No abstract

Insulinlike growth factor-1 (IGF-1) expression is implicated in myocardial pathophysiology, and two IGF-1 mRNA splice variants have been detected in rodents, IGF-1Ea and mechano-growth factor (MGF). We investigated the expression pattern of IGF-1 gene transcripts in rat myocardium from 1 h up to 8 wks after myocardial infarction induced by left anterior descending coronary artery ligation. In addition, we characterized IGF-1 and MGF E peptide action and their respective signaling in H9C2 myocardial-like cells in vitro. IGF-1Ea and MGF expression were significantly increased, both at transcriptional and translational levels, during the late postinfarction period (4 and 8 wks) in infarcted rat myocardium. Measurements of serum IGF-1 levels in infarcted rats were initially decreased (24 h up to 1 wk) but remained unaltered throughout the late experimental phase (4 to 8 wks) compared with sham-operated rats. Furthermore, specific anti-IGF-1R neutralizing antibody failed to block the synthetic MGF E peptide action, whereas it completely blocked IGF-1 action on the proliferation of H9C2 cells. Moreover, this synthetic MGF E peptide did not activate Akt phosphorylation, whereas it activated ERK1/2 in H9C2 rat myocardial cells. These data support the role of IGF-1 expression in the myocardial repair process and suggest that synthetic MGF E peptide actions may be mediated via an IGF-1R independent pathway in rat myocardial cells, as suggested by our in vitro experiments.

Background: Muscle adaptation which occurs following eccentric exercise-induced muscle damage has been associated with an acute inflammatory response. The purpose of this study was to investigate serum interleukin-6 (IL-6), osteoprotegerin and receptor activator of nuclear factor kB ligand (OPG/ RANKL) concentrations following muscle damage. We measured changes for several days following muscle damage. Methods: Ten healthy young males performed an eccentric exercise protocol using their quadriceps. Blood samples were withdrawn before and at 6 h, 2 days, 5 days and 16 days post-exercise. Functional and clinical measurements were performed before, and on days 1, 2, 5, 8, 12 and 16 post-exercise. Results: The exercise protocol resulted in muscle damage, indicated by changes in biochemical markers. An increase in IL-6 and OPG, and a decrease in RANKL concentrations were seen at 6 h and on day 2 post-exercise; the OPG:RANKL ratio was increased at 6 h post-exercise (p-0.05). Conclusions: Changes in IL-6 and OPG/RANKL system may represent systemic responses in muscle inflammation and repair processes. However, further studies are needed to elucidate a potential systemic and/ or local role of the OPG/RANKL system in skeletal muscle repair. Clin Chem Lab Med 2009;47:777-82.

Objectives: We assessed the role of the immunogenetic background in the development and recurrence of acute idiopathic pericarditis (AIP). Methods: Fifty-five patients with a first episode of AIP were followed for 23.8 ± 6.3 months and recurrences were recorded. The control group consisted of 246 healthy individuals. In all subjects, genomic human leukocyte antigen (HLA) typing was performed. Moreover, circulating lymphocyte subpopulations were studied in 44 randomly selected patients and in 20 controls. Results: An increased frequency of HLA-A*02, -Cw*07 and -DQB1*0202 alleles, and a decreased frequency of the -DQB1*0302 allele was detected in patients with AIP. The recurrence rate was 40% and time to recurrence was 202.8 ± 164.1 days. In patients with idiopathic recurrent pericarditis (RP), increased frequencies of HLA-A*02, -Cw*07 and -DQB1*0202 alleles were found. Notably, no patient with RP exhibited HLA-DRB1*04 and -DQB1*0302 alleles. Patients with RP exhibited lower CD4+/CD45RA+ naïve T cells (p = 0.03) than controls, and higher CD8+DR+ activated T cells (p = 0.01) than patients without recurrence and controls. Conclusions: HLA alleles may confer either susceptibility or resistance to AIP and RP. Circulating T-cell subpopulations may also predict RP. A combination of the above parameters might help to better define patients prone to recurrence.

We conclude that reduced-sensitivity rather than ultra-sensitive PCR conditions correlate with clinical stage in melanoma patients.