Insulin-like growth factors (IGF-I/-II) are not only the endocrine mediators of growth hormone-induced metabolic and anabolic actions but also polypeptides that act in a paracrine and autocrine manner to regulate cell growth, differentiation, apoptosis and transformation. The IGF system is a complex network comprised of two growth factors (IGF-I and -II), cell surface receptors (IGF-IR and -IIR), six specific high affinity binding proteins (IGFBP-I to IGFBP-6), IGFBP proteases as well as several other IGFBP-interacting molecules, which regulate and propagate IGF actions in several tissues. Besides their broad-spectrum physiological and pathophysiological functions, recent evidence suggests even a link between IGFs and different malignancies.

Background: Osteoporosis is a well‐known complication of Crohn's disease (CD). Osteoprotegerin (OPG) concentration is elevated in patients with CD compared to healthy controls. Long‐term infliximab (IFX) maintenance therapy improves the patients' bone mineral density. The effect of IFX on bone metabolism has not yet been clarified. Our aim was to evaluate IFX effects on bone pathology in CD patients. Methods: Twenty‐nine patients were treated with IFX as an induction therapy according to international guidelines at weeks 0, 2, and 6. Serum concentrations of biochemical markers of bone formation (osteocalcin, OC) and bone resorption (beta‐crosslaps, bCL), and serum concentrations of OPG and receptor activator of nuclear factor kappa B ligand (sRANKL) were measured before every treatment at days 1, 14, and 42. Results: Serum levels of OC and sRANKL increased after treatment. OC concentrations were 28.93 ± 14.95 ng/mL versus 36.33 ± 20.05 ng/mL (P < 0.005) at days 1 and 42, respectively; sRANKL concentrations were elevated from 0.0112 ± 0.028 ng/mL to 0.0411 ± 0.123 ng/mL (NS) by the end of the study. The concentrations of both bCL and OPG decreased. bCL concentrations were 0.636 ± 0.594 versus 0.519 ± 0.235 (NS) at days 1 and 42, respectively, while OPG concentration decreased from 3.739 ± 1.485 to 3.491 ± 1.618 (P < 0,05). Conclusions: IFX therapy decreased the OPG concentration in CD patients significantly. In parallel, the serum bone resorption marker (bCL) also decreased. Concentrations of bone formation marker (OC) and sRANKL increased during the same period; however, those changes were not statistically significant. Elevated OPG in CD could be a counter‐regulatory response to inflammatory cytokines or may reflect T‐cell activation. (Inflamm Bowel Dis 2007)

Since Kerr described programmed cell death (apoptosis) as a process distinct from necrosis, there have been many studies of apoptosis in disease, especially of immunological origin. Because cardiac myocytes are terminally differentiated cells, they have typically been assumed to die exclusively by necrosis. However, during the last decade this view has been challenged by several studies demonstrating that a significant number of cardiac myocytes undergo apoptosis in myocardial infarction, heart failure, myocarditis, arrhythmogenic right ventricular dysplasia, and immune rejection after cardiac transplantation, as well as in other conditions of stress. These are potentially relevant observations, because apoptosis--unlike necrosis--can be blocked or reversed at early stages. Specific inhibition of this process may confer a considerable degree of cardioprotection, but requires a thorough understanding of the underlying mechanisms. Recent progress includes a better understanding of the importance of mitochondria-initiated events in cardiac myocyte apoptosis, of factors inducing apoptosis in heart failure and during hypoxia, and of the dual pro-apoptotic and anti-apoptotic effects of hypertrophic stimuli such as beta-adrenoceptor agonists, angiotensin converting enzyme inhibitors, nitric oxide and calcineurin. The investigation of cytoprotective and apoptotic signal transduction pathways has revealed important new insights into the roles of the mitogen-activated protein kinases p38, extracellular signal regulated kinase and c-Jun N-terminal kinase in cardiac cell fate. Our present review focuses on the intracellular signal transduction pathways of cardiac myocyte apoptosis and the possibility of specific inhibition of the process.

Infliximab induction therapy alone may result in sustained remission mainly in patients with luminal disease. These results suggest the need for maintenance therapy with infliximab after successful therapy induction in patients with fistulae, while luminal CD patients could possibly participate in regular retreatment only if needed. If these data are confirmed, this modification of the therapeutic procedure could well increase the cost-effectiveness of infliximab.

Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-I and TNF-a activity, compared with that from age-and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.

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