Age-related impairment of cerebral blood flow response to KATP channel opener in Alzheimer’s disease mice with presenilin-1 mutation

Local cerebral blood flow (CBF) responses to neuronal activity are essential for cognition and impaired CBF responses occur in Alzheimer’s disease (AD). In this study, regional CBF (rCBF) responses to the K_ATP channel opener diazoxide were investigated in 3xTgAD, WT and mutant Presenilin 1(PS1_M146V) mice from three age groups using Laser-Doppler flowmetry. The rCBF response was reduced early in young 3xTgAD mice and almost absent in old 3xTgAD mice, up to 30%–40% reduction with altered CBF velocity and mean arterial pressure versus WT mice. The impaired rCBF response in 3xTgAD mice was associated with progression of AD pathology, characterized by deposition of intracellular and vascular amyloid-β (Aβ) oligomers, senile plaques and tau pathology. The nitric oxide synthase (NOS) inhibitor N^ω-nitro-L-arginine abolished rCBF response to diazoxide suggesting NO was involved in the mediation of vasorelaxation. Levels of phosphor-eNOS (Ser1177) diminished in 3xTgAD brains with age, while the rCBF response to the NO donor sodium nitroprusside remained. In PS1_M146V mice, the rCBF response to dizoxide reduced and high molecular weight Abeta oligomers were increased indicating PS1_M146V contributed to the dysregulation of rCBF response in AD mice. Our study revealed an Aβ oligomer-associated compromise of cerebrovascular function in rCBF response to diazoxide in AD mice with PS1_M146V mutation.     

Effectiveness of Palosuran in Bleomycin-Induced Experimental Scleroderma

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups—group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-β1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-β1 levels (p?<?0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-β1 levels (p?>?0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.     

Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p?<?0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p?=?0.001). Finally, in the 50–125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p?<?0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.     

Adaptation of the Fear of COVID-19 Scale: Its Association with Psychological Distress and Life Satisfaction in Turkey

International Journal of Mental Health and Addiction - The world is currently experiencing a pandemic of an infectious disease called COVID-19 which has drawn global intensive attention. While...     

What might cervical vestibular–evoked myogenic potential abnormalities mean in essential tremor?

Aim/background

Essential tremor (ET) is one of the most common movement disorders. However, its pathogenesis is unclear. Human vestibular reflexes are essential not only for gait and posture but also for goal-directed voluntary movements. In this study, cervical vestibular–evoked myogenic potentials (cVEMPs), the electrophysiological equivalent of the vestibulo-collic reflex was studied in ET patients to understand the interaction between the tremor network and the vestibular neural pathways.

Methods

cVEMPs were recorded in 40 ET patients and 40 age and sex-matched healthy controls (HCs). The latencies of peaks p13 and n23 and peak-to-peak amplitude of p13-n23 were measured.

Results

There was no statistically significant difference between the p13 latencies of the HC and ET groups (p 0.79 and p 0.23 for the right and left sides respectively). n23 latency was shortened bilaterally in the ET group (p 0.009 and p 0.02 for the right and left sides respectively). p13-n23 amplitudes of the ET patients were bilaterally reduced when compared with the HC (p <0.001 and p 0.001 for the right and left sides respectively).

Conclusion

Information provided by vestibular afferents is crucial in the control of voluntary movements in humans. Despite this silent but significant effect, the role of the vestibular system in movement disorders is often overlooked. In this study, it was found that cVEMP responses reflecting the activity of the vestibulo-collic pathway were affected in ET which can be either caused by dysfunctional structures or pathways responsible from ET or an additional disorder of vestibular information processing in these patients.

     

Anatomical variations in branching pattern of arcus aorta: 64-slice CTA appearance

Purpose

To review the 64-slice CTA (computed tomography angiography) appearance of anatomical variations in branching pattern of the arcus aorta, and to determine their prevalence in 1001 cases.

Materials and methods

1001 cases that underwent carotid CTA (performed by a 64-slice scanner) were included in the study.

Results

Seven types of aortic arch were found. In 853 cases (853/1001, 85.2 %) classical branching pattern of arcus aorta (three branches; TB, LCC, LS) was observed. Variations were present in 147 cases (147/1001, 14.7 %). One case (1/1001, 0.1 %) had right aortic arch. The most frequent variation was origination of LCC from TB (arch with 2 branches, TB with LCC and LS) which was observed in 78 cases (78/1001, 7.8 %). Origination of LV directly from the aortic arch (four branches; TB, LCC, LV, LS or TB, LCC, LS, LV) was observed in 51 cases (51/1001, 5.1 %). In two cases (2/1001, 0.2 %) truncus bicaroticus (3 branches; RS, common trunk for carotids, LS) was present. In seven cases (7/1001, 0.7 %) aortic arch had four branches in the order of RCC, RS, LCC and LS. In one case (1/1001, 0.1 %) left truncus brachiocephalicus (three branches; RS, RCC, LTB) was present. Seven cases (7/1001, 0.7 %) had aberrant RS (RCC, LCC, LS, RS).

Conclusion

Variations in branching pattern of arcus aorta are not rare and being aware of them before surgical and interventional procedures of this region is important. CTA can depict the anatomical features of the aortic arch and is valuable as a road map.     

Risk factors for severe and critically ill COVID-19 patients: A review

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1β, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.     

Effects of denture cleaning solutions on the retention of Hader bar clips

Statement of problemThe clinical performance of implant-retained overdentures (IODs) with plastic bar clips made of different materials in the same design and dimensions may vary according to the patient’s daily home care procedures. However, information about the effects of denture cleaning solutions on the retention of Hader bar clips is lacking.PurposeThe purpose of this in vitro study was to evaluate the retention of Hader bar clips made of different polymers after being soaked in denture cleaning solutions.Material and methodsNinety Hader bar clips made of polyamide (PA, n=30), polytetrafluoroethylene (PTFE, n=30), and polyetherketoneketone (PEKK, n=30) materials were tested. Two multiunit abutments were screwed onto the implant analogs and embedded into an acrylic resin block in a standardized position. The digital scanning of the abutments was acquired, and the bar patrix of each material system milled from a cobalt-chromium (Co-Cr) alloy disk by using computer-aided design and computer-aided manufacturing (CAD-CAM). After the milled bar patrices were screwed onto abutments and the metal housings of the bar clips were embedded into acrylic resin blocks, they were connected passively at the same angulation to a universal testing machine. The initial retention values of all Hader bar clips were measured, and each material system was divided into 3 subgroups (n=10) before soaking in the cleaning solutions: distilled water (DW), 5% sodium hypochlorite (NaOCl), or sodium bicarbonate-sodium perborate (SBSP). Each material was soaked for the equivalent of 3 months of clinical use. The final retention values of each Hader bar clip were measured. The data were statistically analyzed by using a 2-way analysis of variance (ANOVA), the Tukey honestly significant difference (HSD) test, and the paired sample t test (α=.05).ResultsThe 2-way ANOVA showed that the denture cleaning solution, the clip material, and their interactions led to significantly different retention values (P<.001). A decrease was observed for the retention values of all test groups after soaking in the cleaning solutions (P<.05). No retention was observed for the PTFE clips after soaking in the 5% NaOCI solution.ConclusionsThe denture cleaning solutions negatively affected the retention of Hader bar clips, regardless of the type of solution and clip material. The 5% NaOCI solution not only decreased the retention of PTFE clips but also completely degraded it. It is recommended that 5% NaOCI solution be avoided for the daily care of IODs with PTFE clips.