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.

Immunohistochemical studies suggested the existence of a chronic inflammatory condition in affected regions of the brain in Alzheimer disease (AD). Since inflammation can be damaging to host tissue, it was hypothesized that antiinflammatory drugs might inhibit both the onset and the progression of AD. This hypothesis is supported by a number of epidemiological studies suggesting that the prevalence of AD in persons is reduced by 40 - 50% in persons using antiinflammatory drugs. In one small pilot trial in early AD, the nonsteroidal antiinflammatory drug indomethacin appeared to halt the progressive memory loss. Immunohistochemical and molecular biological studies on immune system components in AD brain are revealing the complexities of the innate immune reaction. This very complexity may offer points of therapeutic intervention for new types of antiinflammatory agents. The complement system, microglia and cytokines are key components. This review summarizes the present state of knowledge on the immune system elements found in AD brain.

Brain Inflammation in Alzheimer Disease and the Therapeutic Implications

TOTHE EDITOR: Pick's disease is a progressiveand fatal dementia for which there is no known treatment. Although its prevalence is much lower than that of Alzheimer'sdisease,it alwaysshouldbe includedin a differential diagnosis when Alzheimer's is suspected. Because of the sharp demarcationlines separatingatrophiedportionsof the frontal and temporal lobes from the rest of the brain, Pick's disease can be readily diagnosed premortemthroughcomputed axial tomography,single photon emissioncomputertomography, or positionemissiontomography. Pick's and Alzheimer's diseases have neuropathologic similarities. These include neurofibrillary tangles, accumulations of beta-amyloid precursorprotein,and an apparentchronicinflammatory response. There is activation of severalcomponentsof the classicalcomplementpathway of the immunesystem,includingthe membraneattackcomplex (MAC), and upregulation of 3 of its inhibiting proteins: c1usterin, vitronectin, and protectin.' A somewhat similar distributionof the MAC and 3 of its inhibiting proteins' has been found in Alzheimer's. An autodestructive processhas been hypothesized to accountfor the presenceof the MACJ The apparentrelationship of the pathologyof Pick's and Alzheimer's diseases suggests that drugs therapeutically and prophylacticallyeffectiveagainstAlzheimer'salso mightbe efficacious againstPick's disease. On the basisof the inflammatory pathologyevident in Alzheimer's,nonsteroidalantiinflammatory drugs (NSAIDs)were consideredfor therapy of Alzheimer's.' Indomethacin, an NSAID that crosses the blood-brain barrier rapidly and efficiently,was chosen for a pilot study. Indomethacin proved effective in arresting the progression'of Alzheimer's in a 6month,double-blind, placebo-controlled clinical trial,' stronglysupporting the earlier hypothesis. Further,a cotwin study by Breitneret al. suggested that NSAIDs or steroids might be effective in preventing or delayingthe onsetof Alzheimer'sdisease/ Thus, it is reasonableto propose that administration of antiinflammatory drugs may be of therapeutic use in the treatmentof or may delay the onsetof Pick's disease.Steroids,however,are notoriousfor causingrnajor.Jife-threateningadverse effects, for which there is no remedy.They are, therefore, deemed inappropriatefor the purposes described herein. NSAIDsalso have adverseeffects,the most seriousof which is gastrointestinal ulceration. However, protection against this effect is possible with misoprostol or other gastroprotective agents.The infrequentoccurrence of Pick's disease precludes the organizationof controlledclinical trials comparable with those carried out for Alzheimer's disease. Information,at least initially, is most likelyto be gainedfrom physicians who are treatingpatientsusing the same methodsused to treatAlzheimer's.\

Pick's disease: possible new directions in prophylaxis and therapy:

A reduction in cortical choline acetyltransferase is one of the most widely demonstrated biochemical effects in Alzheimer’s disease (AD)1. Acetylcholinesterase (AChE), the degrading enzyme for acetylcholine, is also reduced2. By application of a sensitive method for AChE-histochemistry we have recently demonstrated a strong association of AChE-positive axons with senile plaques3.

Acetylcholinesterase Histochemical Changes in the Cerebral Cortex of Alzheimer’s Disease

Reply from the Authors: We are pleased that Chen and Craig agree, at least in general terms, with the conclusions of our article. For more than 40 years, NIH-funded groups have been pursuing environmental factors as a cause of Guamanian ALS/PDC with no positive results. Our results suggest that a radical change should be made in ALS/PDC research to one of systematic screening of the genome in affected Chamorro kindreds. Chen and Craig referred, as did we, to early evidence of aggregation in certain Chamorro families. They explain why this compelling evidence was not pursued:"extensive genetic studies …

Patrick L. McGeer

Papers

Brain Inflammation in Alzheimer Disease and the Therapeutic Implications

Pick's disease: possible new directions in prophylaxis and therapy:

Acetylcholinesterase Histochemical Changes in the Cerebral Cortex of Alzheimer’s Disease

Familial nature and continuing morbidity of the ALS-PDC of Guam