2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

ACC/AHA
: American College of Cardiology/American Heart Association
ACCF/AHA
: American College of Cardiology Foundation/American Heart Association
ACE
: angiotensin-converting enzyme
ACEI
: angiotensin-converting enzyme inhibitor
ACS
: acute coronary syndrome
AF
: atrial fibrillation

/pdf/2016-esc-guidelines-for-the-diagnosis-and-treatment-of-acute-z18hg30pp1.pdf

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

/pdf/2016-esc-guidelines-for-the-diagnosis-and-treatment-of-acute-53v7yllhiz.pdf

Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...

Alzheimer's Disease: Genes, Proteins, and Therapy

NOREPINEPHRINE is found in appreciable amounts in mammalian brain tissue. VOGT (1954) showed that this amine was unequally distributed in various regions of the cat brain, the highest concentrations being found in the hypothalamus. Similar findings were reported for other animal species (BERTLER and ROSENGREN, 1959a; MCGEER, MCGEER and WADA, 1963) and man (SANO, GAMO, KAKIMOTO, TANAGUCHI, TAKE~ADA and NISHINUMA, 1959). Dopamine is also present in the brain in comparable amounts to norepinephrine (MONTAGU, 1957 ; CARLSSON, LINDQVIST, MAGNUSSON and WALDECK, 1958) but with a different regional distribution, the highest concentrations being in the corpus striatum of both animals and man (BERTLER and ROSENGREN, 1959a; SANO et al., 1959; EHRINGER and HORNYKIEWICZ, 1960; BERTLER, 1961). The anatomical distribution of these two catecholamines in the brain was confirmed by the use of fluorescent histochemical techniques which allow a precise description of the cellular localization of the amines in brain tissue (CARLSSON, FALK and HILLARP, 1962; DAHLSTROM and FUXE, 1964; FUXE, 1965). These techniques revealed that norepinephrine and dopamine are specifically localized in complex systems of neurons in the brain, a finding which lends support to the hypothesis that both amines may be neurotransmitters in the central nervous system. The metabolism of catecholamines in the rat brain was studied by introducing small amounts of radioactive norepinephrine or dopamine directly into the lateral ventricle (MILHAUD and GLOWINSKI, 1962, 1963; GLOWINSKI, KOPIN and AXELROD, 1965; GLOWINSKI, IVERSEN and AXELROD, 1966). By this approach the blood-brain barrier to catecholamines can be circumvented, penetration of the radioactive catecholamines into the brain being allowed. The disposition of PHInorepinephrine in the whole brain indicates that [3H]norepinephrine introduced into the lateral ventricle of the brain mixes with the endogenous amine and can be used as a tracer to study the biochemical behaviour of norepinephrine in the brain (GLOWINSKI and AXELROD, 1966). PHIDopamine, which is also taken up and retained in the brain, is rapidly metabolized and converted to norepinephrine (GLOWINSKI et a!., 1966). The unequal regional distribution of the endogeneous catecholamines in the brain led us to undertake a study of the disposition of radioactive norepinephrine and dopamine in various brain regions after intraventricular injection. The regional

Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain.

A chronically activated immune system can kill host cells, and accumulating evidence suggests that this mechanism plays an important role in many degenerative diseases. It may be of importance in CNS conditions such as Alzheimer's disease, ischaemia and even Parkinson's disease, as well as in peripheral disorders such as myocardial ischaemia and xenotransplantation. The complement system plays a key role in the immune reaction and can kill host tissue directly, by action of the membrane attack complex (MAC) of complement, or indirectly, through activation of macrophages which produce abundant amounts of oxygen radicals and other potentially toxic products. Endogenous regulators for many steps in the complement cascade have been identified, and these and some analogues are being explored as possible agents for the prevention of the toxic effects of complement activation. Numerous reports have attested to the protective effects of such inhibitors in animal models of immune disorders, particularly of transplant rejection and ischaemia-reperfusion injury. There have been a few clinical trials in peripheral disorders and, although not yet tried in neurological disease, it seems probable that this general approach will lead to therapeutic agents capable of specific modulation of the central immune response.

The future use of complement inhibitors for the treatment of neurological diseases.

Cross-immunity of antibodies to human choline acetyltransferase in various vertebrate species.

Microglial phagocytosis of amyloid-beta (Abeta) deposits is involved in Abeta clearance in vivo. To explore the ability of microglia to phagocytose beta, we cultured human microglia or human monocytic THP-1 cells directly on unfixed frontal cortex sections of an Alzheimer disease (AD) case. We found that when these cells were activated by lipopolysaccharide (LPS) plus interferon (IFN)-gamma, they developed ameboid morphology and formed clusters around and attaching to amyloid plaques in the tissue. Some cells adhering to these plaques internalized Abeta and some appeared to be degraded. Nevertheless, no significant reduction of the overall Abeta burden was observed. If the cells were not stimulated, they adhered poorly to the sections. We quantified THP-1 cell adhesion to an AD brain section compared with a normal brain section and found it to be significantly increased. If a brain section was rinsed with phosphate buffered saline containing 0.1% Triton X-100, most LPS/IFN-gamma-activated THP-1 cells failed to adhere. However, in co-culture with human astrocytes, the number of adherent THP-1 cells was significantly increased. These results suggest that human microglial cells are capable of adhering to and phagocytosing post mortem AD plaque material but activation may be necessary. Astrocytes may further enhance the process.

Patrick L. McGeer

Papers

The future use of complement inhibitors for the treatment of neurological diseases.

Cross-immunity of antibodies to human choline acetyltransferase in various vertebrate species.

Adhesion of exogenous human microglia and THP-1 cells to amyloid plaques of postmortem Alzheimer's disease brain.

Aromatic metabolism in schizophrenia. II. Bidimensional urinary chromatograms.

Anti-inflammatory effects of cerebrocrast in a model of rat paw edema and on mononuclear THP-1 cells.