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 computer support system for neurological anatomical diagnosis.

Principles of Synaptic Biochemistry

FOR some years considerable attention has been focused on the inhibitory action of γ-aminobutyric acid (GABA). One of the first systems used to demonstrate this property involved inhibition of the spontaneous discharge of the slowly adapting stretch receptor neurone of the crayfish1,2. This bio-assay procedure has been used to investigate the inhibitory characteristics of many other compounds2–4, but none reported to date has proved more active than GABA. A number of aliphatic amino- and guanidino-acids have, however, shown activity approaching that of GABA, and pre-requisites for activity appear to be the presence in the molecule of an acidic and a suitably separated basic function. Such general characteristics are to be found among the catecholamines. The inhibitory characteristics of these substances were therefore investigated.

Inhibitory Properties of the Catecholamines

It is now established that the lesions of Alzheimer disease (AD) are characterized by the presence of a broad spectrum of inflammatory molecules. They include complement proteins and their regulators, inflammatory cytokines, acute phase reactants and numerous proteases and protease inhibitors [1,2]. Several of these inflammatory products are neurotoxic and may contribute in a major way to the progressive neuronal loss of AD. Probably the most dangerous to host tissue is the complement system. It can be activated in vitro by several molecules found in AD lesions, including β-amyloid protein and C-reactive protein. Activated complement fragments richly decorate AD lesions. The membrane-attack complex of the complement is observed attached to damaged neurites. Many activated microglia are also seen clustering around AD lesions. Like all phagocytes, activated microglia produce large amounts of free radicals, glutamate and other potentially neurotoxic compounds. This is a local rather than a systemic immune reaction, with the brain cells making the inflammatory components [2]. The hypothesis that chronic inflammation may be contributing to neuronal death in AD is supported by epidemiological studies indicating that patients taking anti-inflammatory drugs, particularly of the nonsteroidal type, have a substantially reduced risk of AD [3]. In a pilot, 6-month, double-blind clinical trial, indomethacin appeared to arrest the disease [4].

Patrick L. McGeer

Papers

A computer support system for neurological anatomical diagnosis.

Principles of Synaptic Biochemistry

Inhibitory Properties of the Catecholamines

Complement, neuroinflammation and neuronal degeneration in Alzheimer disease

gamma-Glutamyltransferase activity is unchanged in acutely quinolinate-lesioned rat neostriatum but is elevated in Huntington's disease caudate.