IntroductionThe mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the ,-adrenergic agonist isoproterenol was reduced from 225±19% to 155±10% of the baseline amplitude of shortening (mean±SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell Cellular elements of the immune system have long been suspected to play a role in mediating the global myocardial dysfunction characteristic of septic shock, cardiac allograft rejection, and some forms of idiopathic cardiomyopathy (1). However, recent work indicates that direct cell-mediated cytotoxicity is not required to induce myocardial depression in experimental models of sepsis in animals or contractile dysfunction in isolated ventricular myocytes exposed to inflammatory mediators, including sera from patients with septic shock (2-5). Cell-free supernatants obtained from activated lymphocyte or macrophage cultures reversibly inhibit the expected increase in cAMP and concomitant positive inotropic responses of ventricular myocytes to the f3-adrenergic agonist isoproterenol, but they have no effect on basal cAMP levels or on baseline contractile function (2, 3). This effect of activated immune-cell-conditioned medium on myocyte responsiveness to 3 agonists is not immediate, but requires hours to become apparent ( 1).Several cytokines that are known to be present in medium conditioned by activated immune cells have been shown to induce the synthesis of isoform(s) of nitric oxide (NO) in a number of cell types and tissues (6-9). NO is now recognized to be a nearly ubiquitous autocrine and paracrine chemical messenger, with several biologic activities including the activation of soluble intracellular guanylate cyclase ( 10, 11 ). Recent evidence from this laboratory has documented a role for an endogenous, constitutively present, NO-signaling pathway in regulating the physiologic responsiveness ofneonatal and adult rat ventricular myocytes to muscarinic cholinergic and ,Badrenergic agonists, respectively ( ...

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P< .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.

Fatigue is a symptom commonly diagnosed in cancers and in many other chronic debilitating diseases and is one of the main therapeutic targets for various pharmacologic and non-pharmacologic interventions. However, in chronic obstructive pulmonary disease (COPD), this symptom, which can be considered as the main extrapulmonary clinical feature of the disease, can impact significantly on the health-related quality of life of the patients. The aims of this review are to discuss the issues related to fatigue assessment in COPD and to highlight the importance of this symptom in this setting based on the data retrieved from articles published between 1987 through August 2014 available on MEDLINE database. Fatigue can be measured by various scales or questionnaires that are designed for generic purposes or for COPD-related purposes but is still underdiagnosed and undertreated. This is due to the fact that its clinical and prognostic relevance are not appropriately acknowledged. The early identification of fatigue clinical descriptors from patients' reports could help with better management of this symptom.

Study objective. The objective of this study was to measure the phosphorylated neurofilament subunit NF-H (pNF-H)

The antioxidant potential of a new flavonic derivative named conventionally theophylline-rutoside [TR-1722] was estimated by the measurement of G-6-Pase activity (marker enzyme for the endoplasmic reticulum), catalase activity (enzyme involved in the antioxidant defence process), and total -SH groups from the hepatic homogenate, using CCl4 as a free radical generating model. To show changes in the permeability of the hepatocyte membrane, the activity of lactate dehydrogenase (LDH) in plasma was determined. The obtained results suggest that TR-1722 acts by curtailing both lipid peroxidation and alkylation processes.