Muscle NAD+ depletion and Serpina3n as molecular determinants of murine cancer cachexia—the effects of blocking myostatin and activins

Objective Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome. Methods Healthy and C26 tumour-bearing (TB) mice were treated with recombinant sACVR. The sACVR or PBS control were administered either prior to the tumour formation or by continued administration before and after tumour formation. Muscles were an…

Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta.

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-beta was measured by bioassay and by ELISA in serum samples taken at t…

Evidence for a respiration-modulated cholinergic action on the activity of medullary respiration-related neurons in the rabbit. An iontophoretic study.

Effects of the iontophoretically administered cholinergic agonists acetylcholine, bethanechol and DMPP on the activity of medullary respiration-related neurons were examined in urethane-anaesthetized rabbits. Inhibitory effects prevailed over excitatory effects. Analysis of cholinergic effects by cycle-triggered averaging revealed three major types of neuronal responses: (i) constant alterations of spike-density throughout the whole period of activity ("constant effects"), (ii) effects increasing during the progression of the burst of discharge or effects restricted to a particular fraction of the burst ("phasic effects") and (iii) effects which were characterized by an excitation during on…

Molekulare Zielstrukturen f�r die Therapie des Bronchialkarzinoms