Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model

INTRODUCTIONReperfusion injury after cold preservation is associatedwith the occurrence of primary non-function and delayedgraft function, which predisposes allografts to acuteand chronic rejection[1]. Despite these obstacles, organtransplantation has bec…     

Polyethylene glycol rinse solution:An effective way to prevent ischemia-reperfusion injury

AIM:To test whether a new rinse solution containing polyethylene glycol 35(PEG-35)could prevent ischemia-reperfusion injury(IRI)in liver grafts.METHODS:Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions(Ringer’s lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L)before ex vivo perfusion with Krebs-Heinseleit buffer solution.We assessed the following:liver injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity),liver function(bile output and vascular resistance),oxidative stress(malondialdehyde),nitric oxide,liver autophagy(Beclin-1 and LCB3)and cytoskeleton integrity(filament and globular actin fraction);as well as levels of metalloproteinases(MMP2 and MMP9),adenosine monophosphate-activated protein kinase(AMPK),heat shock protein 70(HSP70)and heme oxygenase 1(HO-1).RESULTS:When we used the PEG-35 rinse solution,reduced hepatic injury and improved liver function were noted after reperfusion.The PEG-35 rinse solution prevented oxidative stress,mitochondrial damage,and liver autophagy.Further,it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70,activated AMPK,and contributed to the restoration of cytoskeleton integrity after IRI.CONCLUSION:Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI.     

Alterations in lipidic metabolism in hemodialysis patients

Background: Chronic kidney failure is associated with dyslipidemia and accelerated atherosclerosis. Aim: To study lipidic metabolism alterations in patients with chronic kidney failure on hemodialysis. Methods: The study interested 45 hemodialysis patients with a mean age of 49.04 ±15.92 years old and 45 healthy controls. A blood sample was collected from each patient and control to measure total cholesterol, triglycerides, HDL- cholesterol, LDL-cholesterol, apolipoproteins AI and B100, lipoprotein (a) and C Reactive Protein. Results: A significant increase of serum triglycerides (p= 0.002), lipoprotein (a) (p = 0.001) and C Reactive Protein (p = 0.008) was observed in patients when compared with healthy controls. A significant decrease of serum total cholesterol (p=0.01), HDLcholesterol (p<0.001), LDL-cholesterol (p=0.005) and apolipoprotein AI (p<0.001) was also observed in patients. Conclusion: Disorders of lipidic metabolism are frequent in hemodialysis patients. These alterations can lead to cardiovascular disease in uremic patients.     

High-Na + low-K + UW cold storage solution reduces reperfusion injuries of the rat liver graft

The isolated perfused rat liver model was used to assess graft viability after 24 h of cold preservation. Two solutions were compared for liver preservation: Belzer's original UW solution (high-K ⁺ UW) and a solution containing the same components but with inverted concentrations of sodium and potassium (high-Na ⁺ UW). During the 120 min of normothermic reperfusion, livers preserved in the high-Na ⁺ UW solution released lower levels of creatine kinase-BB isoenzyme, transaminases (ALT and AST), and potassium than those preserved in the high-K ⁺ UW solution. Bile flow and biliary excretion of indocyanine green increased when livers were preserved in the high-Na ⁺ UW solution. We found no statistical differences for oxygen consumption and tissue ATP concentration. The results of this study support the concept that a high-Na ⁺ UW solution is a more effective means of preserving rat livers, at least after 24 h of cold-storage and 120 min of reperfusion in the isolated perfused model, than the original high-K ⁺ UW solution. Liver preservation in the high-Na ⁺ UW solution reduces damage to sinusoidal endothelial and hepatocellular cells. The use of an extracellular-like Belzer cold storage solution eliminates potassium-related problems in cold preservation and subsequent normothermic reperfusion while keeping all the qualities of the original UW solution. Received: 26 August 1997 Received after revision: 12 November 1997 Accepted: 28 November 1997     

Hypoglycaemic and Antihyperglycaemic Activity of Ageratum Conyzoides L. in Rats

The hypoglycaemic and antihyperglycaemic properties of the aqueous extracts of the leaves of Ageratum conyzoides L. were evaluated in normoglycemic and in streptozotocin-induced diabetic rats, in order to validate its use in folk medicine. Tested animals were given the aqueous extracts of the plant at the doses of 100, 200 and 300mg/kg. These doses were tested also on glucose loaded normal male rats (Oral Glucose Tolerance Test). Of all the doses, the aqueous extracts at 200 and 300mg/kg showed statistically significant hypoglycaemic and antihyperglycaemic activities. For the oral glucose tolerance test, 100mg/kg dose only attenuated significantly the rise of blood glucose in normal fasted rats. Consequently, these results confirmed the hypoglycaemic properties of the leaves of Ageratum conyzoides.     

Conservative mutations in the putative metal-binding region of human immunodeficiency virus tat disrupt virus replication

The tat trans-activator proteins of the primate immunodeficiency viruses contain a highly conserved cysteine-rich domain. In human immunodeficiency virus type 1 tat there are seven cysteines located between residues 22 and 37 that are thought to form a metal-nucleic acid-binding structure. Most of the previous mutagenesis studies had demonstrated that these residues are essential for tat activity and virus expression. Here we show that potentially conserved cysteine-histidine substitutions within the proposed tetrahedral structure still eliminate tat activity and virus expression. Consistent with previous studies, one cysteine-to-histidine mutation (amino acid 31) had little effect on trans-activation. We have studied the functional properties, stability and subcellular localization of several tat protein mutants. Most of the mutants are stable and properly localized to the nucleus and/or nucleolus. However, cysteine-to-glycine at position 34 affected tat stability. Our studies with the histidine mutants suggest that tat does not assume the prototype "zinc finger" structure for metal binding.     

Role of sirtuins in ischemia-reperfusion injury

Ischemia-reperfusion injury(IRI)remains an unresolved and complicated situation in clinical practice,especially in the case of organ transplantation.Several factors contribute to its complexity;the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury.Recently,the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers,due to their involvement in the modulation of a wide variety of cellular functions.There are seven mammalian sirtuins and,among them,the nuclear/cytoplasmic sirtuin 1(SIRT1)and the mitochondrial sirtuin 3(SIRT3)are ubiquitously expressed in many tissue types.Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways,which are key processes during IRI.In this review,we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress,apoptosis,microcirculatory stress and inflammation during reperfusion.We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.     

Intracranial tumor developing from the vitelline sac. Apropos of a case

The authors report a case of a primary intracranial yolk sac tumor which is a quite rare eventuality. The patient, an 18 months old girl was referred for severe intracranial hypertension. Neurological examination revealed a right hemiparesis, a left abducens nerve palsy and a bilateral papilledema. The serum and C.S.F. levels of alpha fetoprotein were at 2100 Ugr/l and 2500 Ugr/l, respectively. The computerized tomography showed a mass with a low density area in the left temporoparietal lobe and the carotid angiogram a highly hyper-vascular tumor. The child underwent a left temporo-parietal craniotomy and the friable vascular tumor was totally removed. A radiotherapy was associated to the surgical treatment. Histologically, glomerular like structures (Shiller Duval body), intra and extra cellular hyaline globules PAS positive were frequently seen. The tumor marker was demonstrated immunohistochemically.