Study of annexin V in hepatic fibrosis with and without gastrointestinal haemorrhage

Annexins are family of proteins expressed throughout multicelullar eukaryotic phyla but whose functions are poorly understood. Biochemically, annexins are defined as soluble, hydrophilic proteins that bind to negatively charged phospholipids in a Ca[+2]-dependent manner. This binding is reversible, and removal of Ca[+2] by Ca[2+] chelating agents will lead to a libration of annexins from the phospholipid matrix. Certain dysregultion in annexin expression, properties, or localization may contribute to the pathophysiology of disease phenotypes. This has led to the introduction of the term [annexinopathies]. The aim of this work was to study the role of annexin V in hepatic fibrosis with and without gastrointestinal haemorrhage. This study was carried out on sixty patients with hepatic fibrosis [diagnosed by liver biopsy], and were subdivided into two groups: Group I included 30 patients had no history of variceal bleeding, Group II included 30 patients had history of variceal bleeding, and 10 healthy subjects as a control group. Abdominal ultrasound with Doppler assessment of hepatic haemodynamic, upper Gl endoscopic examination, measurement of plasma Annexin V level by enzyme linked immunosorbent assay were done. There was a significant increase of the mean plasma annexin V level in group [I and II] more than in controls, and it was being significantly higher in group II than in group I. There were no statistically significant relation between the plasma annexin V level and the Child-Pugh score, grades of esophageal varices, portal pressure or grades of portal hypertension in group I or in group II

Study of endothelin in portal hypertension

The aim of this study was to evaluate the plasma level of endothelin -1 in portal hypertension in patients with hepatic cirrhosis. Thirty patients with portal hypertension due to cirrhotic liver were studied at the Critical Care Medicine and Internal Medicine departments at Alexandria Main University Hospital. Clinical evaluation of the severity of illness was done using Modified Child- Pugh Score and portal hypertension was assessed by doing Duplex Doppler ultrasonogram. Plasma levels of endothelin-1 [ET-1] were estimated by radioimmunoassay. Plasma levels of endothelin-1 [ET-1] were significantly higher in patients with portal hypertension than control group [mean +/- SD was 94.3 +/- 14.91, 33.8 +/- 5.39 ng/ml respectively, p=.000]. Also, the study showed that plasma levels of ET-1 were significantly higher in patients with ascites than without [mean +/- SD was 104.15 +/- 11.71, 86.77 +/- 12.68 ng/ml respectively, p= .001]. The levels of ET-1 were significantly higher with the increased severity of liver disease according to modified Child -Pugh score [F = 10.25, p = .005]. Plasma ET-1 concentrations were increased in patients with portal hypertension with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increasing of plasma levels of endothelin was related to the severity of liver disease. The result of the present work may be of help in understanding the mechanism and may open a new field in the management of portal hypertension

IL-6 and thyroid hormones in critically ill patients with sepsis

The aim of this study was to investigate whether the activation of the cytokine system, in particular, activation of interleukin-6 production, has a role in pathogenesis of thyroid hormones changes in critically ill patients with sepsis. Thirty one patients with sepsis were studied at the Critical Care Medicine department at Alexandria Main University Hospital. Clinical evaluation of the severity of illness was done using sepsis related organ failure score [SOFA score]. Blood samples were obtained within 6 hours after admission and were collected with EDTA. Plasma was separated by centrifugation at 3000rPM for 10 minutes and stored at -80°C until assayed. 10 blood samples were obtained from healthy volunteers [5 males and 5 females] as control group. These plasma samples were used for measurement of inerleukin-6 [IL-6], free thyroxine [fT4], free triiodothyronine [f T[3]] and thyroid stimulating hormone [TSH]. Serum interleukin-6 level was significantly higher in patients with sepsis than control group [mean +/- SD was 100.904 +/- 10.941 pg/ml versus 26.652 +/- 5.125 pg/ml respectively, P = 0.0001*]. The patients were divided into 4 groups according to SOFA score. It was found that fT3 and FT4 levels were significantly decreased with increased severity of sepsis [F= 20.306, P=.000* and F= 7.025, P= .001* respectively], while serum levels of IL-6 were increased significantly with the increased severity of sepsis [F =18.55, p =.000*]. A significantly positive correlation was found between IL-6 and SOFA score, [r = .823, P .000*] while significantly negative correlation was found between levels of fT3 and serum IL-6 levels and SOFA score, [r= -.887, P = .000* and r = -.866, P= .000* respectively]. Also, a significant negative correlation was found between levels of fT4 and serum IL-6 levels and SOFA score [r= -.597. P =.000* and r= -.579, P = .000* respectively]. Also, there was a negative correlation between TSH, IL-6 and SOFA score levels but significant only with IL-6 levels [r= -0.407, P= .023* and r= -.0085, P= 0.649 respectively.] This study demonstrated that there is a positive correlation between serum level of IL-6 and severity of sepsis as it was significantly increased with increased SOFA score. While fT3, fT4 and TSH levels are significantly decreased with increased levels of IL-6. So, these suggest that the activation of the cytokine system, in particular, activation of interleukin-6 production, has a role in pathogenesis of thyroid hormones changes in critically ill patients with sepsis

Study of the mechanism underlying the prokinetic action of erythromycin on lower esophageal sphincter pressure in dogs

Erythromycin [EM] and a number of its derivatives exhibit prokinetic properties. In particular, the drug increases the contractile activity of smooth muscles of esophagus and promotes gastric emptying in both health and disease. The drug enhances esophageal and gastric motility by acting as a motilin agonist. The aim of the study was to evaluate the effect of low dose of EM, as a prokinetic agent, on the lower esophageal sphincter pressure [LESP] and to study the receptors involved in the mediation of the prokinetic action of EM. The study was carried out on 30 adult healthy dogs [10-15 kg] divided into five groups, each group consisted of 6 dogs. The studied groups were: I: a control group [placebo treated], II: an erythromycin treated group [EM gp] [7 mg/kg b.w. by i.v.i], and three groups III, IV, V that were treated with EM [7 mg/kg b.w. i.v.L preceded by either atropine [a muscarinic blocker] in a dose of 40 micro ag/kg b.w. i.v.i., ondansetrone [5 HT3 antagonist] in a dose of 0.1 mg/kg b.w. i.v.i or metoclopramide [dopamine receptor type 2 antagonist] in a dose of 150 micro g/kg b.w. i.v.i. respectively. After an over night fasting, basal recording of LESP was carried out in each group by an esophageal manometer connected to a pressure transducer. LESP was recorded for all animals in all groups fifteen minutes after the end of the predescribed treatments. Data obtained showed that EM significantly increased the resting LESP. Pretreatment with either atropine or ondansetrone totally prevented the increase in LESP induced by EM. However, pretreatment with metoclopramide failed to prevent the increase in LESP induced by EM. The findings suggest that EM in a low, subantimicrobial dose has a prokinetic action on the lower esophageal sphincter. It was found that this prokinetic action is exerted most probably by stimulating cholinergic pathway and strongly suggested that 5 HT3 receptors are involved in this process. Meanwhile, the dopaminergic receptors seem to have no role in the mediation of this prokinetic action of EM. It is hoped that this prokinetic action of EM could be of a particular benefit in the improvement of GIT motility disorders. However this warrants further investigation to help more understanding of cellular mechanisms regarding that effect of EM

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