Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by abnormal intracellular Ca2+ handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation-contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca²+ abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) from CPVT1 and CPVT2 patients carrying the RyR2R420Q and CASQ2D307H mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC-CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the [Ca2+]i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC-CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic [Ca2+]i. Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC-CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes.

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On the basis of this study, there is no favorable area for harvesting fat grafts. The donor site can be chosen according to the preference of the surgeon and the patient.

SummaryThe mechanisms underlying the immunomodulatory effects of mesenchymal stem cells (MSCs) have been investigated under extreme conditions of strong T cell activation, which induces the rapid death of activated lymphocytes. The objective of this study was to investigate these mechanisms in the absence of additional polyclonal activation. In co-cultures of peripheral mononuclear blood cells with human MSCs (hereafter referred to as hMSCs), we observed a striking decrease in the level of CD8 expression on CD8+ cells, together with decreased expression of CD28 and CD44, and impaired production of IFN-gamma and Granzyme B. This effect was specific to hMSCs, because it was not observed with several other cell lines. Downregulation of CD8 expression required CD14+ monocytes to be in direct contact with the CD8+ cells, whereas the effects of hMSCs on the CD14+ cells were essentially mediated by soluble factors. The CD14+ monocytes exhibited a tolerogenic pattern when co-cultured with hMSCs, with a clear decrease in CD80 and CD86 co-stimulatory molecules, and an increase in the inhibitory receptors ILT-3 and ILT-4. CD8+ cells that were preconditioned by MSCs had similar effects on monocytes and were able to inhibit lymphocyte proliferation. Injection of hMSCs in humanized NSG mice showed similar trends, in particular decreased levels of CD44 and CD28 in human immune cells. Our study demonstrates a new immunomodulation mechanism of action of hMSCs through the modulation of CD8+ cells towards a non-cytotoxic and/or suppressive phenotype. This mechanism of action has to be taken into account in clinical trials, where it should be beneficial in grafts and autoimmune diseases, but potentially detrimental in malignant diseases.

Applications for intense pulsed light (IPL) for hair removal are gaining favor among other methods, including lasers, because of its noninvasive nature, versatility regarding different skin and hair types, safety, and ease of use. Hair removal using IPL was performed from January 2002 to December 2003 on 108 consecutive patients. Eighty of these patients answered a questionnaire and were enrolled in the study group. The investigated parameters were hair and skin type, number of pulses, fluence, pulse duration, pulse delay, the filters used, and the treated area. The patient assessment of improvement (satisfaction) rate was graded from 1 to 5 points: 1, worse; 2, no improvement; 3, mild improvement; 4, good result; and 5, excellent result. The patients had between 1 and 13 treatments most of them during 2 to 6 sessions. Sixty-seven percent of the patients reported no complications. Prolonged erythema for more than 7 days was reported by 16.25%, blisters by 6.25%, temporary hyperpigmentation by 8.75%, leukotrichia was present in 1 case, and 1 case of persistent hypopigmentation was noted in a young girl. An increased number of complications and a decreased satisfaction rate were noted with higher skin types, but it was not statistically significant. Patients who underwent fewer treatments (1-3 treatments) were more satisfied compared with those who had more than 7 treatments (P < 0.02). Sixty percent of the patients rated their satisfaction to be good to excellent and 65% would ill recommend this treatment to their friends. To minimize the complication rate the authors found that the preset parameters should be adjusted at every treatment session according to the skin response at the previous one. Permanent hair removal cannot be guaranteed and it is not possible to predict the improvement rate. Nevertheless, based on patient satisfaction rate in this study, the authors recommend using IPL for hair removal.