Perioperative interventions enhances survival and liver regeneration following extensive portal branch ligation of rabbit liver

Aim: the purpose of this study was to evaluate the effect of pharmacologic interventions in preventing liver injury, enhancing liver regeneration and prolonging survival following portal vein ligation to 80% of the liver parenchyma

Methods: rabbits underwent ligation of the portal vein branches to 80% liver parenchyma. One group of animals served as a control. The other group received pharmacologic interventions. Interventions consisted of postoperative oral 20% glucose supplementation to prevent postoperative hypoglycemia, perioperative low-molecular-weight heparin to prevent intrasinusoidal thrombosis and oral antibiotic to prevent bacterial translocation with their injurious effect on liver remnant and hepatocyte proliferation. Outcome measurements included serum liver function tests, glucose levels, and histological assessment of hepatocyte necrosis, apoptosis, mitosis and intrasinusoidal fibrin deposition and length of postoperative survival

Results: interventions improved survival in the treated group [1.07 +/- 0.07 days versus 0.71 +/- 0.1 days]. Hepatocyte necrosis [31.1 +/- 0.02 versus 51.5 +/- 0.02], apoptosis [30.4 +/- 0.02 versus 40.7 +/- 0.03] and intrasinusoidal fibrin deposition [5.6 +/- 0.8 versus 8.7 +/- 1.0] were significantly decreased and mitotic figures [29.1 +/- 2.7 versus 15.7 +/- 1.2] significantly increased in the treated group compared to control group. Biochemical markers of hepatocyte injury were not different among groups

Conclusion: pharmacologic interventions improve survival and histological evidence of remnant liver regeneration in animals subjected to portal branch ligation to 80% of rabbit liver

Telomerase assay as a prognostic marker for chemotherapy in malignancy related ascites

Chemotherapy plays a key role in the treatment of many tumors. It is difficult to determine what fraction of tumor cells survives after treatment with chemotherapeutic agents. A convenient and sensitive biochemical assay could be efficacious in determining the potential success of chemotherapy. Since telomerase activity is frequently associated with the malignant phenotype, we sought to determine whether a correlation existed between chemotherapy induced cell killing and telomerase activity. We evaluated telomerase activity in 16 malignancy related ascitic [MRAs] fluid samples [9 ovarian carcinoma and 7 hepatocellular carcinoma] before and after chemotherapy. Telomerase activity was determined using a PCR-based telomeric repeat amplification protocol coupled with ELISA. Telomerase activity was detected in 14 of 16 [87.5%] cases of peritoneal Carcinomatosis. Eight of 9 [88.9%] cases of ovarian carcinoma related ascites and 6 of 7 [85.7%] cases of hepatocellular carcinoma [HCC]-associated ascites showed telomerase activity. In contrast, overall cytological examination was positive in only 10 of 16 [62.5%]; 6 of 9 [66.7%] cases of ovarian carcinoma related ascites and 4 of 7 [57.1%] cases of HCC related ascites, We found that treatment with chemotherapeutic agents result in a decrease in the telomerase activity, which expected to be correlated with cell death. In 2 of 16 cases, telomerase activity is increased which indicates bad prognosis. Therefore, detection of telomerase activity may be a useful monitor of chemotherapeutic efficacy and an early predictor of patient outcome

Interleukin-18 and unbound vascular endothelial growth factor [VEGF] in human milk

Human milk is rich in cytokines. It contains interleukin-18 [IL-18], which is a new cytokine that induces IFN-gamma production by T cells and also contains the potent permeability and angiogenesis-promoting agent vascular endothelial growth factor [VEGF], which is a multifunctional cytokine active on blood vessel cells. The present study measured IL-18 and unbound vascular endothelial growth factor [VEGF] in the aqueous phase of human milk and examined how the concentration varied with gestational age and the duration of lactation after birth. The concentrations of IL-18 and unbound VEGF were measured by ELISA in the breast milk samples from healthy women delivering term neonates [n=69] and in colostrum from healthy women delivering preterm infants [n=18]. The highest percentages of expression for both IL-18 and unbound VEGF beyond the level of detection were observed in colostrum of fuII-term [94.4% for both cytokines] and preterm [100% and 88.9% respectively]. Colostrum contained significantly higher levels of lL-18 and unbound VEGF compared with transitional [early] milk and mature milk of full term [P< 0.001 for both cytokines]. We found also that colostrum from mothers with preterm delivery contained significantly higher concentrations of lL-18 compared with those with delivery at term [P< 0.005], but the reverse was observed as regards to unbound VEGF [P< 0.001]

Conclusion: IL-18 and unbound VEGF are present in high concentrations in breast milk, especially colostrum and may play important roles in nutrition and host defense [immunity] of high riskneonates

Soluble thrombomodulin and protein c plasma levels in neonatal sepsis

Sepsis is a systemic response to infection, and it constitutes a major cause of morbidity and mortality in Intensive Care Nursery Unit. Sepsis is associated with endothelial cell activation, a hemostatic profile characterized by activation of the coagulation pathway, and subsequent activation of the fibrinolytic system, which is then followed by the inhibition of the fibrinolytic system. Thrombomodulin [TM] is a membrane glycoprotein in the vascular endothelium and it plays an important physiological role as a cofactor in the thrombin catalyzed activation of protein C [PC]. It is also a specific parameter of endothelial cell injury. The aim of this study was to assess the plasma levels of soluble TM and PC and to clarify their relationships with the severity and outcome of neonatal sepsis. This study was carried out on 40 preterm neonates [20 septic and 20 controls] and 40 fullterm neonates [20 sepstic and 20 controls]. It was done in the Neonatal Intensive Care Unit at El-Minia University Hospital and Biochemistry Department, from December 2001 to May 2002. All neonates were subjected to full history taking stressing upon the risk factors for infection and thorough clinical examination for assessment of gestational age and detection of the clinical signs and severity of sepsis. The laboratory investigations included CBC, CRP, blood cultures and estimation of TM and PC in the plasma by ELISA technique. In this study, plasma levels of TM were significantly higher and plasma levels of PC were significantly lower in neonates with sepsis than those in the controls, in preterm than fullterm both septic and controls, in preterm cases than preterm controls and in fullterm cases than fullterm controls [all p<0.05], but no significant differences of both markers were reported between positive and negative cases of blood cultures [all p >0.5]. There was also a significant increase of TM and decreased PC plasma levels in survivors rather than non survivors both fullterm and preterm cases and in severe, complicated rather than non severe, non complicated septic cases [all p<0.05]. Significant negative correlations were reported between TM and PC in both preterm and full term cases [r=-0.46, p<0.03 and r=-0.51, p <0.02 respectively]; also between TM levels and platelet numbers in both preterm and fullterm cases [r=-0.53, p< 0.01 and r=-0.42, p<0.04 respectively]. The correlations between PC levels and platelet count were significant [r=0.5, p<0.02 for preterm cases and r=0.56, p<0.01 for fullterm cases respectively]; but there were no significant correlations between both TM and PC levels with Hb % and Ieucocytic count [all p>0.05]

Conclusion: The elevation of plasma TM is frequently seen in neonatal sepsis and circulating TM is a useful marker for evaluating endothelial tissue damage. Protein C serves as an early and highly sensitive marker for hypercoagulable state of sepsis.Both markers are useful indicators for detecting the severity and outcome of neonatal sepsis

Leucine Zipper, fyve-finger protein interacts with activating transcription factor 2 [ATF-2] and regulates its transcriptional activity

This study identified two novel proteins, 52-Zn and 67-LZ, that interact with ATF-2 in yeast two-hybrid assay. The study showed that their mRNA expression is restricted to the embryonic stage of mouse development. 52-Zn contains a putative zinc finger domain and interacts only with full-length ATF-2 in vivo. In contrast, 67-LZ contains a leucine zipper-like domain followed by a phosphatidylinositol 3-phosphate [PI3P]-binding FYVE-finger domain, is able to bind to the DNA-binding/leucine zipper domain of ATF-2 in vivo and in vitro and markedly stimulates in vitro DNA-binding by ATF-2. The ability of 67-LZ to functionally interact with ATF-2 in HeLa cell transfection assay is dependent on MEKK-1 activity, suggesting that ATF-2 phosphorylation by p38 kinase and/or Jun kinase is required for in vivo interaction between ATF-2 and this protein