Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T‐cell cross‐priming

Toll‐like receptor (TLR) ligands are attractive candidate adjuvants for therapeutic cancer vaccines, since TLR signaling stimulates and tunes both humoral and cellular immune responses induced by dendritic cells (DCs). Given that human skin contains a dense network of DCs, which are easily accessible via (intra‐)dermal delivery of vaccines, skin is actively explored as an antitumor vaccination site. Here we used a human skin explant model to explore the potential of TLR ligands as adjuvants for DC activation in their complex microenvironment. We show that topical application of Aldara skin cream, 5% of which comprises the TLR7 agonist imiquimod, significantly enhanced DC migration as compared with that resulting from intradermal injection of the TLR7/8 ligand R848 or the soluble form of imiquimod. Moreover, Aldara‐treated DCs showed highest levels of the costimulatory molecules CD86, CD83, CD40, and CD70. Topical Aldara induced the highest production of pro‐inflammatory cytokines in skin biopsies. When combined with intradermal peptide vaccination, Aldara‐stimulated DCs showed enhanced cross‐presentation of the melanoma antigen MART‐1, which resulted in increased priming and activation of MART‐1‐specific CD8⁺ T cells. These results point to advantageous effects of combining the topical application of Aldara with antitumor peptide vaccination.     

The effects of water immersion and restraint stress on the expressions of apelin,apelin receptor (APJR) and apoptosis rate in the rat heart

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A) + WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A + WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A + WIRS group than that of the control group. Our study showed that WIRS for 6 h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.     

Spontaneous coronary artery dissection as a cause of myocardial infarction

Spontaneous coronary artery dissection (SCAD) is a rare disease that is usually seen in young women in left descending coronary artery and result in events like sudden cardiac death and acute myocardial infarction. A 70-year-old man was admitted to the emergency department with chest pain which started 1 h ago during a relative’s funeral. The initial electrocardiography demonstrated 2 mm ST-segment depression in leads V1-V3 and the patient underwent emergent coronary angiography. SCAD simultaneously in two different coronary arteries [left anterior descending (LAD) artery and left circumflex (LCx)] artery was detected and SCAD in LCx artery was causing total occlusion which resulted in acute myocardial infarction. Successful stenting was performed thereafter for both lesions. In addition to the existence of SCAD simultaneously in two different coronary arteries, the presence of muscular bridge and SCAD together at the same site of the LAD artery was another interesting point which made us report this case.     

Atrial electromechanical coupling intervals in pregnant subjects

Atrial fibrillation (AF), which is the most common cardiac arrhythmia, may cause serious symptoms and impair quality of life.1 The development of AF is associated with many risk factors, including age, male gender, hypertension, heart failure, valvular disease, diabetes mellitus (DM) and left atrial (LA) enlargement.2-4 Electrical and/or mechanical remodelling of the atria is thought to be a pathophysiological characteristic of AF.5The pregnant state may be pro-dysrhythmic. This is related to the cardiovascular, hormonal, haemodynamic and autonomic changes during healthy pregnancy. Levels of oestrogen and β-human chorionic gonadotropin increase dramatically. Haemodynamic changes include an increase in circulating blood volume, which increases cardiac output. This results in myocardial stretch and an increase in cardiac end-diastolic volume. High plasma catecholamine concentrations and adrenergic receptor sensitivity increase sympathetic tone. All these changes in pregnant women may make them more prone to dysrhythmogenesis.6Most pregnant women complain of palpitations, dizziness and even syncope, but these symptoms are rarely associated with cardiac dysrhythmias. AF is the most common clinically significant cardiac arrhythmia in the general population but it is rarely seen in pregnant women. When it occurs, it can represent a benign, self-limited lone episode of AF or may be secondary to congenital or rheumatic valvular disease, hypertrophic cardiomyopathy, thyroid disease, or pre-excitation syndrome.Two simple electrocardiogram (ECG) markers, namely maximum P-wave duration (Pmax) and P-wave dispersion (PD), have been used to evaluate intra- and inter-atrial conduction times and the inhomogeneous propagation of sinus impulses, which are well-known electrophysiological characteristics of the atrium prone to fibrillation.7,8 Prolonged Pmax and PD have been reported to represent an increased risk for AF in patients with no underlying heart disease.7,8 Besides, evidence from laboratory and epidemiological research suggests that systemic inflammation may play a role in AF aetiology.9 It has also been demonstrated that atrial electromechanical coupling, measured by tissue Doppler imaging (TDI), as significantly longer in patients with paroxysmal AF than in control groups.10,11To our knowledge, no study evaluating PD and atrial electromechanical coupling has been investigated in pregnant subjects without additional systemic disease. Therefore, in this study we aimed to examine atrial electromechanical coupling and PD, reflecting inter-atrial conduction times in pregnant subjects.     

Fracture resistance of roots filled with three different obturation techniques

Objectives: The aim of this study was to compare in vitro root fracture resistance following root canal filling with AH 26 using lateral condensation, BeeFill, and Thermafil techniques. Study Design: Eighty extracted human mandibular premolars with similar dimensions were selected. In order to standardize the roots, measurements were taken in two separate regions of the teeth—at the cemento-enamel junction and 8 mm apically from the junction—buccolingual as well as mesiodistal for every tooth. Teeth were then randomly divided into five groups (n=16). With the exception of the non-prepared group (Group 1), instrumentation was done in all groups. In group 2, instrumentation but no filling was performed; in group 3, the obturation was done with AH 26 + gutta-percha; in group 4, with AH 26 + BeeFill and in group 5, AH 26 + a Thermafil obturator was used. All the roots were mounted vertically in copper rings and filled with acrylic resin, exposing 8 mm of the coronal part. A universal testing machine was used for the strength test. Results: The results were analyzed using the one-way ANOVA test. The significance between the groups was tested with Temhane’s T2 test. The results indicate that instrumentation of root canals had a significant effect on fracture resistance (p<0.05). In addition, there were no differences between the root canal obturation techniques; furthermore, these techniques did not create a statistically important resistance to vertical fracture (p>0.05). Conclusions: The results suggest that instrumentation of root canals significantly weakens the tooth structure to fracture and the root canal obturation techniques that are used are not able to form reinforcement. Key words:AH 26, obturation technique, vertical fracture.     

Minimal intervention concept: a new paradigm for operative dentistry

The current treatment philosophy is to prevent and detect dental disease at the earliest stage in order to avoid invasive treatment. With the current understanding of the nature of dental disease and its process, the treatment philosophy is now changing to a more conservative approach and the concept of minimal intervention is gaining popularity in modern dentistry throughout the world. It is now established that demineralized but non-cavitated enamel and dentine can be healed and traditional surgical approach of drilling and filling may no longer be necessary as this only treats the symptoms of the disease and not the cause. However, when surgical intervention is indicated, the least invasive techniques such as preventive resin restoration and minimal cavity preparation are utilized. The aim of this article is to give dental professionals an overview of the concepts of minimal intervention dentistry and recent innovations in dental technology in both the diagnosis and treatment of dental caries.     

Increased carotid intima-media thickness is associated with higher SYNTAX score

The main purpose of this study was to investigate the relation between carotid intima-media thickness (CIMT) and coronary artery disease (CAD) complexity. Consecutive patients (n = 360) with CAD confirmed by coronary angiography were enrolled. Mean CIMT and the overall SYNTAX score (SXscore) were 0.87 ± 0.12 mm and 15 ± 9, respectively. In univariate analysis, there was a significant correlation between the overall SXscore and CIMT (r = .42, P < .001), age (r = .23, P < .001), hypertension (r = .27, P = 0.001), diabetes (r = 0.11, P = 0.02), smoking (r = .24, P = .01), dyslipidemia (r = .2, P = 0.03), and β-blocker use (r = .19, P < .001). In multivariate analysis, CIMT (β = .34, P < .001) and age (β = .11, P < .019) were independently associated with SXscore. We have demonstrated a significant relation between CIMT and SXscore. Although this study is correlative and no causative conclusions can be drawn, our findings suggest that increased CIMT could reflect complex coronary artery lesions.