Diagnostic and interventional radiology in liver transplantation

Diagnostic and interventional radiology play major roles in the evaluation and management of liver transplant patients. This article begins with a discussion of imaging techniques used in the preoperative evaluation of transplant candidates. Surgical approaches and normal posttransplant anatomy are presented. An in-depth discussion of the radiologic evaluation of posttransplantation complications follows, with numerous illustrative cases. Finally, the role of interventional radiology in the nonoperative management of certain complications, especially biliary problems, is discussed.     

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction,apoptosis and inflammation in rats: Possible mechanism of nephroprotection

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney.     

Marked transient alkaline phosphatemia following pediatric liver transplantation

An isolated marked transient rise in serum alkaline phosphatase levels in otherwise healthy children is a well-documented occurrence. However, in children undergoing liver transplantation, elevated alkaline phosphatase values raise the possibility of biliary obstruction, rejection, or both. During a 6-year period, 6 of 278 children undergoing liver transplantation exhibited a similar phenomenon as an isolated abnormality. None had rejection, biliary obstruction, or other allograft dysfunction during a long follow-up. Eventually and without intervention, the alkaline phosphatase levels returned to normal. These instructive cases suggest that caution be used in advocating invasive procedures if elevated alkaline phosphatase levels are an isolated abnormality, and close observation with noninvasive testing is recommended.     

Lithium and valproic acid treatments reduce PKC activation and receptor-G protein coupling in platelets of bipolar manic patients

Dysregulated protein kinase C (PKC) distribution and activation, and abnormal receptor-G protein coupling, have been implicated in the pathophysiology of bipolar affective disorder (BD). The therapeutic effectiveness of lithium has also been correlated with its ability to reduce PKC activation and G protein-mediated signaling. We examine the cellular distribution and activation of PKC and receptor-G protein coupling in blood platelets from normal controls, patients with BD mania or schizophrenia during treatment-free state, and after lithium or valproic acid administration. PKC activity was measured under basal and 50 nM phorbol 12-myristate, 13-acetate (PMA), 1 microM serotonin or 0.5 U/ml thrombin-stimulated conditions. The coupling of G proteins to serotonin or thrombin receptors were assessed by serotonin or thrombin-mediated [35S]GTPgammaS binding to membrane Galpha proteins. The results demonstrate that membrane-associated PKC activity and stimulus-induced PKC translocation are increased in BD manic, whereas stimulus-elicited PKC translocation is attenuated in schizophrenic patients. Lithium and valproic acid treatments attenuated the stimulus-induced PKC translocations to a similar degree and decreased PKC activity in both cytosolic and membranous fractions after two weeks of drug administration. An increase in 5-HT or thrombin stimulated [35S]GTPgammaS binding to Galpha proteins was detected in BD manic but not in schizophrenic patients although basal [35S]GTPgammaS binding was not different across the diagnostic groups. Lithium and valproic acid treatments similarly reduced receptor-G protein coupling with comparable time courses. Thus, increased membrane-associated PKC, cytosol to membrane PKC translocation and receptor-G protein coupling in platelets of BD manic patients were alleviated by lithium or valproic acid treatments.