Nature And Properties Of Soils

Background and Purpose The Canadian Study of Health and Aging (CSHA) was conducted in communities and institutions in 10 Canadian provinces. One objective of the study was to study risk factors for vascular dementia (VaD). Methods This was a population-based case-control study. It included 129 patients clinically diagnosed with VaD with duration of symptoms no more than 3 years and 535 control subjects, frequency matched by age group, study center, and residence in community or institution, who were clinically confirmed to be cognitively normal. Odds ratios (ORs) were calculated using unconditional logistic regression for potential risk factors for VaD. Results Risk of VaD was associated with history of arterial hypertension (OR, 2.08; 95% confidence interval, 1.29 to 3.35). Other significantly elevated ORs were seen for history of alcohol abuse (2.45), history of heart condition (1.71), use of aspirin (3.10), and occupational exposure to pesticides and herbicides (2.60), as well as liquid plastic or rubb...

The Canadian Study of Health and Aging

Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease.

A large body of literature supports the idea that nuclear factor kappa B (NF-kB) signaling contributes to a network hub controlling not only immunity, but also inflammation, cancer, and nervous system function. However, studies on NF-kB activity in mitochondrial function are much more limited and scattered throughout the literature. Upon further thought this is very surprising given the importance and the evolutionary history of both NF-kB and the mitochondrion. Both are ancient in their appearance in our biological record where both contribute substantially to cell survival, cell death, and the regulation of function and/or disease. In this review, an attempt is made to understand how NF-kB activity precisely contributes to mitochondrial function. It is assumed the reader already has an understanding of basic mitochondrial biology. The discussion at times is speculative and lacking in evidence, and perhaps even provocative to some, since NF-kB does not yet have defined mitochondrial targeting sequences for some nuclear-encoded mitochondrial genes and mechanisms of mitochondrial import for NF-kB are not yet entirely understood. However, the overall question is legitimate – What is NF-kB doing in the mitochondrion?

/pdf/what-is-nuclear-factor-kappa-b-nf-kb-doing-in-and-to-the-40sgr225l6.pdf

What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion?

The article discusses advances in osmoregulation and excretion with emphasis on how multicellular animals in different osmotic environments regulate their milieu interieur. Mechanisms of energy transformations in animal osmoregulation are dealt with in biophysical terms with respect to water and ion exchange across biological membranes and coupling of ion and water fluxes across epithelia. The discussion of functions is based on a comparative approach analyzing mechanisms that have evolved in different taxonomic groups at biochemical, cellular and tissue levels and their integration in maintaining whole body water and ion homeostasis. The focus is on recent studies of adaptations and newly discovered mechanisms of acclimatization during transitions of animals between different osmotic environments. Special attention is paid to hypotheses about the diversity of cellular organization of osmoregulatory and excretory organs such as glomerular kidneys, antennal glands, Malpighian tubules and insect gut, gills, integument and intestine, with accounts on experimental approaches and methods applied in the studies. It is demonstrated how knowledge in these areas of comparative physiology has expanded considerably during the last two decades, bridging seminal classical works with studies based on new approaches at all levels of anatomical and functional organization. A number of as yet partially unanswered questions are emphasized, some of which are about how water and solute exchange mechanisms at lower levels are integrated for regulating whole body extracellular water volume and ion homeostasis of animals in their natural habitats. © 2014 American Physiological Society.

Osmoregulation and excretion

BACKGROUND Alzheimer's disease (AD) is a neurodegenerative disorder that affects over 45 million people worldwide. Patients with severe AD require help with daily activities and show severe memory impairment. Currently, donepezil is one of two drugs approved by FDA and Health Canada for the treatment of severe AD (MMSE score <10). It is prescribed as 5 or 10 mg/d and an FDA-approved 23-mg/d dose. METHOD This review will discuss risks and benefits of donepezil at these doses in severe AD. Articles were identified using PubMed using the MeSH terms "donepezil" AND "Alzheimer Disease" AND "severe." Three double-blind, placebo-controlled, randomized studies, one post hoc analysis, and one subgroup analysis were selected. RESULTS Donepezil was found to benefit patients in cognition and global functioning. The most consistent improvement was in severe impairment battery (SIB) scores. However, more patients treated with high dosage of donepezil discontinued their treatment due to various adverse events (AEs). CONCLUSION Clinicians must weigh benefits against adverse events when determining the course of therapy, as recommendations for cholinesterase inhibitors in advanced AD remain unclear and vary with different guidelines.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cns.13035

A review of clinical treatment considerations of donepezil in severe Alzheimer's disease.

Ammonia is known to be a potent neurotoxin that causes severe negative effects on the central nervous system. Excessive ammonia levels have been detected in the brain of patients with neurological disorders such as Alzheimer disease (AD). Therefore, ammonia could be a factor contributing to the progression of AD. In this review, we provide an introduction to the toxicity of ammonia and putative ammonia transport proteins. We also hypothesize how ammonia may be linked to AD. Additionally, we discuss the evidence that support the hypothesis that ammonia is a key factor contributing to AD progression. Lastly, we summarize the old and new experimental evidence that focuses on energy metabolism, mitochondrial function, inflammatory responses, excitatory glutamatergic, and GABAergic neurotransmission, and memory in support of our ammonia-related hypotheses of AD.

/pdf/ammonia-as-a-potential-neurotoxic-factor-in-alzheimer-s-4nbaxqdmkc.pdf

Ammonia as a Potential Neurotoxic Factor in Alzheimer's Disease.

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

Alzheimer's Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia.

The soil-dwelling nematode Caenorhabditis elegans is a bacteriovorous animal, excreting the vast majority of its nitrogenous waste as ammonia (25.3±1.2 µmol gFW−1 day−1) and very little urea (0.21±0.004 µmol gFW−1 day−1). Although these roundworms have been used for decades as genetic model systems, very little is known about their strategy to eliminate the toxic waste product ammonia from their bodies into the environment. The current study provides evidence that ammonia is at least partially excreted via the hypodermis. Starvation reduced the ammonia excretion rates by more than half, whereas mRNA expression levels of the Rhesus protein CeRhr-2, V-type H+-ATPase (subunit A) and Na+/K+-ATPase (α-subunit) decreased correspondingly. Moreover, ammonia excretion rates were enhanced in media buffered to pH 5 and decreased at pH 9.5. Inhibitor experiments, combined with enzyme activity measurements and mRNA expression analyses, further suggested that the excretion mechanism involves the participation of the V-type H+-ATPase, carbonic anhydrase, Na+/K+-ATPase, and a functional microtubule network. These findings indicate that ammonia is excreted, not only by apical ammonia trapping, but also via vesicular transport and exocytosis. Exposure to 1 mmol l−1 NH4Cl caused a 10-fold increase in body ammonia and a tripling of ammonia excretion rates. Gene expression levels of CeRhr-1 and CeRhr-2, V-ATPase and Na+/K+-ATPase also increased significantly in response to 1 mmol l−1 NH4Cl. Importantly, a functional expression analysis showed, for the first time, ammonia transport capabilities for CeRhr-1 in a phylogenetically ancient invertebrate system, identifying these proteins as potential functional precursors to the vertebrate ammonia-transporting Rh-glycoproteins.

/pdf/ammonia-excretion-in-caenorhabditis-elegans-mechanism-and-4xsgq0ruae.pdf

Aida Adlimoghaddam

Papers

A review of clinical treatment considerations of donepezil in severe Alzheimer's disease.

Ammonia as a Potential Neurotoxic Factor in Alzheimer's Disease.

Alzheimer's Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia.

Ammonia excretion in Caenorhabditis elegans : mechanism and evidence of ammonia transport of the Rhesus protein CeRhr-1

Regional hypometabolism in the 3xTg mouse model of Alzheimer's disease.