Background-Mesenchymal stem cells (MSCs) are bone marrow stromal cells that are in phase 1 clinical studies of cellular cardiomyoplasty. However, the electrophysiological effects of MSC transplantation have not been studied. Although improvement of ventricular function would represent a positive outcome of MSC transplantation, focal application of stem cells has the potential downside of creating inhomogeneities that may predispose the heart to reentrant arrhythmias. In the present study we use an MSC and neonatal rat ventricular myocyte (NRVM) coculture system to investigate potential proarrhythmic consequences of MSC transplantation into the heart. Methods and Results-Human MSCs were cocultured with NRVMs in ratios of 1:99, 1:9, and 1:4 and optically mapped.We found that conduction velocity was decreased in cocultures compared with controls, but action potential duration (APD 80 ) was not affected. Reentrant arrhythmias were induced in 86% of cocultures containing 10% and 20% MSCs (nϭ36) but not in controls (nϭ7) or cocultures containing only 1% MSCs (nϭ4). Immunostaining, Western blot, and dye transfer revealed the presence of functional gap junctions involving MSCs. Conclusions-Our results suggest that mixtures of MSCs and NRVMs can produce an arrhythmogenic substrate. The mechanism of reentry is probably increased tissue heterogeneity resulting from electric coupling of inexcitable MSCs with myocytes.

Metabolic bone diseases are a diverse group of diseases that result in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d) growth. Osteoporosis, the most common metabolic bone disease, results in generalized loss of bone mass and deterioration in the bone microarchitecture. Impaired chondrocyte development and failure to mineralize growth plate cartilage in rickets lead to widened growth plates and frayed metaphyses at sites of greatest growth. Osteomalacia is the result of impaired mineralization of newly formed osteoid, which leads to characteristic Looser zones. Hypophosphatasia is a congenital condition of impaired bone mineralization with wide phenotypic variability. Findings of hyperparathyroidism are the result of bone resorption, most often manifesting as subperiosteal resorption in the hand. Renal osteodystrophy is the collection of skeletal findings observed in patients with chronic renal failure and associated secondary hyperparathyroidism and can include osteopenia, osteosclerosis, and "rugger jersey spine." Hypoparathyroidism is most commonly due to iatrogenic injury, and radiographic findings of hypoparathyroidism reflect an overall increase in bone mass. Thyroid hormone regulates endochondral bone formation; and congenital hypothyroidism, when untreated, leads to delayed bone age and absent, irregular, or fragmented distal femoral and proximal tibial epiphyses. Soft-tissue proliferation of thyroid acropachy is most often observed in the hands and feet. The findings of acromegaly are due to excess growth hormone secretion and therefore proliferation of the bones and soft tissues. Vitamin C deficiency, or scurvy, impairs posttranslational collagen modification, leading to subperiosteal hemorrhage and fractures. RSNA, 2016.

Patients with IFI have increased ischial and femoral neck angles compared with controls. These anatomical variations in pelvic morphology may predispose to IFI. MRI is a useful method of not only assessing the osseous and soft-tissue abnormalities associated with IFI, but also of quantifying anatomical variations in pelvic morphology that can predispose to IFI.

Gabapentin (1-aminomethyl-cyclohexaneacetic acid) is an amino acid that has the structure of the neurotransmitter γ-aminobutyric acid (GABA). It is a novel drug used for the treatment of postoperative pain with antihyperalgesic properties and a unique mechanism of action. Gabapentin and the related, more potent compound pregabalin have been shown to be beneficial in the treatment of neuropathic pain as well as postoperative pain following spinal surgery and hysterectomy. This study reviews five aspects of gabapentin: (1) chemical and structural characteristics; (2) pharmacokinetics and pharmacodynamics; (3) application in acute pain management; (4) adverse effects; and (5) drug safety. Overall, gabapentin has been reported to be a safe and efficacious drug for the treatment of postoperative pain.

Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood. We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase-activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.