Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.     

The prevalence of autoimmune disease in patients with esophageal achalasia

Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10–15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5–19), 8.5 times as likely to have hypothyroidism (95% CI 5.0–14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9–205), 43 times as likely to have systemic lupus erythematosus (95% CI 12–154), and 259 times as likely to have uveitis (95% CI 13–1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5–5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.     

3‐[(2,4‐dimethoxy)benzylidene]‐anabaseine dihydrochloride protects against 6‐hydroxydopamine‐induced parkinsonian neurodegeneration through α7 nicotinic acetylcholine receptor stimulation in rats

To explore a novel therapy against Parkinson's disease through enhancement of α7 nicotinic acetylcholine receptor (nAChR), we evaluated the neuroprotective effects of 3‐[(2,4‐dimethoxy)benzylidene]‐anabaseine dihydrochloride (DMXBA; GTS‐21), a functionally selective α7 nAChR agonist, in a rat 6‐hydroxydopamine (6‐OHDA)‐induced hemiparkinsonian model. Microinjection of 6‐OHDA into the nigrostriatal pathway of rats destroys dopaminergic neurons selectively. DMXBA dose dependently inhibited methamphetamine‐stimulated rotational behavior and dopaminergic neuronal loss induced by 6‐OHDA. The protective effects were abolished by methyllycaconitine citrate salt hydrate, an α7 nAChR antagonist. Immunohistochemical study confirmed abundant α7 nAChR expression in the cytoplasm of dopaminergic neurons. These results indicate that DMXBA prevented 6‐OHDA‐induced dopaminergic neuronal loss through stimulating α7 nAChR in dopaminergic neurons. Injection of 6‐OHDA elevated immunoreactivities to glial markers such as ionized calcium binding adaptor molecule 1, CD68, and glial fibrillary acidic protein in the substantia nigra pars compacta of rats. In contrast, these immunoreactivities were markedly inhibited by comicroinjection of DMXBA. Microglia also expressed α7 nAChR in both resting and activated states. Hence, we hypothesize that DMXBA simultaneously affects microglia and dopaminergic neurons and that both actions lead to dopaminergic neuroprotection. The findings that DMXBA attenuates 6‐OHDA‐induced dopaminergic neurodegeneration and glial activation in a rat model of Parkinson's disease raisethe possibility that DMXBA could be a novel therapeutic compound to prevent Parkinson's disease development. © 2012 Wiley Periodicals, Inc.     

Zigzag gas phases on holey adsorbed layers

We report for the first time a zigzag-shaped gas phase at a highly-ordered pyrolytic graphite/water interface. The novel shape of the gaseous domain is triggered by the holes of the underlying solid-like layers, which are composed of air molecules. Specifically, many holes were created by heating in the thin solid-like layers, which roughened them. The gas domains that formed on these layers deformed from circular to zigzag-shaped as the contact lines expanded while avoiding the holes of the underlying layers. We explained the formation and growth processes of these gas structures in terms of thin film growth, which varies with the mobility of the constituent molecules.

Heating induces the formation of novel zigzag gas phases on the holey adsorbed air layers.     

Clinical features of patients with pars defects identified in adulthood

Purpose

Lumbar spondylolysis is considered a stress fracture of the pars interarticularis that occurs during growth. However, it is sometimes insidious and identified in adults as pseudoarthrosis, the terminal-stage of spondylolysis. The purpose of this study was to identify the clinical features of patients with terminal-stage spondylolysis that first manifested during adulthood.

Patients and methods

Thirty-six patients (21 men, 15 women; mean age 55.8 years; age range 25–77 years) with low back pain (LBP) were studied. In all patients, lumbar spondylolysis had not been diagnosed until the first visit to our hospital. Patient data collected were history of athletic activity and LBP during their growth period and radiological findings, such as spinal level, displacement, and spina bifida occulta (SBO).

Results

Among the 36 patients, including a patient with multi-level spondylolysis (L4 and L5), a total of 37 vertebrae with terminal-stage spondylolysis were identified. Twenty-three (89.2 %) of the 37 vertebrae had L5 spondylolysis. Sixteen patients (44.4 %) had no history of athletic activity, 26 (72.2 %) had no experience of LBP during their growth period, and 14 (38.9 %) had neither. Twenty of the 37 vertebrae (70.4 %) involved displacement (grade 1 = 14; grade 2 = 6). In nine patients (25.0 %; eight men, one woman), SBO of the sacrum was accompanied by L5 spondylolysis.

Conclusions

Approximately 90 % of patients with terminal-stage spondylolysis that was first diagnosed in adulthood involved the L5. Also, about 40 % had no history of athletic activity or experience of LBP during their growth period. In addition, only some patients with L5 spondylolysis had SBO, and all but one of these patients was male. This suggests that male patients with L5 spondylolysis may have some congenital predisposition.