Combined with a high-cholesterol diet, endothelial injury of iliac arteries induced arterial occlusive disease in the downstream vessels and consequent bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor overactivity manifested as an increase in voiding frequency.

Oxidative stress and inflammation may be key factors in the development of bladder overactivity in atherosclerosis-induced chronic bladder ischemia.

Background. Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. The combination of CMV-seronegative transplant recipients with CMV-seropositive transplant donors places recipients at the highest risk of CMV disease. In cases of congenital CMV infection, existing immunity only partially protected mothers from reinfection with a different genotypic strain. The effect of differences in infected CMV strains between CMV-seropositive transplant donors and CMV seropositive transplant recipients on the outcome of transplantation remains unclear.Methods. In this prospective multicenter study, the presence of antibodies against strain-specific glycoprotein H epitopes in 84 CMV-seropositive transplant donor/CMV-seropositive transplant recipient renal transplantation cases were determined, and their relationships to acute transplant rejection, CMV infection, degree of antigenemia, and CMV disease were evaluated.Results. Among the 84 donor/recipient pairs, 45 and 32 had matched and mismatched strain-specific glycoprotein H antibodies, respectively. Acute transplant rejection in the mismatched group was more frequent than it was in the matched group (63% vs. 22%;). CMV disease was also more frequently observed in the P p .005 mismatched group (28% vs. 9%;). The mismatched group had a higher level of antigenemia ( P p .026 P p ). .019Conclusions. Our results illustrate more adverse events in the cases with a CMV-seropositive transplant donor and a CMV-seropositive transplant recipient in which the glycoprotein H antibodies are mismatched, suggesting that reinfection with a different CMV strain results in more complications.

Interferon (IFN)-a is one of the most commonly used agents in immunotherapy for patients with advanced stage renal cell carcinoma. However, because of the drug resistance to IFN-a, its benefits are limited. In this study, we examined whether repression of suppressor of cytokine signaling (SOCS) proteins, which are involved in the IFN-induced signaling pathway, can overcome the IFN resistance of renal cell carcinoma. The effect of IFN-a on SOCS3 expression and cell proliferation was examined using IFN-resistant 786-O and IFN-sensitive ACHN cell lines. The effects of SOCS3-targeted siRNA on 786-O xenografts were determined by SOCS3 expression, morphological observation, and tumor volume. The Although over half of renal cancers are found incidentally due to improved radiological evaluation, a quarter of the patients present with advanced disease, including locally advanced or metastatic RCC.As a therapeutic strategy against RCC, surgery is the standard treatment for localized disease. However, its role in the presence of distant metastases is limited. Furthermore, the role of radiotherapy is also limited to palliation of symptoms, and hormonal treatment and chemotherapy are ineffective. Recently, novel targeted agents have been used for the treatment of advanced RCC.(2,3) Randomized phase III trials of the targeted agents versus interferon (IFN) in patients with metastatic RCC have shown benefits associated with the use of these targeted agents. (2,4,5) In the era of molecular targeted agents, immunotherapy seems to have a minimal role in the management of advanced RCC. However, the combination of immunotherapy with molecular targeted agents is of great interest as a potential first-line therapy. Moreover, IFN-a is still one of the options as a subsequent therapy for progressive disease in the National Comprehensive Cancer Network practice guidelines (http://www.nccn.org/ index.asp). It is possible that improving the sensitivity of RCC against IFN-a would contribute to an improvement in the therapeutic effect against advanced RCC.Interferon-a is one of the most frequently used agents in immunotherapy against metastatic or recurrent RCC. Many reports have indicated that IFN-a therapy improved the survival of RCC patients.(6,7) Although this agent can lead to a complete response, (6,7) and can be used as an alternative in non-responders to targeted therapy, its benefits are limited due to drug resistance. Interferon-a can exert a direct antiproliferative response by modulating the expression of proteins that control cell cycle entry and exit, and cell cycle progression, and can also mediate apoptosis by regulating tumor necrosis factor-induced signaling events.(8) Among the IFN-a signalings, the Janus kinase ⁄ signal transducer and activator of transcription (JAK ⁄ STAT) pathway is one of the most important signal transduction cascades. In this pathway, the suppressor of cytokine signaling (SOCS) protein family is known to act as negative regulators of IFN-a signaling by inhibiting the JAK ⁄ STAT pathway.(9) Eight SO...

ObjectivesTo characterise separately the pharmacological profiles of spontaneous contractions from the mucosa and detrusor layers of the bladder wall and to describe the relationship in mucosa between adenosine triphosphate (ATP) release and spontaneous contractions. Materials and MethodsSpontaneous contractions were measured (36°C) from isolated mucosa or detrusor preparations, and intact (mucosa + detrusor) preparations from guinea-pig bladders. Potential modulators were added to the superfusate. The percentage of smooth muscle was measured in haematoxylin and eosin stained sections. ATP release was measured in superfusate samples from a fixed point above the preparation using a luciferin-luciferase assay. ResultsThe magnitude of spontaneous contractions was in the order intact >mucosa >detrusor. The percentage of smooth muscle was least in mucosa and greatest in detrusor preparations. The pharmacological profiles of spontaneous contractions were different in mucosa and detrusor in response to P2X or P2Y receptor agonists, adenosine and capsaicin. The intact preparations showed responses intermediate to those from mucosa and detrusor preparations. Low extracellular pH generated large changes in detrusor, but not mucosa preparations. The mucosa preparations released ATP in a cyclical manner, followed by variations in spontaneous contractions. ATP release was greater in mucosa compared with detrusor, augmented by carbachol and reversed by the M 2 -selective antagonist, methoctramine. ConclusionsThe different pharmacological profiles of bladder mucosa and detrusor, implies different pathways for contractile activation. Also, the intermediate responses from intact preparations implies functional interaction. The temporal relationship between cyclical variation of ATP release and amplitude of spontaneous contractions is consistent with ATP release controlling spontaneous activity. Carbachol-mediated ATP release was independent of active contractile force.