Cigarette smoke-induced alterations in endothelial nitric oxide synthase phosphorylation: role of protein kinase C.

Endothelial nitric oxide synthase (eNOS) is regulated by phosphorylation of Ser(1177) and Thr(495), which affects NO bioavailability. Cigarette smoke disturbs the eNOS-cGMP-NO pathway and causes decreased NO production. Here the authors investigated the acute effects of cigarette smoke on eNOS phosphorylation, focusing on protein kinases (PKs). Endothelial cell culture was concentration- and time-dependently treated first with cigarette smoke buffer (CSB), then with reduced glutathione (GSH) or various PK inhibitors (H-89, LY-294002, Ro-318425, and ruboxistaurin). eNOS, phospho-Ser(1177)-eNOS, phospho-Thr(495)-eNOS, Akt(PKB), and phospho-Akt protein levels were determined by Western blot. CSB increased the phosphorylation of eNOS at Ser(1177) and more at Thr(495) in a concentration- and time-dependent manner (p < .01, p < .05 versus control, respectively) and resulted in the dissociation of the active dimeric form of eNOS (p < .05). GSH decreased the phosphorylation of eNOS at both sites (p < .05 versus CSB without GSH) and prevented the decrease of dimer eNOS level. CSB treatment also decreased the level of phospho-Ser(473)-Akt (p < .05 versus control). Inhibition of PKA by H-89 did not affect CSB-induced phosphorylation, whereas the PKB inhibitor LY-294002 enhanced it at Ser(1117). The PKC blockers Ro-318425 and ruboxistaurin augmented the CSB-induced phosphorylation at Ser(1177) but decreased phosphorylation at Thr(495) (p < .05 versus CSB). Cigarette smoke causes a disruption of the enzymatically active eNOS dimers and shifts the eNOS phosphorylation to an inhibitory state. Both effects might lead to reduced NO bioavailability. The shift of the eNOS phosphorylation pattern to an inhibitory state seems to be independent of the PKA and phosphoinositol 3-kinase (PI3-K)/Akt pathways, whereas PKC appears to play a key role.     

Lung cancer in relation to occupational and environmental chromium exposure and smoking

The increased occurrence of lung cancer in residents of Dolny Kubin, the North-Slovakia district with ferrochromium industry, compared to the general population of Slovakia, led us to the study assessing influence of the occupational and environmantal exposure to chromium on the lung cancer incidence, respecting also the risk coming from cigarette smoking. Residents of Dolny Kubin district with the diagnosed lung cancer in 1984-1999 were involved in the study. The occurrence of lung cancer was significantly higher in people working in ferrochromium industry. The age at the onset of the disease in people exposed to chromium was by 5.5 years lower than in non-exposed. Smoking was an important risk factor, which has been proved particularly in non-exposed group where 62% were smokers and the onset of the lung cancer in them occured about 3.4 years earlier than in non-smokers. In exposed groups, no significant effect of smoking was found. We can conclude, that occupational exposure to chromium was identified as the main risk factor of lung cancer in Dolny Kubin district even overlaying effect of smoking.     

Investigation of perfusion defects by Q-SPECT/CT in patients with mild-to-moderate course of COVID-19 and low clinical probability for pulmonary embolism

Annals of Nuclear Medicine - Pulmonary embolism is a severe source of mortality and morbidity in patients with severe and critical coronavirus disease 2019. It is not yet clear whether the tendency...     

Effect of luting materials,presence of tooth preparation,and functional loading on stress distribution on ceramic laminate veneers: A finite element analysis

Statement of problemHow the polymerization shrinkage, loading, and mechanical properties of luting materials affect the shrinkage and functional stresses in ceramic laminate veneers (CLVs) with and without tooth preparation is unclear.PurposeThe purpose of this finite element analysis (FEA) study was to evaluate the effect of the polymerization shrinkage, functional loading, and mechanical properties of different luting materials on the stresses in ultrathin 0.3-mm CLVs with and without tooth preparation.Material and methodsThree resin cements, RelyX Veneer (RV), Allcem Veneer APS (AV), Variolink Esthetic LC (VE), and 1 flowable composite resin, Tetric N-Flow (TF), were tested for post-gel shrinkage (Shr), Knoop hardness (KHN), elastic modulus (E), compressive strength (CS), and diametral tensile strength (DTS). IPS e.max CAD disks of 0.3-mm thickness were made for simulating the effects of light attenuation. Eight 2-dimensional finite element models (Marc-Mentat) of a maxillary central incisor were generated to evaluate the polymerization shrinkage stress of different materials for luting 0.3-mm CLVs with or without tooth preparation and the stress during functional loading by using a modified von Mises criterion (mvm). Collected data from Shr, KHN, and E were submitted to 2-way ANOVA and the Tukey HSD test (α=.05).ResultsLight attenuation by the 0.3-mm ceramic disk did not significantly affect the E values, but Shr was significantly lower in VE (26%) and TF (35%). TF had lower volumetric Shr (%) when interposing a ceramic disk (0.31%). Both tested tooth preparation options showed similar stress distributions from polymerization shrinkage or functional loading, with higher stress concentration on the incisal edge and also on the cervical surface. The model featuring tooth preparation and RV resin cement had the highest and VE the lowest stress levels.ConclusionsThe flowable composite resin had similar mechanical properties as the resin cements. The stress distribution from shrinkage and functional loading was similar for both techniques with or without tooth preparation.     

Bioactive glass-ceramics in facial skeleton contouring

The removal of certain facial-bone defects is a prerequisite to restoration of function, stability, and appearance. Synthetic bone substitutes are beneficial in cases where other operative techniques would be an unacceptable burden for a patient. Satisfactory results can be achieved in one surgical intervention with low costs and low demand on technical equipment. Osteoconductive, biocompatible, non-resorbable glass-ceramic implants based on oxyfluoroapatite and wollastonite permit osteointegration—a direct physical and chemical bond between live bone tissue and the implant without formation of a fibrous capsule. They display better stress durability in simulated body fluid than hydroxyapatite implants do. This material was used for facial skeletal framework, contour restoration in 44 cases under conditions where other solutions were doubtful. Patients were observed for 24.8 months. Immediate healing occurred without any adverse reaction. The main problem was extrusion, observed in 20.45% cases over a 2–3 month period after the implantation. All cases, with one exception, were solved with a satisfactory final result by reoperation, implant size reduction, and increased soft tissue cover. This approach was found to be a suitable technique, especially for patients exhausted by prior incompetent treatment but still dissatisfied with their appearance. Successful reconstruction with a bone substitute may remarkably increase quality of life for affected persons and, at the same time, reduce surgery-related time and costs.