Endothelin-mediated remodeling in aortas of diabetic rats

BACKGROUND: Smooth muscle cells proliferation and extracellular matrix (ECM) protein deposition are key features of diabetic macroangiopathy. In the present study, we have studied the role of endothelin(A) (ET(A)) receptor, the predominant receptor on smooth muscle cells, in diabetes-induced vascular hypertrophy and remodeling. METHODS: Streptozotocin-induced diabetic rats were administrated a selective ET(A) receptor antagonist, TBC3214, for 26 weeks. Following treatment, aortas were harvested and subjected to gene expression and morphometric analyses. We quantified fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) expression as indicators of increased ECM protein synthesis. ET-1, ET-3, transforming growth factor-beta1 (TGF-beta1) and angiotensinogen mRNA levels were measured to elucidate genes involved in FN expression. We have investigated an embryonic splice variant of FN, oncofetal FN, and nonmuscle myosin heavy chain (SMemb) as vascular remodeling indicators. RESULTS: Our results show that diabetes leads to upregulation of FN, PAI-1, ET-1, ET-3, TGF-beta1 and angiotensinogen mRNA levels in association with increased medial thickness. Immunohistochemical analyses revealed concurrent protein level changes. Diabetes also upregulated oncofetal FN and SMemb mRNA levels. Treatment with TBC3214 attenuated the mRNA levels of several genes and prevented increased medial thickness. CONCLUSIONS: These results indicate that diabetes-induced vascular hypertrophy and remodeling is associated with reexpression of embryonic forms of FN and myosin heavy chain. Such changes are ET-dependent and may be mediated via TGF-beta1 and angiotensin.     

Pleural Lavage: A Novel Diagnostic Approach For Diagnosing Exudative Pleural Effusion

Patients with pleural effusions frequently present a diagnostic and therapeutic challenge. The diagnosis is based on the interpretation of the results of thoracentesis or pleural biopsy. When a malignant tumor metastasizes to the pleura, tumor cells can be seeded over the mesothelial surface or in the subserous layer. In the former situation, tumor cells are abundant in pleural fluid, but in the latter, few malignant cells are exfoliated into the pleural cavity, and microscopic deposits may not be visualized at thoracoscopy. Pleural lavage cytologic study at the time of thoracoscopy has not been studied. The purpose of this study was to assess the value of thoracoscopic pleural lavage as an adjuvant in the diagnostic workup of patients with exudative pleural effusions. Fifty patients with exudative pleural effusions were investigated by pleural fluid cytologic findings, Abram's pleural biopsy, thoracoscopy, and pleural lavage cytologic findings. After aspiration of all pleural fluid, 300 mL saline was instilled into the pleural cavity and then recovered for cytologic analysis. The final diagnoses were 32 malignant (64%), 15 tuberculous (30%), and 3 idiopathic (6%) effusions. In the malignant group, thoracoscopic biopsy had the highest yield (94%) followed by lavage cytologic analysis (84%), fluid cytologic analysis (62%), and biopsy with Abram's needle (50%). The sensitivity of combined thoracoscopy and lavage cytologic analysis was 96%. In the patients with tuberculous pleuritis, the yield from the pathologic examination of the biopsy specimen was 93% with thoracoscopy and 60% with the Abrams needle. The diagnostic yield with cytologic analysis on pleural lavage fluid is significantly higher than that on pleural fluid. This is probably because the cells in the lavage fluid are fresher and better preserved than those in the regular pleural fluid, which may have undergone degenerative changes, yielding false-negative results. Pleural lavage cytologic analysis should be performed in patients with suspected malignant pleural effusion who are subjected to diagnostic thoracoscopy, because it may provide additional information to thoracoscopic biopsy. Accepted for publication: 21 November 2000     

Effect of complete sulfation of bile acids on bile formation in rats

The effect of sulfation of common bile acids on the formation of bile was investigated in male rats by infusing them with the sulfate esters of cholic, chenodeoxycholic, deoxycholic, lithocholic or dehydrocholic acid in four step-wise, increasing doses. Each dose was infused for 30 min and bile collected every 10 min. Control studies were performed by using either albumin solution (the bile acid carrier) or corresponding nonsulfated bile acids at concentrations similar to those of the sulfated products. The secretion of sulfated bile acids was slower and less than that of nonsulfated bile acids, demonstrating transport maximum kinetics rather than the secretory rate maximum characteristic of nonsulfated bile acids. Sulfation significantly increased bile salt-independent bile flow and the choleretic potency of the bile acids tested. With the exception of deoxycholic acid, which had a slight stimulatory effect, bile acid sulfation generally prevented a rise in bile acid-dependent phospholipid and cholesterol secretion. In fact, it reduced biliary phospholipid and cholesterol secretion associated with the secretion of endogenous bile acids. These data are in agreement with the physicochemical properties of sulfated bile acids. They indicate that sulfation prevents the cholestatic action of nonsulfated bile acids, perhaps by increasing bile flow via a high choleretic potential and/or by stimulating bile acid-independent bile flow. The effect of sulfated bile acids on the secretion of biliary phospholipids may protect the canalicular membrane from the detergent properties of bile acids and may thus block the cholestasis which results from high, nonsulfated bile acid concentrations.     

Mental distress and job satisfaction in Palestinian nurses exposed to workplace aggression: a cross-sectional study

Background

Nurses who are exposed to workplace aggression from patients, patient relatives, or colleagues are at risk for mental health disorders and job dissatisfaction. The aim of this study was to assess the prevalence of exposure to workplace aggression and the association between mental distress and job satisfaction in nurses working in the Hebron district of the occupied Palestinian territory.

Effects of rapid maxillary expansion on upper airway volume: A three-dimensional cone-beam computed tomography study

Objective:To compare changes in pharyngeal airway volume and minimal cross-sectional area (MCA) between patients undergoing rapid maxillary expansion (RME) and a matched control group and to identify markers for predicting airway changes using cone-beam computed tomography (CBCT).Materials and Methods:Pre- and posttreatment CBCT scans were selected of children who had RME (14 girls and 12 boys; mean age, 12.4 years) along with scans of a control group (matched for chronological age, skeletal age, gender, mandibular inclination) who underwent orthodontic treatment for minor malocclusions without RME. Changes in airway volume and MCA were evaluated using a standardized, previously validated method and analyzed by a mixed-effects linear regression model.Results:Upper airway volume and MCA increased significantly over time for both the RME and matched control groups (P < .01 and P = .05, respectively). Although the RME group showed a greater increase when compared with the matched controls, this difference was not statistically significant. A reduced skeletal age before treatment was a significant marker for a positive effect on the upper airway volume and MCA changes (P < .01).Conclusions:Tooth-borne RME is not associated with a significant change in upper airway volume or MCA in children when compared with controls. The younger the skeletal age before treatment, the more positive the effect on the upper airway changes. The results may prove valuable, especially in RME of young children.     

Müller glial cells inhibit proliferation of retinal endothelial cells via TGF‐β2 and Smad signaling

Neovascularization is a sight‐threatening complication of ischemic proliferative retinopathies. Transforming growth factor (TGF)‐β, a cytokine with multiple functions in the retina, participates in the control of pathological angiogenesis and neovascularization. Retinal glial (Müller) cells produce TGF‐β2 under physiological and post‐ischemic conditions. To characterize glial cell‐derived mediators of angiogenesis regulation in glial‐endothelial interactions in the retina, we co‐cultured primary Müller cells and bovine microvascular retinal endothelial cells (BRECs). Müller cell‐derived TGF‐β2 was bound by the BRECs, which were found to express serine/threonine kinase TGF‐β receptors, and stimulated TGF‐β‐dependent anti‐proliferative signaling pathways. The proliferation of BRECs was attenuated by exogenous TGF‐β2 as well as by the presence of Müller cell culture media. The following intracellular signaling mechanisms were found to be involved in the anti‐angiogenic action of Müller cell‐derived TGF‐β2: (i) binding of TGF‐β2 to BRECs is mediated by the type‐II TGF‐β receptor, leading to (ii) activation and phosphorylation of receptor‐activated Smads; (iii) Müller cell‐derived TGF‐β2 activates Smad2 and Smad3 to (iv) attenuate the phosphorylation state of the MAP kinases, extracellular signal‐regulated kinase (ERK)‐1/‐2. Neutralizing TGF‐β or TGF‐β type‐II receptor or blocking the activation of Smads partially abrogated the effect of Müller cell‐conditioned media on BRECs. Together, our data suggest that Müller cells release TGF‐β2, inhibiting the proliferation of retinal endothelial cells via activation of Smad2/Smad3 and attenuation of ERK signaling. Given the context‐dependent action of TGF‐β2 on angiogenesis, our results may have implications for understanding the pathogenesis of retinal angiopathies, such as diabetic retinopathy, and the anti‐angiogenic role of TGF‐β therein. GLIA 2014;62:1476–1485     

Spatial distribution of human arachnoid trabeculae

Traumatic brain injury (TBI) is a common injury modality affecting a diverse patient population. Axonal injury occurs when the brain experiences excessive deformation as a result of head impact. Previous studies have shown that the arachnoid trabeculae (AT) in the subarachnoid space significantly influence the magnitude and distribution of brain deformation during impact. However, the quantity and spatial distribution of cranial AT in humans is unknown. Quantification of these microstructural features will improve understanding of force transfer during TBI, and may be a valuable dataset for microneurosurgical procedures. In this study, we quantify the spatial distribution of cranial AT in seven post-mortem human subjects. Optical coherence tomography (OCT) was used to conduct in situ imaging of AT microstructure across the surface of the human brain. OCT images were segmented to quantify the relative amounts of trabecular structures through a volume fraction (VF) measurement. The average VF for each brain ranged from 22.0% to 29.2%. Across all brains, there was a positive spatial correlation, with VF significantly greater by 12% near the superior aspect of the brain (p < .005), and significantly greater by 5%−10% in the frontal lobes (p < .005). These findings suggest that the distribution of AT between the brain and skull is heterogeneous, region-dependent, and likely contributes to brain deformation patterns. This study is the first to image and quantify human AT across the cerebrum and identify region-dependencies. Incorporation of this spatial heterogeneity may improve the accuracy of computational models of human TBI and enhance understanding of brain dynamics.     

Knowledge,attitudes and practices regarding COVID-19 among dental health care professionals: a cross-sectional study in Saudi Arabia

ObjectivesWith the increasing severity of the coronavirus disease (COVID-19) pandemic, it is essential that dental health care professionals (DHCPs) are prepared. The study aim was to assess the knowledge, attitudes and practices (KAP) regarding COVID-19 among DHCPs in Saudi Arabia.MethodsA cross-sectional study using a web-based survey was conducted. A validated and reliable questionnaire was developed that comprised 44 questions. Using Qualtrics survey software, DHCPs working in different settings were approached across five geographical regions of Saudi Arabia.ResultsA total of 318 respondents voluntarily participated in the survey. Most DHCPs showed a moderate level of knowledge (51.6%), a positive attitude (92.1%) and adequate practice standards (86.5%). We found that 94.7% of DHCPs had an adequate overall level of KAP. DHCPs with a doctorate significantly outscored DHCPs with other educational levels with respect to knowledge and practice. Older (51–60 years) DHCPs reported significantly more knowledge than younger DHCPs.ConclusionDHCPs displayed an average level of knowledge that needs to be enhanced through continuing education programmes. However, they showed a positive attitude and an acceptable level of practice, as they were abiding by guidelines issued from various international and national health agencies.