Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease

Periodontal disease (PD) and Alzheimer’s disease (AD) are inflammatory conditions affecting the global adult population. In the pathogenesis of PD, subgingival complex bacterial biofilm induces inflammation that leads to connective tissue degradation and alveolar bone resorption around the teeth. In health, junctional epithelium seals the gingiva to the tooth enamel, thus preventing bacteria from entering the gingivae. Chronic PD involves major pathogens (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) which have an immune armoury that can circumvent host’s immune surveillance to create, and maintain an inflammatory mediator rich, and toxic environment to grow and survive. The neurodegenerative condition, AD is characterised by poor memory and specific hallmark proteins; periodontal pathogens are increasingly being linked with this dementing condition. It is therefore becoming important to understand associations of periodontitis with relevance to late-onset AD. The aim of this review is to discuss the relevance of finding the keystone periodontal pathogen P. gingivalis in AD brains and its plausible contribution to the aetiological hypothesis of this dementing condition

Does the Administration of Curcumin, Compared to Placebo, Change Cognitive Function in Adults Older than 40?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of curcumin, versus a placebo, is effective in changing cognitive function. STUDY DESIGN: Review of 3 randomized control trials with blinding in English from 2008 to present. DATA SOURCES: Articles were selected from Cochrane and PubMed databases based on relevance to the selected research question and patient-centered outcomes. OUTCOME(S) MEASURED: The outcome measured is cognitive change, evaluated by mean score changes in the Mini Mental Status Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). RESULTS: Two of the studies demonstrated no change in cognitive function measured with the MMSE (Ringman JM, Frautschy SA, Teng E, et al. Alzheimers Res Ther. 2012;4(5):43. doi: 10.1186/alzrt146. and Baum, L, Lam CW, Cheung SK, et al. J Clin Psychopharmocol. 2008;28(1):110-113. doi: 10.1097/jcp0b013e318160862c), while the third article also did not demonstrate a change in cognitive function, as measured by the MoCA (Rainey-Smith SR, Brown BM, Sohrabi HR, et al. Br J Nutr. 2016;115(12):2106-2113. doi: 10.1017/S0007114516001203). CONCLUSIONS: The studies are unable to demonstrate that curcumin is more effective than placebo in preventing cognitive changes

STAT6 variants associate with relapse of fosinophilic esophagitis in patients receiving long-term proton pump inhibitor therapy

Background & Aims: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. Methods: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. Results: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. Conclusions: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy

胃排出能の高度遅延は、重症心身障害児（者）の上部食道への非酸性逆流を誘発する

久留米大学2017年

Changes in lipid membranes may trigger amyloid toxicity in Alzheimer's disease

Amyloid beta peptides (A\b{eta}), implicated in Alzheimers disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black lipid membrane (BLM) techniques, we demonstrated that these model membranes differ in their nanoscale structure and physical properties, and interact differently with A\b{eta}. Based on our data, we propose a new hypothesis that changes in lipid membrane due to aging and AD may trigger amyloid toxicity through electrostatic mechanisms, similar to the accepted mechanism of antimicrobial peptide action. Understanding the role of the membrane changes as a key activating amyloid toxicity may aid in the development of a new avenue for the prevention and treatment of AD

Clinical Picture of Gastroesophageal Reflux Disease in Children

Gastroesophageal reflux (GER), defined as the passage of gastric contents into the esophagus, is a normal physiologic process occurring several times per day in healthy infants, children, and adults. The majority of GER episodes occur in the postprandial period, last in <3 min, and cause few or no symptoms. Conversely, when the reflux of gastric contents into the esophagus causes troublesome symptoms and/or complications, we talk about “gastroesophageal reflux disease (GERD).” Distinguishing physiologic GER from GERD may often be tricky for clinicians, especially in infants. The typical presentation of GERD includes the following symptoms: recurrent regurgitation, vomiting, weight loss or poor weight gain, excessive crying and irritability in infants, heartburn or chest pain, ruminative behavior, hematemesis, and dysphagia. Besides these esophageal symptoms, there is a set of extra-esophageal symptoms, mainly respiratory, which may occur along with typical symptoms or may represent the only clinical picture of GERD: odynophagia, wheezing, stridor, cough, hoarseness, dental erosions, and apnea/apparent life-threatening events (ALTEs). While infantile GER tends to resolve spontaneously and does not deserve pharmacological treatment, GERD management includes lifestyle changes, pharmacologic therapy, and surgery. Therefore, a proper diagnosis of these two conditions, besides other possible conditions mimicking reflux, is crucial in order to target the treatment, avoiding the overuse of antacid drugs that currently represents a major source of concern

A Window into the Heterogeneity of Human Cerebrospinal Fluid Aβ Peptides

The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (Aβ) peptides leading to the formation of neurotoxic brain Aβ assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβ peptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβ world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating Aβ assemblies, and (3) communication modes for Aβ peptides and their microenvironment targets. Finally, we suggest that Aβ peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function

Do β-Defensins and Other Antimicrobial Peptides Play a Role in Neuroimmune Function and Neurodegeneration?

It is widely accepted that the brain responds to mechanical trauma and development of most neurodegenerative diseases with an inflammatory sequelae that was once thought exclusive to systemic immunity. Mostly cationic peptides, such as the β-defensins, originally assigned an antimicrobial function are now recognized as mediators of both innate and adaptive immunity. Herein supporting evidence is presented for the hypothesis that neuropathological changes associated with chronic disease conditions of the CNS involve abnormal expression and regulatory function of specific antimicrobial peptides. It is also proposed that these alterations exacerbate proinflammatory conditions within the brain that ultimately potentiate the neurodegenerative process

Investigating the Role of Amyloid Beta Peptides in Inflammation and Alzheimer’s Disease Pathogenesis

Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by severe memory decline and cognitive impairments. In AD patients’ brains, aggregates of amyloid beta (Aβ) peptides, called amyloid plaques, are hypothesized to trigger innate immune responses that contribute to AD pathogenesis. Interestingly, recent studies demonstrated that an increased level of Aβ protected the host against pathogen infections. Using Drosophila as a model organism, our preliminary data showed that the loss of the Drosophila APP homolog, APPL, led to immune deficits against parasite infection, and that overexpression of Drosophila Aβ produced an inflammatory phenotype. These findings suggested that Aβ might be required for a successful immune response. Additionally, we produced flies that develop different levels of Aβ aggregation and examine the inflammation responses of these flies during a pathogen infection. We also optimized fly cognition assay to examine the cognitive functions of the Aβ-expressing flies. Our data suggested that there was a correlation between Aβ aggregation and inflammatory responses, and that Aβ-mediated inflammation was associated with cognitive defects. This study helped us to gain a deeper insight on how innate immunity and infection contribute to the development of AD