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.

The spatial pattern of β-amyloid protein (BAP) deposits in Alzheimer's disease cerebral cortex was investigated. In cortical areas where the accumulation of BAP was relatively sparse, the deposits tended to accumulate vertically in a columnar arrangement. Typically, these aggregates consisted of both consolidated and diffuse deposits approximately 200 to 600 μm in width. Blood vessels running perpendicularly to the pial surface were sometimes observed penetrating the center of these colunms, but this was not a consistent finding. These BAP extracellular aggregates might be related to the columnar organization of the cerebral cortex.

Columnar arragement of β-amyloid protein deposits in the cerebral cortex of patients with Alzheimer's disease

The amyloid cascade hypothesis postulates that accumulation of beta-amyloid (Abeta) plays a key role in the development of Alzheimer's disease (AD) Accordingly, much effort has gone into reducing the amyloid burden, especially in transgenic mice expressing mutations in human amyloid precursor protein Such mice develop amyloid plaques but not neurofibrillary tangles Immunization with Abeta and other inflammatory stimuli, inhibitors of Abeta formation, cholesterol lowering agents, beta-sheet breaker peptides, antioxidants and various miscellaneous agents have been found to reduce the more soluble Abeta in such transgenic mice Whether they would affect the more consolidated, cross-linked Abeta of AD and, if they did, whether that would really prove an effective treatment for the disease remains for future research to determine

Abeta immunotherapy and other means to remove amyloid.

Induction of complement C9 messenger RNAs in human neuronal cells by inflammatory stimuli: relevance to neurodegenerative disorders.

McGeer, Patrick L., Edith G. McGeer, Hisaki Kamo and Kathy Wong: Positron emission tomography and the possible origins of cytopathology in Alzheimer's disease. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1986, 10 (3–5): 501–518. 1. 1. The local cerebral metabolic rate for glucose (LCMRgl), as determined by positron emission tomography (PET), declines in the cerebral cortex in Alzheimer's disease; the severity of the decline parallels the severity of the dementia and correlates with regional cortical neuronal loss and glial proliferation. 2. 2. The cholinergic cells of the medial basal forebrain show a pathological dropout in Alzheimer's disease which accounts for the decline in choline acetyltransferase in the cerebral cortex and hippocampus. 3. 3. It is proposed that these cholinergic cells serve both as an acquisition and readout device for memory; reconstruction of real time events can thus be created in the areas of neocortex where consciousness resides. 4. 4. Alzheimer's disease may have a toxic, genetic or infectious origin; electron microscopic evidence is presented for the possible presence of viral particles of the double stranded DNA type in Alzheimer's brain tissue.

Patrick L. McGeer

Papers

Columnar arragement of β-amyloid protein deposits in the cerebral cortex of patients with Alzheimer's disease

Abeta immunotherapy and other means to remove amyloid.

Induction of complement C9 messenger RNAs in human neuronal cells by inflammatory stimuli: relevance to neurodegenerative disorders.

Positron emission tomography and the possible origins of cytopathology in Alzheimer's disease.

Cholinergic systems in extrapyramidal function.