Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

An unusual origin of the celiac trunk and the superior mesenteric artery in the thorax

The authors report a case of a 44‐year‐old male found to have unusual origins of the celiac trunk (CT) and superior mesernteric artrery (SMA) as revealed by routine multidetector computed tomograph (MDCT) angiography. The CT and SMA originate from the thoracic aorta (TA) 21 mm and 9 mm above the aortic hiatus, respectively. The median arcuate ligament (MAL) is located at the level of the L1–L2 intervertebral disc. The course of the CT descends in the thoracic cavity making a 14° acute downward angle in front of the TA; below the level of the MAL, the CT descends, making an angle of 47°. The course of the SMA descends at both the thoracic and abdominal level making an angle of 17°, and having an aortomesenteric distance of 9 mm at the level of the third part of the duodenum. In the present case, the supradiaphragmatic origin of the CT and the SMA was determined by their incomplete caudal descent, associated with a pronounced apparent descent of the diaphragm. A thoracic origin of the CT and SMA and the acute downward aortomesenteric angle (17°) associated with a reduced aortomesenteric distance at the level of the third part of the duodenum (9 mm), although no clinical signs are present, may predispose the patient to develop simultaneously a triple syndrome: the compression of CT by MAL (celiac axis compression syndrome), the compression of SMA by MAL (superior mesenteric artery compression syndrome), and the compression of the duodenum by the SMA (superior mesenteric artery syndrome). Clin. Anat. 26:975–979, 2013. © 2013 Wiley Periodicals, Inc.     

Influence of various irradiation processes on the mechanical properties and polymerisation kinetics of bulk-fill resin based composites

ObjectivesTo assess the effect of irradiation time and distance of the light tip on the micro-mechanical properties and polymerisation kinetics of two bulk-fill resin-based composites at simulated clinically relevant filling depth.MethodsMicro-mechanical properties (Vickers hardness (HV), depth of cure (DOC) and indentation modulus (E)) and polymerisation kinetics (real-time increase of degree of cure (DC)) of two bulk-fill resin-based composites (Tetric EvoCeram^® Bulk Fill, Ivoclar Vivadent and x-tra base, Voco) were assessed at varying depth (0.1–6 mm in 100 μm steps for E and HV and 0.1, 2, 4 and 6 mm for DC), irradiation time (10, 20 or 40 s, Elipar Freelight2) and distances from the light tip (0 and 7 mm). Curing unit's irradiance was monitored in 1 mm steps at distances up to 10 mm away from the light tip on a laboratory-grade spectrometer.ResultsMultivariate analysis (α = 0.05), Student's t-test and Pearson correlation analysis were considered. The influence of material on the measured mechanical properties was significant (η² = 0.080 for E and 0.256 for HV), while the parameters irradiation time, distance from the light tip and depth emphasise a stronger influence on Tetric EvoCeram^® Bulk Fill. The polymerisation kinetics could be described by an exponential sum function, distinguishing between the gel and the glass phase. The above mentioned parameters strongly influenced the start of polymerisation (gel phase), and were of less importance for the glass phase.ConclusionsBoth materials enable at least 4 mm thick increments to be cured in one step under clinically relevant curing conditions.Clinical significanceThe susceptibility to variation in irradiance was material dependent, thus properties measured under clinically simulated curing conditions might vary to a different extent from those measured under ideal curing conditions.     

Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100?mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.     

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease

IntroductionThe inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established.ObjectivesThe study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group.ResultsIn the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= −0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= −0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= −0.41, p=.003).ConclusionsCRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.     

Predicting transmitted irradiance through CAD/CAM resin composite crowns in a simulated clinical model

ObjectiveTo predict the clinically relevant transmitted irradiance that is available for luting when a CAD/CAM restoration is inserted. The influence of irradiance, exposure distance, light curing unit (LCU) angulation and direction of polymerization is analyzed when curing through crowns of different thicknesses.MethodsThree modern CAD/CAM resin-based composites (RBCs) were used to produce 45 crown-shaped specimens. The distance between fissure and crown base was set at 1.0, 1.5 and 2.0 mm (n = 5). Transmitted irradiance, while using a violet-blue LCU, was measured with a photo-spectrometer. 180 exposure conditions per specimen were investigated by variation in LCU curing mode, angulation, exposure distance and direction. Data was analyzed using univariate ANOVA followed by Tukey HSD (α = 0.05) and comparison of 95% confidence intervals.ResultsThe CAD/CAM-RBC’s decadic absorption coefficient ranges from 0.317 mm^?1 to 0.387 mm^?1 and the reflection correcting factor for crowns ranges from 0.305 to 0.337. Transmitted irradiance decreases significantly with increasing exposure distance and decreasing incident irradiance. For tilt angles greater than 10°, transmitted irradiances are significantly reduced (?11% for 20°, ?23% for 30°). Significantly lowest transmitted irradiances were measured for vestibular curing direction (up to ?15%).SignificanceA calculation model can predict the transmitted irradiance through a CAD/CAM restoration in dependence of restoration thickness and radiant emittance. The practitioner can be supported by this model to adapt material choice of dental restoration and adhesive system to the individual situation. Variation in exposure conditions shows negative effect on the transmission of light and should be limited.     

The long-term consequence of salivary contamination at various stages of adhesive application and clinically feasible remedies to decontaminate

Clinical Oral Investigations - To analyse the bond quality in dentine post-ageing after salivary contamination and decontamination at different stages of dental adhesive application. A total of...     

Living donor liver transplantation and hepatitis C

Preliminary results indicate that living donor liver transplantation (LDLT) recipients infected with HCV develop earlier and more severe recurrence than their cadaveric counterparts. The mechanisms underlying this observation are unknown, but could include hepatic regeneration, differences in LDLT recipient demographics, immune homology between donor and recipient, or other factors not previously considered. The optimum clinical approach is to consider LDLT in HCV-infected recipients only as a life-saving procedure and to attempt to eradicate HCV before LT to prevent recurrent infection.     

Advances and perspectives in the genetics of inflammatory bowel diseases.

Several clinical and biological phenotypes define complex diseases such as inflammatory bowel disease (IBD). There is a critical role of the caspase recruitment domain protein 15/nucleotide-binding oligomerization protein 2-dependent (CARD15-NOD2) sensing of bacterial cell wall components in health and disease. The current etiologic model for IBD emphasizes an interaction between susceptibility and modifier genes along with environmental factors. Together, these lead to disease progression. However, further work should clarify the pathophysiological mechanisms leading to IBD and how innate immune signaling confers susceptibility to intestinal inflammation. This is a prerequisite for rational clinical management of IBD. Genetic, functional, serologic testing and development of therapeutics in IBD are discussed.