Heart Remodelation: Role of MMPs

Myocardium is comprised of a number of cell types. Although most plentiful by volume, cardiac myocytes are greatly outnumbered by nonmyocyte cells, the latter constituting approximately 70% of all myocardial cells, of which approximately 90% are cardiac fibroblasts (CFBs). To maintain the integrity of the cardiac extracellular matrix (ECM) is one of the primary functions of cardiac fibroblasts. ECM represents a network structure that provides the structural and functional integrity to the heart. Besides that, it also contains a high number of cytokines and growth factors with effects on cardiac function and cardiac cells. Cardiac ECM also mediates the mechanical connection between the cardiomyocytes, CFBs, and blood. In addition to producing ECM proteins, CFBs also produce ECM-regulatory proteins – matrix metalloproteinases (MMPs), which can degrade ECM proteins – and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). To date, 26 MMPs have been cloned and characterized in vertebrates. From these, MMP1, MMP3, MMP8, MMP13, MMP2, MMP9, MMP12, MMP28, and the membrane-type MMPs (MT1-MMP/MMP14) have been identified to be involved in the myocardial remodeling. The role of higher MMPs in the cardiovascular system is less well explored

Concomitant medication of psychoses in a lifetime perspective

OBJECTIVE: Patients treated with antipsychotic drugs often receive concomitant psychotropic compounds. Few studies address this issue from a lifetime perspective. Here, an analysis is presented of the prescription pattern of such concomitant medication from the first contact with psychiatry until the last written note in the case history documents, in patients with a diagnosis of psychotic illness. METHODS: A retrospective descriptive analysis of all case history data of 66 patients diagnosed with schizophrenia or schizophrenia-like psychotic disorders. RESULTS: Benzodiazepines and benzodiazepine-related anxiolytic drugs had been prescribed to 95% of the patients, other anxiolytics, sedatives or hypnotic drugs to 61%, anti-parkinsonism drugs to 86%, and antidepressants to 56% of the patients. However, lifetime doses were small and most of the time patients had no concomitant medication. The prescribed lifetime dose of anti-parkinsonism drugs was associated with that of prescribed first-generation but not second-generation antipsychotics. CONCLUSIONS: Most psychosis patients are sometimes treated with concomitant drugs but mainly over short periods. Lifetime concomitant add-on medication at the individual patient level is variable and complex but not extensive. Copyright © 2011 John Wiley & Sons, Ltd

Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice

CONTEXT: Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. OBJECTIVE: To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. MATERIALS AND METHODS: Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests. RESULTS: 2064H was shown to bind to the serotonin 2C (5-HT(2C)) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [3H]-mesulergine with an IC(50) of 179 ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first min of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test. DISCUSSION AND CONCLUSION: Overall, manipulating the 5-HT(2C) receptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds