Changes of adiponectin oligomer composition by moderate weight reduction

Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.     

Different prognostic importance of elevated troponin I after percutaneous coronary intervention in acute coronary syndrome and stable angina pectoris

OBJECTIVES: To investigate the prognostic importance of cardiac troponin I (cTnI) elevation after percutaneous coronary intervention (PCI) in different clinical settings. DESIGN: The study includes 238 patients presenting with acute coronary syndrome (ACS) and 194 patients with stable angina pectoris (SAP). The composite end point of death or hospitalization due to non-fatal myocardial infarction, repeated revascularization or unstable angina, was determined during one year of follow-up. RESULTS: cTnI elevation after PCI was more frequent in ACS patients than SAP patients. ACS patients with cTnI elevation after PCI had significantly higher number of events than patients with unchanged cTnI status after PCI. SAP patients had generally lower event rate than ACS patients. The event rate was also significantly higher among ACS patients than SAP patients at comparable degrees of cTnI elevation after PCI. There was no difference in events among SAP patients with or without cTnI elevation after PCI. CONCLUSION: cTnI elevation after PCI predicts adverse outcome after one year in patients with ACS, but not in patients with SAP.     

A prospective study on size and function of paediatric kidneys (<10 years) transplanted to adults

BACKGROUND: There is increasing evidence that paediatric kidneys transplanted to adults have good graft function and satisfactory graft survival. The relationship between size increment and functional potential of paediatric kidneys following transplantation is not defined in detail. We therefore initiated a prospective single centre study, comprising detailed and repeated measurements of size and function of paediatric kidneys transplanted to adults. METHODS: Nineteen adults receiving a first kidney transplant from a paediatric donor (<10 years of age) were included in the study. All patients were followed for 12 months post-transplant. Increment in size and function of the transplanted kidneys were assessed by ultrasound, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). All tests were performed during the first week, post-transplant and subsequently repeated at 1, 3, 6 and 12 months. RESULTS: Kidney volume increased 2.6-fold at 12 months (P < 0.001). GFR and ERPF showed a slightly more moderate increase, 1.8-fold and 1.6-fold, respectively. Patient and graft survival at 1 year were 100% and serum creatinine was 91 micromol/l (66-169). CONCLUSION: The study indicates that paediatric kidneys for transplantation may be considered as excellent rather than being referred to as suboptimal for adult recipients, at least the first year after transplantation.     

Mechanical restitution curves: a possible load independent assessment of contractile function.

OBJECTIVE: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload. METHODS: Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm. RESULTS: Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways). CONCLUSIONS: We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.     

Clinical relevance of autoantibodies after pediatric liver transplantation

BACKGROUND: The presence of autoantibodies and development of autoimmune hepatitis after liver transplantation has recently been reported as one of the causes for chronic graft dysfunction. The pathogenesis and clinical significance of this disease still remains unclear. METHODS: We evaluate 96 patients for the prevalence of autoantibodies and autoimmune hepatitis after pediatric liver transplantation and review their clinical follow-up including virus serologies, ultrasound examination and liver biopsies. RESULTS: Positive autoantibodies were detected in 74% of the patients after pediatric OLT. Graft dysfunction was observed in 46% of these children, and in 35% of the transplant recipients seronegative for autoantibodies. None of the patients showed histological signs or fulfilled clinical criteria for de novo autoimmune hepatitis. One child with negative autoantibodies was diagnosed to have a histologically proven de novo AIH two yr following OLT. CONCLUSIONS: There is a high prevalence of autoantibodies after pediatric OLT, but the incidence of de novo AIH is very rare. In transplant recipients showing elevated liver function tests de novo autoimmune hepatitis has to be excluded by liver biopsy even if the patient is seronegative for autoantibodies.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Humorale Vaskulitisdiagnostik bei peripherer arterieller Verschlusskrankheit

BACKGROUND: In patients with early manifestation of peripheral arterial occlusive disease (PAOD) and a less classical atherosclerotic risk profile, vasculitis is presumed to be the underlying disease. We performed a prospective study of the importance of determination of autoantibodies used for the diagnosis of vasculitis and collagen diseases in patients with symptomatic PAOD. PATIENTS AND METHOD: 698 consecutive patients (mean age +/- SD: 68 +/- 10 years) were included who were referred from 1998 to 1999 for interventional treatment of PAOD. In 121 PAOD-patients (61 +/- 12 years) with a less pronounced atherosclerotic risk profile, or rarefied distal arteries without sclerosis of the media, or elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) independent from the stage IV of PAOD, the following autoantibodies were investigated: antinuclear antibodies (ANA), antibodies against extractable nuclear antigens (ENA): SCL 70, RNP, SS-A, SS-B, Jo-1, SM), double-stranded DNA antibodies (ds-DNA), antineutrophil cytoplasmatic antibodies (c- and p-ANCA), antiphospholipid antibodies [phosphatidylserine (APSA) and beta(2)-glycoprotein], smooth (SMA) and striated muscle (StrMA). ANA, SMA and StrMA were estimated by indirect immunofluorescence technique, ENA by Western-blot and the others by enzyme linked immunoassay. RESULTS: 38 PAOD-patients (35%) had increased autoantibody concentrations. The rate of different PAOD stages and localization did not differ between the group of patients with increased autoantibody concentrations and the group of patients without. But the group of patients with increased autoantibody concentrations had higher rates of elevated ESR [p-value of 0.0043, odds ratio of 7.1 (95% CI: 1.49-33.81)]. ANA were the most frequent autoantibodies detected in 17 (14%) of the 121 patients followed by APSA and autoantibodies directed against beta(2)-glycoprotein. During follow-up of 24 +/- 6 months no vasculitis or collagen diseases associated with the elevated autoantibody concentrations became clinically manifest in the 38 patients. Two patients died due to coronary heart disease. Four patients had a worsening of their PAOD but no amputation was performed. Out of the 83 patients without elevated concentrations of autoantibodies, eight patients died and three amputations were carried out. CONCLUSION: All in all, increased autoantibody concentrations in patients suffering from peripheral atherosclerosis are not a rare finding. A systematic determination of autoantibodies, especially in patients with a low atherosclerotic risk profile, does not increase the number of manifest or developing vasculitis of collagen disease.