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 effect of cannabinoids on the number of nuclear membrane-attached ribosomes in infant rat brain.

Localization of acidic fibroblast growth factor (aFGF) was investigated immunohistochemically in postmortem brain tissue of Alzheimer''s disease (AD), amyotrophic lateral sclerosis (ALS), and age-matc

Reactive Astrocytes Express Acidic Fibroblast Growth Factor in Alzheimer's Disease Brain

P3-288: Beta amyloid deposition in the atrophic form of general paresis

Systems model of cortical organization: Positron emission tomography and neuropsychological test performance

Marinesco bodies (MBs) were originally described in 1902 [11]. They are small, spherical intranuclear inclusions that are observed in neurons of the substantia nigra (SN) and locus coeruleus (LC). They have traditionally been considered to be benign. However, there is increasing evidence that they may be an early signal of neuronal dysfunction. They appear in neurons with a high content of melanin, suggesting their association with particular oxidative processes. They are ubiquitinated [1], indicating contents targeted for degradation through the ubiquitin-proteasomal pathway. Their numbers increase with age in both humans [2, 19] and monkeys [10, 17]. This contrasts with losses during aging of SN and LC neurons. More than 40% of SN neurons can be lost without onset of extrapyramidal signs [4, 13]. Why these neurons drop out with aging is unknown but oxidative stress from high levels of catecholamine turnover is a possibility. A relationship between catecholamine turnover and the appearance of MBs has been indicated by the report of Beach et al. [2] of an inverse correlation of dopaminergic markers in the basal ganglia with the number of MBs in SN. They found MB density to be highest in diffuse Lewy body disease cases. This correlates with the finding of Kanaan et al. [10] who found decreased immunoreactivity for tyrosine hydroxylase in MB containing neurons in monkey SN. Here we report that an antibody to the C terminus of optineurin labels MBs. Optineurin (for optic neuropathy inducing protein) came into prominence when mutations in the gene were found to be a cause of adult-onset primary open-angle glaucoma [15]. Later, mutations were found to be a cause of some cases of familial ALS [8, 9, 12]. The protein has been found to interact with huntingtin (htt), transcription factor IIIA [3] and Rab8 [6]. Osawa et al. [14] and Hortobagyi et al. [7] reported a varying extent of optineurin immunoreactivity in cytoplasmic inclusions of Alzheimer disease, Parkinson disease, Creutzfeldt-Jakob disease, multiple system atrophy, and Pick disease. Since mutated optineurin can be a causative factor in some degenerative neurological diseases, and the normal protein can be a significant participant in the pathology of others, the appearance of optineurin in MBs may be a strong signal that they are pathological entities. Several other proteins have been found in association with MBs, among them ataxin-3, which in its mutated form causes spinocerebellar ataxia type 3 [5]. In addition to optineurin, we investigated MBs for the presence of several proteins reported to be associated with other types of intranuclear inclusions, including phosphoTDP-43, phospho-alpha synuclein, huntingtin, fused in sarcoma (FUS), beta tubulin and neurofilament protein. It has been suggested that imbalance between cytoplasmic and nuclear localization of some of these proteins may be part of the pathogenic process by interfering with normal function [18]. We examined the SN of five elderly control cases, five cases with Parkinson’s disease and five cases with Alzheimer’s disease. These cases had previously been found to contain numerous MBs in their SN neurons. Brain tissues were lightly fixed in 4% paraformaldehyde in phosphate buffer. Immunohistochemistry was performed as described previously [16] with the following antibodies: optineurin C-terminal (Cayman #100000, 1:500), ubiquitin (Dako Z0458, 1:1,000 and Zymed, 13-1600, 1:500), phosphorylated C. Schwab (&) S. Yu P. L. McGeer Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada e-mail: claudia.schwab@ubc.ca

Patrick L. McGeer

Papers

The effect of cannabinoids on the number of nuclear membrane-attached ribosomes in infant rat brain.

Reactive Astrocytes Express Acidic Fibroblast Growth Factor in Alzheimer's Disease Brain

P3-288: Beta amyloid deposition in the atrophic form of general paresis

Systems model of cortical organization: Positron emission tomography and neuropsychological test performance

Optineurin is colocalized with ubiquitin in Marinesco bodies