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.

Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer's disease

Immunohistochemical localization of choline acetyltransferase containing neostriatal neurons and their relationship with dopaminergic synapses.

Cells of the monocyte phagocytic system can generate superoxide and glutamate anions, both of which are neurotoxic at high levels. We used rat peritoneal macrophages as a model system to test the effects of various stimulants on the production of these molecules. Glutamate production by such cells was enhanced, in a concentration-dependent manner, by treatment with serum-opsonized zymosan (OZ), lipopolysaccharide (LPS), phorbol myristate acetate (PMA), and β-amyloid peptide Aβ (1–40); but not by treatment with the reverse Aβ (40–1) or the Aβ (25–35) subfragment. Superoxide anion production by the cells was stimulated by OZ, PMA, Aβ (1–40), and Aβ (25–35). Moreover, Aβ and its subfragment, when used as priming agents, also enhanced the stimulatory effect of PMA. However, they did not act as priming agents for OZ, suggesting a competition for receptors or intracellular signaling pathways linked to those receptors. Inflammatory mediators, including Aβ, could place glutamate-sensitive neurons at risk by enhancing glutamate and oxygen free radical production by monocyte-derived cells. Such mechanisms could contribute to the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. J. Neurosci. Res. 49:229–235, 1997. © 1997 Wiley-Liss, Inc.

beta-amyloid protein enhances macrophage production of oxygen free radicals and glutamate.

Values for the catecholamine content of spinal cords of rats, rabbits, cats, humans, hogs, and oxen were obtained. The catecholamine content tended to decrease with increasing size of the species. Dopamine averaged 1.0 micrograms/g of wet tissue in the rat, and 0.2 micrograms/g in the ox; noradrenaline averaged 0.15 micrograms/g in the rat, and 0.10 micrograms/g in the ox. Adrenaline could not be detected with certainty. The catecholamine content of gray matter was much greater than that of white and seemed greater in the posterior than in the anterior part of cord. No segmental distribution was apparent. Dopamine and noradrenaline were both found in the free and bound state. Modifications to previous methods of catecholamine determinations are described. Recoveries in the analyses were determined by using radioactive tracers in preference to the usual method of doing parallel analyses. No deterioration in catecholamine content of tissues was apparent for the first 3 hours after death, but thereafter dete...

Catecholamine content of spinal cord

Lesions in Alzheimer disease are characterized by the assembly of a variety of cells and proteins associated with the immune system. Activated microglia express high levels of major histocompatibility complex glycoproteins and receptors for complement. Small numbers of T lymphocytes infiltrate tissue. Proteins of the classical complement pathway are closely connected with beta-amyloid deposits. beta-Amyloid protein binds C1q in vitro and activates the pathway. The membrane attack complex of complement, as well as proteins that defend against that complex, colocalize with dystrophic neurites. These data imply that an autodestructive process is occurring in Alzheimer disease, that overactive microglia might be responsible, and that antiinflammatory drugs might be an effective form of therapy.

Patrick L. McGeer

Papers

Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer's disease

Immunohistochemical localization of choline acetyltransferase containing neostriatal neurons and their relationship with dopaminergic synapses.

beta-amyloid protein enhances macrophage production of oxygen free radicals and glutamate.

Catecholamine content of spinal cord

Neuroimmune mechanisms in Alzheimer disease pathogenesis