Antiviral maintenance treatment with interferon and ribavirin for recurrent hepatitis C after liver transplantation: pilot study

BACKGROUND: The aim of this pilot study was to evaluate efficacy of a long-term antiviral maintenance therapy (AMT) with interferon-alpha2b and ribavirin in liver transplant recipients with recurrent hepatitis C. METHODS: Twenty-one patients with recurrent hepatitis C after liver transplantation received AMT with interferon and ribavirin, following 12 months of a basic antiviral combination treatment. Allograft function, viremia loads and allograft morphology were evaluated continuously. RESULTS: After 12 months of basic antiviral therapy, 14 patients (66.6%) had achieved initial clearance of viremia levels, and 17 recipients (81%) demonstrated normalization of allograft function, respectively. Inflammation score declined significantly (6.0 vs 3.9; P = 0.002), while stage of fibrosis remained unchanged. In virological responders maintenance therapy led to further regression of inflammation score (4.0 at baseline vs 3.1 at 24 months AMT) and fibrosis score (1.6 at baseline vs 1.1 at 24 months AMT). Despite persistence of viremia levels, continued antiviral therapy prevented progression to severe allograft inflammation in virological non-responders. Hematologic adverse effects resulted in treatment discontinuation in seven patients (33.3%). CONCLUSION: Long-term AMT, if tolerable, might be an effective approach for preventing progression to severe allograft fibrosis and thereby improving long-term survival in liver transplant recipients with recurrent hepatitis C.     

Isolated human and rat cerebral arteries constrict to increases in flow: role of 20-HETE and TP receptors

Elevation of intraluminal pressure increases vasomotor tone, which thought to have a substantial role in regulation of cerebral blood flow (CBF). Interestingly, responses of cerebral vessels to increases in flow varied and have not been studied in human cerebral arteries. We hypothesized that increases in flow elicit constrictions of isolated human and rat cerebral arteries and aimed to elucidate the underlying mechanisms. Human cerebral arteries and rat middle cerebral arteries constricted to increases in flow (P<0.05). Simultaneous increase in intraluminal flow+pressure further reduced the diameter compared with pressure-induced changes (P<0.05), leading to constant estimated CBF. Flow-induced constrictions were abolished by HET0016 (inhibitor of synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) or inhibition of COXs or blocking TP (thromboxane A₂/prostaglandin H₂, receptors and attenuated by scavenging reactive oxygen species (ROS). Flow-enhanced ROS formation was significantly reduced by HET0016. In conclusion, in human and rat cerebral arteries (1) increases in flow elicit constrictions, (2) signaling mechanism of flow-induced constriction of cerebral arteries involves enhanced production of ROS, COX activity, and mediated by 20-HETE via TP receptors, and (3) we propose that simultaneous operation of pressure- and flow-induced constrictions is necessary to provide an effective autoregulation of CBF.     

The role of FDG PET/CT for detecting the cause of fever of unknown origin in a clinical case

The fever of unknown origin from time to time constitutes a serious clinical problem and nearly all diagnostic methods are involved to discover urgently its cause. According to literature data (18)F-fluoro-deoxyglucose PET/CT was successful in 25-70% of cases even in patients without any positive findings with conventional diagnostic techniques. The Hungarian National Health Fund does not include fever of unknown origin in the list of reimbursed (18)F-fluoro-deoxyglucose PET/CT indications. The authors try to illustrate the clinical problem with this case report. Fever of unknown origin persisted in a patient for a year, but conventional diagnostic procedures were unsuccessful to find the cause of the fever. Finally, (18)F-fluoro-deoxyglucose PET/CT indicated a metabolically active focus between the pancreas tail and the spleen. After a long-lasting antibiotic therapy the patient became symptomfree.     

Treatment with a coinducer of the heat shock response delays muscle denervation in the SOD1-G93A mouse model of amyotrophic lateral sclerosis

We undertook a longitudinal study of the histological and biochemical changes at the neuromuscular junction (NMJ) in muscles of SOD1-G93A mice. We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol. Tissue samples of treated and untreated mSOD mice were analysed for AChE and ChAT enzyme activities as markers of neuromuscular function. Sections of hindlimb muscles (TA, EDL and soleus) were also stained for succinate dehydrogenase and silver cholinesterase activities as well as for immunohistochemistry. Hsp70 levels were also measured from muscle samples using ELISA. Results showed that denervation and nerve sprouting were present at symptom onset in fast muscles, although slow muscles remained fully innervated. Cholinergic enzyme activities were reduced prior to denervation and declined further with disease progression. Reduction of endplate size, a slow to fast shift in muscle phenotype was also observed. Treatment with arimoclomol delayed the appearance of these changes, increased innervation, cholinergic enzyme activities and endplate size and reversed muscle fibre transformation. These beneficial effects of arimoclomol in muscles were accompanied by an increase in Hsp70 expression. In conclusion, our results indicate that pharmacological targeting of muscles at early stages of disease may be a successful strategy to ameliorate disease progression in ALS.     

Comparative analysis of IL6 and IL6 receptor gene polymorphisms in mastocytosis

Mastocytosis is a rare disease with reported high interleukin‐6 (IL6) levels influencing disease severity. The present study investigated polymorphisms within the genes that encode IL6 and its receptor (IL6R) in relation to mastocytosis development in a case‐control design. Analysis of the IL6R Asp358Ala polymorphism showed that carriers of the AA genotype had a 2·5‐fold lower risk for mastocytosis than those with the AC or CC genotypes. No association with mastocytosis was found for the IL6−174G/C polymorphism, however, it may influence the effect of IL6R polymorphism. To the best of our knowledge this is the first study analysing IL6/IL6R polymorphisms in mastocytosis.