Regulatory Effect of Connexin 43 on Basal Ca2+ Signaling in Rat Ventricular Myocytes

Background: It has been found that gap junction-associated intracellular Ca 2+ [Ca 2+]i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca 2+ signaling, in particular the basal [Ca 2+] i activities, is unclear. Methods and Results: Global and local Ca 2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs) and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY), respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43) with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca 2+ transients and local Ca 2+ sparks in monolayer NRVMs and Ca 2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP3 butyryloxymethyl ester) and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca 2+ signal and LY uptake by gap uncouplers, whereas blockade of IP 3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca 2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibod

Understanding renal posttransplantation anemia in the pediatric population

Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation

ICAR: endoscopic skull‐base surgery

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Microbubble-Assisted P53, Rb, And P130 Gene Transfer In Combination With Radiation Therapy In Prostate Cancer.

Direct intratumoral (IT) injections of replication incompetent adenovirus expressing p53 and retinoblastoma family members pRb and p130 inhibit cancer growth in immune incompetent animals. Combination treatment of radiation therapy and direct IT injection of adenoviral vectors has been explored by others to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates for targeted delivery of genes administered systemically. Here we show that microbubble (MB) p53, pRB, and p130 gene transfer mediated by US at the tumor site resulted in targeted gene transduction and reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with Ads or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed considerable greater reduction in tumor volume compared to Ad.p130 treated tumors. Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05). These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease

Conservative Treatment of Congenital Clinical Anophthalmia

When a child is born with the absence of one or both eyes, the functional and psychological impacts are profound. It is imperative that the ophthalmologist and ocularist begin promptly to expand the socket, stimulate orbital and eyelid growth, and create an orbital volume, socket size, and eyelid length adequate to allow the wear of a normal-sized ocular prosthesis. The tissues in these young children can expand rapidly. It is also important to avoid any unnecessary surgical procedures that can cause scar tissue to form in the socket. Importantly, the lateral canthus should not be cut, as a normal lateral canthal angle is imperative for good expansion. Many techniques have been described, including implanted expanding hydrogel implants, balloon tissue expanders, and a variety of other surgical techniques. The authors feel that the use of a sequence of gradually enlarging acrylic conformers followed by placement of an adult-sized orbital implant at age 4–5 years gives excellent cosmetic and functional outcomes without exposing young children to the risks of multiple surgeries and general anesthesia, as well as the risks related to repeated exposure to radiation through multiple imaging studies. This chapter summarizes the causes and epidemiology of congenital anophthalmia, different expansion techniques described in the past, and the authors’ recommended management of these challenging patients