Brain‐dead donor heart conservation with a preservation solution supplemented by a conditioned medium from mesenchymal stem cells improves graft contractility after transplantation

Hearts are usually procured from brain‐dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD‐donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs‐derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon‐catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution‐supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD‐donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and endonuclease G positive cells were increased in the BD‐group compared to sham. Preservation of BD‐donor hearts with CM resulted in a recovery of systolic graft function (dP/dt_max: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase‐independent apoptosis.     

In Vitro Generation of Atrioventricular Heart Valve Neoscaffolds

Tissue engineering of cardiovascular structures represents a novel approach to improve clinical strategies in heart valve disease treatment. The aim of this study was to engineer decellularized atrioventricular heart valve neoscaffolds with an intact ultrastructure and to reseed them with umbilical cord‐derived endothelial cells under physiological conditions in a bioreactor environment. Mitral (n = 38) and tricuspid (n = 36) valves were harvested from 40 hearts of German Landrace swine from a selected abattoir. Decellularization of atrioventricular heart valves was achieved by a detergent‐based cell extraction protocol. Evaluation of the decellularization method was conducted with light microscopy and quantitative analysis of collagen and elastin content. The presence of residual DNA within the decellularized atrioventricular heart valves was determined with spectrophotometric quantification. The described decellularization regime produced full removal of native cells while maintaining the mechanical stability and the quantitative composition of the atrioventricular heart valve neoscaffolds. The surface of the xenogeneic matrix could be successfully reseeded with in vitro‐expanded human umbilical cord‐derived endothelial cells under physiological flow conditions. After complete decellularization with the detergent‐based protocol described here, physiological reseeding of the xenogeneic neoscaffolds resulted in the formation of a confluent layer of human umbilical cord‐derived endothelial cells. These results warrant further research toward the generation of atrioventricular heart valve neoscaffolds on the basis of decellularized xenogeneic tissue.     

Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser

Objective: Postinflammatory hyperpigmentation is a reactive hypermelanosis of the skin that occurs as a consequence of an inflammatory process, such as acne, eczema, drug reactions, burns, chemical peelings, and laser applications. Although topical agents remain to be the first-line treatment of postinflammatory hyperpigmentation, treatment of recalcitrant cases is challenging. The Q-switched ruby laser, the low-dose Q-switched neodymium-doped yttrium aluminum garnet laser, and the fractional 1550nm erbium-doped fiber laser have been reported to improve postinflammatory hyperpigmentation. Design/setting/participants: The authors present a case of refractory postinflammatory hyperpigmentation successfully treated with two sessions of fractional CO₂ laser in a 24-year-old woman with Fitzpatrick skin type III. Results: After two treatment sessions with a one-month interval, the lesion totally cleared without any complications. Conclusion: Although many laser systems, including fractional CO₂ lasers, can cause postinflammatory hyperpigmentation, they also can be very efficacious tools by using conservative laser settings and by providing appropriate post-treatment care in recalcitrant postinflammatory hyperpigmentation treatment.Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis of the skin. It appears as asymptomatic macules or patches that may be different in size and distribution depending on the causative pathology. Characteristically, it occurs as a consequence of an inflammatory process, such as acne, eczema, drug reactions, burns, chemical peelings, and laser applications. Increased amounts of arachidonic acid metabolites, cytokines, inflammatory mediators, and histamine in the inflammatory process may stimulate the melanocytes causing an increase in the melanin synthesis and transfer of pigment to the surrounding keratinocytes. In PIH, there is either excess melanin production or an abnormal distribution of melanin pigment deposited in the epidermis and/or dermis.1Treatment of PIH consists of a variety of medications and procedures. These include topical bleaching agents, such as hydroquinone, azelaic acid, kojic acid, retinoids, vitamin C, chemical peels, laser therapy, and sunscreens.1,2 The Q-switched ruby laser, the low-dose Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, and the fractional 1550nm erbium-doped fiber laser have been reported to improve PIH.1-4 Here, the authors present a case of refractory PIH treated with fractional CO₂ laser.     

Serum M65 as a Biomarker for Metastatic Renal Cell Carcinoma

Introduction/BackgroundEffective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC.Patients and MethodsThirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA.ResultsThe median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03).ConclusionTo the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.     

Importance of TNF-related apoptosis-inducing ligand in pathogenesis of interstitial cystitis

Introduction  

Although interstitial cystitis is an inflammatory disease, its etiopathogenesis is not clearly understood. The objective of the present study is to investigate the distribution of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in bladder biopsy samples of patients diagnosed with interstitial cystitis and the role of TRAIL in the pathogenesis of interstitial cystitis.