Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients

AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from 147 PBC patients(85%female),who were followed-up for a median 89.5 mo(range 1-240).ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells,and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay.Findings were correlated with clinical data,histology,and survival.RESULTS:ANEA were detected in 69/147(46.9%) patients and 31/147(21%)were also anti-gp210 positive.The ANEA positive patients were at a more advanced histological stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ56.5%/43.5% vs 74.4%/25.6%,P=0.005)compared to the ANEA negative ones.They had a higher antimitochondrial antibodies(AMA)titer(≤1:160/>1:160 50.7%/49.3%vs 71.8%/28.2%,P=0.001)and a lower survival time(91.7 ±50.7 mo vs 101.8±55 mo,P=0.043).Moreover,they had more advanced fibrosis,portal inflammation,interface hepatitis,and proliferation of bile ductules(P =0.008,P=0.008,P=0.019,and P=0.027,respectively).They also died more frequently of hepatic failure and/or hepatocellular carcinoma(P=0.016).ANEA positive,anti-gp210 positive patients had a difference in stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ54.8%/45.2%vs 74.4%/25.6%,P= 0.006),AMA titer(≤1:160/>1:160 51.6%/48.4%vs 71.8%/28.2%,P=0.009),survival(91.1±52.9 mo vs 101.8±55 mo,P=0.009),and Mayo risk score(5.5 ±1.9 vs 5.04±1.3,P=0.04)compared to the ANEA negative patients.ANEA positive,anti-gp210 negative patients had a difference in AMA titer(≤1:160/>1:160 50%/50%vs 71.8%/28.2%,P=0.002),stage(Ⅰ-Ⅱ/Ⅲ -Ⅳ57.9%/42.1%vs 74.4%/25.6%,P=0.033),fibrosis(P=0.009),portal inflammation(P=0.018),interface hepatitis(P=0.032),and proliferation of bile ductules(P=0.031).Anti-gp210 positive patients had a worse Mayo risk score(5.5±1.9 vs 4.9±1.7,P=0.038)than the anti-gp210 negative ones.CONCLUSION:The presence of ANEA and anti-gp210 identifies a subgroup of PBC pati     

Pulmonary function at peak exercise in patients with chronic heart failure

BackgroundVarious respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients.Materials and methodsSeventy seven (66 male/11 female) patients with clinical stable CHF (age: 52 ± 11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET.ResultsPercent predicted forced expiratory volume in 1 s (FEV₁) was 91 ± 12, %predicted forced vital capacity (FVC) was 92 ± 13, %FEV₁/FVC was 81 ± 4, and %predicted IC was 85 ± 18. Peak exercise IC was lower than resting (2.4 ± 0.6 vs. 2.6 ± 0.6 l, p < 0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p < 0.001), V_E/V_CO2slope (p < 0.001), resting Pimax (p = 0.005) and post-exercise Pimax(p < 0.001). At rest, there was a statistically significant difference in end-tidal CO₂ (P_etco2) (p = 0.002), in breathing frequency (p = 0.004), in inspiratory time (Ti) (p = 0.04) and in total respiratory time (T_Tot) (p = 0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (V_E) (p < 0.001), tidal volume (V_T) (p < 0.001), respiratory cycle (V_T/T_I) (p < 0.001) and P_etco2(p < 0.001).Peak IC was correlated with peak V_O2 (r = 0.72, p < 0.001), anaerobic threshold (r = 0.71, p < 0.001), V_O2/t slope (r = 0.54, p < 0.0001), and post-exercise Pimax (r = 0.62, p < 0.001).ConclusionsIn patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.     

Solid-phase synthesis of a peptide derivative of thymosin alpha1 and initial studies on its (99m)Tc-radiolabelling

A derivative (1) of the immunopotentiating 28-peptide thymosin alpha1 has been especially designed, so that it can be (99m)Tc-radiolabelled, and synthesized following the Fmoc solid-phase peptide synthesis approach. Derivative 1 contains the N-terminal fragment Talpha1[1-14] as a bioactive segment, at the C-terminus of which a (99m)Tc-chelating moiety consisting of N(alpha),N(alpha)-dimethylglycine, serine and cysteine is linked through the N(epsilon)-amino group of a 'bifunctional' lysine residue; the latter is indirectly anchored on the solid-phase peptide synthesis resin through 6-aminocaproic acid (dmGSCK{N(epsilon)-Talpha1[1-14]}Aca). Synthetic derivative 1 was obtained at high overall yield (approximately 35%) and purity (>95%) and shown to be efficiently radiolabelled with (99m)Tc, thus resulting in the first, to our knowledge, so far reported (99m)Tc-radiolabelled derivative of thymosin alpha1, which may be eventually used as a specific molecular tool for the in vitro/in vivo study of the mode of action of the parent bioactive peptide.     

Myositis autoantibody profiles and their clinical associations in Greek patients with inflammatory myopathies

Clinical Rheumatology - Myositis-specific (MSAs) or-associated autoantibodies (MAAs) have been linked to particular clinical phenotypes of idiopathic inflammatory myopathies (IIM) and appear to aid...     

Epigenetics in hepatocellular carcinoma: An update and future therapy perspectives

Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.