 13/20 [65%], four of them had HCV RNA positive in PBMCs. So, the end of treatment response was achieved in 9/20 [45%]. Negative results of a PBMCs HCV RNA test at the end of treatment had a negative predictive value of 100%, a positive predictive value of 63.6%, with a sensitivity of 100%, specificity of 69.2% and accuracy of 80%. The results of liver biopsy were consistent with that of PBMCs at the end of treatment where two cases showed clearance of HCV RNA from both hepatocytes and PBMCs; while in the other 2 cases, the HCV RNA was detectable in PBMCs and liver biopsy samples. After 6 months follow up; sustained virologic response [SVR] was observed in 7/20 [35%] of the total group. Only 2/20 [10%] showed viral relapse in PBMCs. Conclusion: HCV may persist and replicate in the hepatocytes and PBMCs of serum HCV-RNA negative patients who have persistently normal ALT levels. These patients should be followed up, because they have an ongoing viral infection. The duration of treatment may be tailored according to the early clearance of HCV RNA in both serum and PBMCs at one month of treatment

Evaluation of different methods for detection of helicobacter pylori infection in dyspeptic patients

Helicobacter pylori [H. pylori] is recognized as the major cause of gastritis and peptic ulcer disease and has been classified as a carcinogen class I. Various tests have been developed to diagnose the infection, but all have limitations. H.pylori can be detected by non-invasive and invasive methods, the latter requiring endoscopy. Noninvasive testing for H.pylori is widely available and has been considered as an initial management strategy for uninvestigated dyspepsia. The aim of the present study was the evaluation of the different techniques used for diagnosis of the organism and to compare these techniques to the traditional ones. The present study was carried out on 40 patients suffering from dyspepsia. From these patients gastric biopsy specimens were taken for detection of H.pylori infection by the conventional methods [H and E staining, rapid urease test "RUT", and culture] and the PCR assay. In addition, stool samples were taken for the detection of H.pylori antigen and DNA by ELISA and PCR techniques respectively, saliva samples for PCR and blood samples for detection of H.pylori antibodies IgG were also taken. A case was considered positive for H.pylori infection if the organism was isolated by the culture or at least two of the conventional methods were positive. H.pylori infection was detected in 30 cases [75%]. H.pylori stool assay [HpSA] gave the highest rate of detection [70%], followed by serum antibody detection [50%]. The lowest rate of detection of H.pylori infection was by PCR assay in the stool and the saliva, which detected only 52.5% and 25% of cases respectively. H.pylori in the stool assay [HpSA] could be used as a routine diagnostic tool for H.pylori infection. It seems to overcome some limitations of the conventional invasive techniques. It has the potential advantages of being simple to perform, relatively cheap, and samples can be submitted directly from primary care

Effects of intestinal protozoa infection on gastrointestinal transit and contractility in experimental Animals

Three groups of animals, each was orally infected with Cryptosporidium parvum oocysts, Enterocytozoon bieneusi spores or Cyclospora cayetanensis oocysts, were included in this study. At the time peak of colonization of infected animals, each group and its corresponding control were infused orally with radioactive isotope. Gastric emptying of isotope was significantly greater in infected compared with the controls in both fasted and fed states to determine the effect of each parasite on the contractility of longitudinal and circular muscle. Isometric tension of jejunal segments was recorded. The development of active tension with stretch and the dose-response curve were significantly increased in the longitudinal muscle of the infected animals compared with the controls. The circular smooth muscle did not show an increase in contractility. The results suggested that an altered gastrointestinal transit and smooth muscle contractility may be involved in the intestinal protozoa infections pathophysiology

Central versus peripheral actions of adrenomedullin in a hypertensive rat model

Adrenomedullin [AM] is a peptide with potent vasorelaxing and natriuretic properties originally isolated from human pheochromocytoma. It may function as a circulating hormone that is involved in the regulation of cardiovascular system, renal function and hormone secretion. It has been observed that the hypotensive effect of AM in the periphery is not matched by a similar effect when injected centrally. The mechanisms involved in the peripheral hypotensive and central hypertensive actions of AM in normal rats are controversial and diverse; moreover in hypertension the underlying mechanisms are not tackled till now. 120 male albino rats were used in this study to assess the mechanisms involved in the peripheral versus the central actions of AM in the rat model. Hypertension was induced in 90 rats using NG-nitro-L-arginine ester [L-NAME] and ten normal rats were used as a control group. The peripheral and central actions of AM were tested in the hypertensive rats and in another 20 normal rats. The 90 hypertensive rats were divided into nine equal groups. Peripherally, AM was either injected alone [group I-A] or following a two-weeks of oral administration of prazosin [0.55 mg/kg/day], propranolol [14.4 mg/kg/day], valsartan [14.4 mg/kg/day] or isosorbide dinitrate [10.4 mg/kg/day] [groups II-A to V-A respectively]. Centrally, AM was either injected intracerebroventricularly [icv] alone [group I-B] or following a bolus icv injection of saralain [10 micro g] [group II-B] or after a two-weeks of oral administration of prazosin [0.55 mg/kg/day] or clonidine [18 micro g/kg/day] [group III-B and IV-B respectively]. Mean arterial blood pressure [MABP], plasma renin activity [PRA] and aldosterone level values were compared before and after AM injection in the same rate of each group. A 40.6% drop in MABP was elicited in normal rats injected peripherally with AM. This drop was attenuated to 18.6% in L-NAME hypertensive rats. The percent age drop in MABP in hypertensive rats pretreated with isosorbide dinitrate [43.3%] was comparable to that observed in normal rats when AM was injected intravenously to both groups [p=0.999]. A significant decrease in PRA and aldosterone level was produced in hypertensive rats pretreated with various drugs following the peripheral administration of AM as compared to their pre-injection values. On the other hand, a significant further increase in MABP was obtained following the icv injection of AM to L-NAME hypertensive rats pretreated with saralazin [P=0.000]. The changes observed in MABP, PRA and aldosterone level after the central administration of AM to hyptertensive rats pretreated with either clonidine or prazosin were insignificant as compared to their pre-injection values. This study suggests that the peripheral vasodilator effect of AM is mediated partially via nitric oxide release or probably by other mechanisms. The central hypertensive response to AM in the L-NAME rat model is probably not mediated by angiotensin-II receptors. It could be through enhancing the central sympathetic discharge via an action on either alpha 1, alpha 2 or the suggested imidazoline receptors located centrally. Finally, AM is supposed to be involved in the physiological resetting of renin-angiotensin-aldosterone system possibly secondary to changes in either catecholamines discharge or nitric oxide level. These results were discussed

Effect of cholecystectomy on sphincter of oddi motility in dogs

Gallbladder and sphincter of Oddi [SO] function are controlled by a balance of both hormonal and neuronal factors. Neuronal connections pass between the gallbladder and the SO via the cystic duct. It is therefore possible that cholecystectomy may alter SO motility. The present study investigated the effect of cholecystectomy on SO function in anesthetized dogs. Biliary manometry was performed in a group of anesthetized dogs undergoing cholecystectomy and compared with a control group of matched weight and sex. The cholecystectomized dogs compared with the controls showed a significant increase in mean common bile duct [CBD] pressure together with a significant decrease in mean basal SO pressure and SO phasic frequency. There was also a significant increase in the duration of phasic contractions in the cholecystectomy group compared with the control group. No significant change was noticed in the amplitude of phasic contractions and in the duodenal pressure when comparing both groups. These findings show that the gallbladder serves as a reservoir dampening increases in common duct pressure. The increase in intraductal tension following cholecystectomy in the canine model could overcome the choledochoduodenal sphincter resistance resulting in a drop in SO basal pressure associated with a decrease in the frequency of phasic contractions. It is also possible that ductal distension inhibits SO function by local reflexes. Removal of the gallbladder itself may eliminate a significant component of the neural circuity modulating biliary function. Such effects may ultimately lead to the SO manometric abnormalities, which have been described for SO dysfunction