State of the iron metabolism in patients with chronic hepatitis C type C does not influence antiviral treatment with interferon and ribavirin

BACKGROUND/AIMS: Comparison of the iron status in patients who responded and did not respond to combination treatment with interferon alpha and ribavirin in chronic hepatitis C. METHODOLOGY: The study group comprised of 61 patients with chronic hepatitis C (genotype 1) treated with alpha 2b interferon and ribavirin. The iron metabolism was evaluated based on serum iron level, total iron binding capacity, transferrin saturation, serum ferritin concentration and hepatic iron concentration. In the evaluation of antiviral treatment efficacy biochemical and virological responses were taken into account. RESULTS: End of treatment response was observed in 38 patients (62%). Significant differences in iron parameters were not observed between responders and non-responders. Also, sustained viral response, 6 months after treatment completion, was reached in 32 patients (52.5%). Iron metabolism parameters did not differ significantly in the group of sustained responders versus non- responders. Finally, ALT normalization was observed in 42 patients (68.9%). Again, no significant differences in iron status were observed between patients with and without biochemical response excluding significantly higher serum ferritin concentration in non-responders. CONCLUSIONS: Results of this study show that iron status does not significantly influence the efficacy of treatment with interferon and ribavirin in patients with chronic hepatitis C.     

Mass spectral characterization of peptide transmitters/hormones in the nervous system and neuroendocrine organs of the American lobster Homarus americanus

The American lobster Homarus americanus is a decapod crustacean with both high economic and scientific importance. To facilitate physiological investigations of peptide transmitter/hormone function in this species, we have used matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nanoscale liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry (nanoLC-ESI-Q-TOF MS/MS) to elucidate the peptidome present in its nervous system and neuroendocrine organs. In total, 84 peptides were identified, including 27 previously known H. americanus peptides (e.g., VYRKPPFNGSIFamide [Val(1)-SIFamide]), 23 peptides characterized previously from other decapods, but new to the American lobster (e.g., pQTFQYSRGWTNamide [Arg(7)-corazonin]), and 34 new peptides de novo sequenced/detected for the first time in this study. Of particular note are a novel B-type allatostatin (TNWNKFQGSWamide) and several novel FMRFamide-related peptides, including an unsulfated analog of sulfakinin (GGGEYDDYGHLRFamide), two myosuppressins (QDLDHVFLRFamide and pQDLDHVFLRFamide), and a collection of short neuropeptide F isoforms (e.g., DTSTPALRLRFamide and FEPSLRLRFamide). Our data also include the first detection of multiple tachykinin-related peptides in a non-brachyuran decapod, as well as the identification of potential individual-specific variants of orcokinin and orcomyotropin-related peptide. Taken collectively, our results not only expand greatly the number of known H. americanus neuropeptides, but also provide a framework for future studies on the physiological roles played by these molecules in this commercially and scientifically important species.     

Stimulant Injectors in Ukraine: The Next Wave of the Epidemic?

This study was designed to assess differences in drug and sex-related risk behaviors between injectors of opiates only, opiate/sedative mix only and stimulants only. Participants were current out-of-treatment injection drug users (IDUs), unaware of their HIV status, recruited through street outreach in Kiev, Odessa and Makeevka/Donetsk, Ukraine. Overall, 22% tested positive for HIV, including 39% among opiate/sedative injectors, 19% among opiate injectors and 17% among stimulant injectors. Despite these differences, stimulant injectors were at higher risk than other IDUs in sharing a used needle/syringe, always injecting with others, injecting a drug solution drawn from a common container, having an IDU sex partner, not using condoms during vaginal or anal sex and on composite measures of injection and sex risks. After controlling for age differences, stimulant injectors remained at higher risk in their needle and sex risk behaviors. Without intervention, it is likely that HIV will increase among stimulant injectors.     

Renal insufficiency increases mortality in acute coronary syndromes regardless of TIMI risk score

BACKGROUND: Non ST-segment elevation acute coronary syndromes (NSTE ACS) are the most frequent cause of admission to intensive care units. Early risk assessment and implementation of optimal treatment are of special importance in these patients. Previous studies have demonstrated that renal insufficiency is an independent risk factor in patients with cardiovascular disease. AIM: To assess the effects of renal function on the course of treatment and prognosis in patients with NSTE ACS admitted to hospitals without on-site invasive facilities but with a possibility of immediate transfer to a reference centre with a catheterisation laboratory. METHODS: Twenty-nine community hospitals without on-site invasive facilities participated in the Krakow Registry of Acute Coronary Syndromes - a prospective, multicentre, web-based, observational registry. Renal insufficiency (RI) was defined as creatinine clearance (CrCl) <60 ml/min. RESULTS: NSTE ACS was diagnosed in 1396 patients. Renal insufficiency was diagnosed in 34% of all patients. Only 17% of them had been diagnosed with RI prior to admission. Transfer for invasive treatment was undertaken in 10% of RI patients as compared to 16% of patients with CrCl >60 ml/min (NS). In-hospital mortality among patients remaining on conservative treatment in community hospitals was significantly higher among RI patients (4.0 vs. 0.6%; p <0.001). Thienopyridines were less frequently used in RI patients (46 vs. 54%; p <0.05). In-hospital mortality among RI patients remaining in community hospitals and treated conservatively was higher than among non-RI patients in each TIMI risk score group: 7.3 vs. 2.4% (p <0.05) in the high risk group, 4.1 vs. 1.4% (NS) in the moderate and 3.6 vs. 0% (p <0.001) in the low risk group. Multivariate logistic regression analysis identified reduced creatinine clearance and a history of heart failure as independent factors influencing mortality. CONCLUSIONS: Renal insufficiency was present in one-third of NSTE ACS patients. Patients with renal insufficiency had worse clinical risk profile and received less aggressive treatment. Patients with NSTE ACS and renal insufficiency treated conservatively had higher in-hospital mortality. Renal insufficiency modifies mortality irrespective of the TIMI risk score. Creatinine clearance should be considered in modification of the TIMI risk score scale.     

Pericarditis as a consequence and first symptom of microcellular lung carcinoma--case report

A case of a patient suffering from Streptococcal suppurative pericarditis with cardiac tamponade and acute renal failure as a first symptom of disseminated lung cancer is presented. The examination of pericardial fluid only confirmed Streptococcal infection as a cause of exudative pericarditis. The neoplasmatic cells were not found in the examined fluid. Next, chest CT and bronchoscopy were performed due to the lack of clinical improvement, recurrence of severe pericardial effusion and enlargement of the upper mediastinum found on chest radiogram. CT and bronchoscopy allowed to establish the final diagnosis - disseminated lung cancer.     

Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and cardiovascular risk factors in middle-aged men

Adiponectin, an adipocyte-derived protein, seems to be a link between obesity, insulin resistance, and atherosclerosis. The present study investigated the association between adiponectin and coronary artery disease in middle-aged men. Material and methods: We examined 48 men (aged 40–60) with angiographically confirmed coronary atherosclerosis and 19 healthy men, matched by age, as a control group. Concentrations of glucose and lipids were estimated with enzymatic methods. Plasma level of adiponectin, total and free testosterone, estradiol, estrone, DHEA-S, and insulin were estimated with RIA commercial kits. Results: Men with coronary atherosclerosis had lower plasma adiponectin level than controls (16.2±9.2 vs 20.5±6.7 μg/mL; p<0.05). However, after including BMI and waist as covariate data in ANCOVA, the difference in adiponectin levels between men with CAD and controls lost statistical significance (respectively for BMI and waist: p=0.4 and p=0.7). Moreover, although not significant, adiponectin levels decreased as a function of the number of significantly narrowed coronary arteries. In a priori comparison the lowest adiponectin plasma concentration was in men with three-vessel coronary artery disease (14.3±9.8 μg/mL) and the highest in controls (20.5±6.8 μg/mL; p=0.09). Adiponectin plasma level correlated negatively (p<0.05) with BMI, waist, percentage of total fat, fasting-insulin-resistance index (FIRI), total cholesterol and triglycerides, and positively with quantitative insulin sensitivity check index (QUICKI), HDL cholesterol, total testosterone, and total testosterone/estradiol ratio. Conclusions: Our data suggest that low plasma adiponectin level is connected with insulin resistance syndrome and atherogenic lipid profile. It seems that adiponectin plays a role in pathogenesis of coronary atherosclerosis, especially in obese and insulin-resistant subjects.     

Ultrastructure of oval cells in children with chronic hepatitis B, with special emphasis on the stage of liver fibrosis： The first pediatric study

AIM:To investigate the ultrastructure of oval cells in children with chronic hepatitis B,with special emphasis on their location in areas of collagen fibroplasia. METHODS:Morphological investigations were conducted on biopsy material obtained from 40 children,aged 3-16 years with chronic hepatitis B. The stage of fibrosis was assessed histologically using the arbitrary semiquantitative numerical scoring system proposed by Ishak et al. The material for ultrastructural investigation was fixed in glutaraldehyde and paraformaldehyde and processed for transmission-electron microscopic analysis. RESULTS:Ultrastructural examination of biopsy specimens obtained from children with chronic hepatitis B showed the presence of two types of oval cells,the hepatic progenitor cells and intermediate hepatic-like cells. These cells were present in the parenchyma and were seen most commonly in areas of intense periportal fibrosis (at least stage 2 according to Ishak et al) and in the vicinity of the limiting plate of the lobule. The activated nonparenchymal hepatic cells,i.e. transformed hepatic stellate cells and Kupffer cells were seen in close proximity to the intermediate hepatic-like cells. CONCLUSION:We found a distinct relationship between the prevalence of oval cells (hepatic progenitor cells and intermediate hepatocyte-like cells) and fibrosis stage in pediatric patients with chronic hepatitis B.     

Effects of L-arginine supplementation on endothelial function after stent implantation

BACKGROUND: In-stent restenosis after percutaneous coronary intervention (PCI) is due to the proliferation of intima. Supplementation with L-arginine has been shown to improve endothelial function and decrease neointima proliferation in experimental animal model of restenosis. AIM: To assess the effects of L-arginine supplementation on neointima proliferation and endothelial markers as well as growth factor levels in patients after stent implantation. METHODS: In this prospective, randomised, double-blind, placebo-controlled study 60 patients undergoing stent implantation received placebo or L-arginine (200 mg/kg infused intravenously over 4 hours, 12 and 3 hours before PCI, and 500 mg over 10 minutes prior to stent implantation, followed by oral supplementation of 6 g/day for 14 days after PCI). Quantitative coronary angiography (QCA) and intracoronary ultrasonography (ICUS) were performed at baseline and after a seven-month follow-up period. Serum concentration of L-arginine was measured at baseline, before PCI, 24 hours after PCI, and 7 as well as 14 days after PCI. The transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF) and endothelin levels were assessed before PCI, and 24 hours as well as 14 days after the procedure. RESULTS: No significant differences in the QCA or ICUS parameters were found between patients receiving L-arginine or placebo. 24 hours after stent implantation patients who received placebo had significantly a higher increase in the endothelin serum concentration and a lower rise in the VEGF level than the patients who received L-arginine (92.6+/-49 pg/ml vs 76.1+/-27 pg/ml, p<0.05, and 10 pg/ml vs 17.6+/-12 pg/ml, p<0.05, respectively). The TGF-beta level, assessed 14 days after PCI, was significantly higher in the placebo group than in the L-arginine group (14.8+/-10 ng/ml vs 11.2+/-6.1 ng/ml, p<0.05). CONCLUSIONS: In spite of favourable changes in the vascular endothelial biochemical marker profile, supplementation with L-arginine did not decrease the in-stent reocclusion rate.     

Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma

Mutations that inactivate either TSC1 or TSC2 cause tuberous sclerosis. We have used immunoblotting and immunohistochemical analysis to see whether there is phosphorylation of p70 S6 kinase, and the ribosomal S6 protein in angiomyolipomas occurring in tuberous scierosis. Hamartin (encoded by TSC1) and S6K was expressed in all samples. Tuberin (TSC2) was weak or absent in angiomyolipomas, but present in healthy kidney, whereas, phosphorylated p70 S6 kinase and p56 were present only in angiomyolipomas. Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth. We suggest that treatment with rapamycin and its analogues could benefit such patients.     

Intracoronary administration of the combined fibrinolytic therapy a in patient with acute myocardial infarction and end-stage coronary heart disease - a case report

Classical thrombolytic treatment in acute myocardial infarction is able to reach reperfusion in 60-80% of patients, however in 5-10% of cases reoclusion occurs. Primary percutaneous coronary intervention (PCI) offers the potential for a higher rate of reperfusion and a lower rate of bleeding events. Recently, advances in platelet inhibition and PCI procedures have led to the combination of all the approaches. Facilitated PCI or the use of elective PCI after pharmacological reperfusion therapy can combine the best aspects of thrombolysis and mechanical revascularization in acute myocardial infarction. However, in some cases PCI cannot be performed. This paper describes a patient with acute myocardial infarction successfully treated with intracoronary infusion of alteplase and GP IIb/IIIa inhibitor.