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.

What do you do to start reading kainic acid as a tool in neurobiology? Searching the book that you love to read first or find an interesting book that will make you want to read? Everybody has difference with their reason of reading a book. Actuary, reading habit must be from earlier. Many people may be love to read, but not a book. It's not fault. Someone will be bored to open the thick book with small words to read. In more, this is the real condition. So do happen probably with this kainic acid as a tool in neurobiology.

Kainic acid as a tool in neurobiology

• Measurements on human brain samples of some enzymes concerned with neurotransmitter synthesis suggest serious losses with age. The most severe loss found was that in striatal tyrosine hydroxylase activity, the rate-controlling enzyme in the synthesis of dopamine. Cell counts in the substantia nigra where this dopaminergic tract originates suggest that the decrease in enzyme activity is partly due to cell loss, but must largely reflect decreased activity of residual cells. It is possible that this loss may account for some of the difficulties in movement seen in aged individuals and that it might be less if pigment formation in these cells could be inhibited.

Aging and Extrapyramidal Function

Dopaminergic neurons of the substantia nigra are particularly vulnerable to oxidative and inflammatory attack. Such processes may play a crucial role in the etiology of Parkinson disease (PD). Since glia are the main generators of these processes, the possibility that PD may be caused by glial dysfunction needs to be considered. This review concentrates on glial reactions in PD. Reactive astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD cases indicating a robust inflammatory state. Glia normally serve neuroprotective roles but, given adverse stimulation, they may contribute to damaging chronic inflammation. Microglia, the phagocytes of brain, may be the main contributors since they can produce large numbers of superoxide anions and other neurotoxins. Their toxicity towards dopaminergic neurons has been demonstrated in tissue culture and various animal models of PD. The MPTP and α-synuclein models are of particular interest. Years after exposure to MPTP, inflammation has been observed in the SN. This has established that an acute insult to the SN can result in a sustained local inflammation. The α-synuclein model indicates that an endogenous protein can induce inflammation, and, when overexpressed, can lead to autosomal dominant PD. Less is known about the role of astrocytes than microglia, but they are known to secrete both inflammatory and anti-inflammatory molecules and may play a role in modulating microglial activity. Oligodendrocytes do not seem to play a role in promoting inflammation although, like neurons, they may be damaged by inflammatory processes. Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches. © 2007 Movement Disorder Society

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mds.21751

Glial reactions in Parkinson's disease

Microglia express many leukocyte surface antigens which are upregulated in such chronic degenerative neurological diseases as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). These surface antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and class II glycoproteins, β2-integrins, and the vitronectin receptor. Ligands for these receptors are also found. They include immunoglobulins, complement proteins of the classical pathway, T lymphocytes of the cytotoxic/suppressor and helper/inducer classes, and vitronectin. T lymphocytes marginate along capillary venules, with some penetrating into the tissue matrix. Immunoglobulins and complement proteins are synthesized locally in brain, although they may also come from the bloodstream if the blood-brain barrier is compromised. The membrane attack complex, which is formed from C5b-9, the terminal components of complement, has been identified in AD and multiple sclerosis brain tissue. In addition, proteins designed to defend against bystander lysis caused by the membrane attack complex, including protectin, C8 binding protein, clusterin, and vitronectin, are associated with damaged neuronal processes in AD. Autodestruction may play a prominent part in these 2 diseases.

Microglia in degenerative neurological disease

C-reactive protein (CRP) and complement are hypothesized to be major mediators of inflammation in atherosclerotic plaques. We used the reverse transcriptase-polymerase chain reaction technique to detect the mRNAs for CRP and the classical complement components C1 to C9 in both normal arterial and plaque tissue, establishing that they can be endogenously generated by arteries. When the CRP mRNA levels of plaque tissue, normal artery, and liver were compared in the same cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher than liver. By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway. By in situ hybridization, we detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and macrophages in the thickened intima of plaques. By immunohistochemistry we showed co-localization of CRP and the membrane attack complex of complement. We also detected up-regulation in plaque tissue of the mRNAs for the macrophage markers CD11b and HLA-DR, as well as their protein products. We showed by immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events.

/pdf/generation-of-c-reactive-protein-and-complement-components-28nyhqejok.pdf

Patrick L. McGeer

Papers

Kainic acid as a tool in neurobiology

Aging and Extrapyramidal Function

Glial reactions in Parkinson's disease

Microglia in degenerative neurological disease

Generation of C-reactive protein and complement components in atherosclerotic plaques.