Marked improvement of left ventricular function after parathyroidectomy in a hemodialysis patient with secondary hyperparathyroidism and left ventricular dysfunction.

A 52-year-old woman, a hemodialysis patient, was admitted because of exertional dyspnea. Echocardiography showed left ventricular (LV) dilatation and reduced contraction. Coronary angiography showed no fixed stenosis. She had elevated levels of parathyroid hormone (PTH) as a result of secondary hyperparathyroidism with advanced renal failure. After parathyroidectomy, marked improvement of LV function following immediate decrease of blood levels of PTH was observed. It is suggested that PTH might have a significant role in the pathogenesis of LV dysfunction and that parathyroidectomy might be effective as a therapy for heart failure in some patients with secondary hyperparathyroidism and LV dysfunction.     

Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis

Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation but also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C-gamma (PLC-gamma) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO), which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus, VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of VEGF.     

Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution

Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca(2+) concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca(2+) overload during the preservation and the activation of Ca(2+) -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.     

NK026680 inhibits T-cell function in an IL-2-dependent manner and prolongs cardiac allograft survival in rats

NK026680 is a triazolopyrimidine derivative that has been shown to inhibit dendritic cell maturation and activation. Here, we examined the immunosuppressive properties of NK026680 on T-cell function and assessed its immunosuppressive efficacy in an ACI (RT1^av1 haplotype) to Lewis (RT1^l) rat heart transplantation model. The effects of NK026680 on T-cell proliferation, activation, and cytokine production were investigated in vitro. Heart transplant recipient rats were administered NK026680 daily for 14 days post-transplantation. In addition to graft survival time, alloimmune responses and graft histology at 4-10 days post-transplantation were assessed. NK026680 was found to inhibit proliferation, CD25 upregulation, IL-2 production, and cell cycle progression in αCD3/αCD28-stimulated murine T cells. These effects were likely due to suppression of the p38 mitogen-activated protein kinase pathway and the subsequent inhibition of p65, c-Fos, and to a lesser extent, c-Jun. Daily NK026680 treatment suppressed alloimmune responses, prevented cellular infiltration into allografts, and prolonged graft survival. The anti-rejection effects of NK026680 were enhanced by tacrolimus. In conclusion, NK026680 inhibits the activation of T cells and prolongs cardiac allograft survival in rats. These features make it a potential candidate immunosuppressant for the treatment of organ transplant patients in the future.     

Effect of death education on self-determination in medical treatment in university students

Background:   Young people have little opportunity to acquire knowledge about or to determine in advance their medical preferences regarding their own end-of-life situation, including diagnosis disclosure and/or organ donation. Therefore a 90 min university-level death education lecture was presented, which was designed to allow students to examine their attitudes regarding medical autonomy and to prepare themselves to make realistic decisions.
Methods:   At the beginning of the semester a survey was conducted using the questionnaire method. Three months later the death education lecture was provided to students in the death education group and the usual lecture to students in the control group, after which the survey using the same questionnaire was readministered. The questionnaire consisted of Templer's death anxiety scale (DAS), five items regarding medical autonomy, background data, and voluntary comment.
Results:   Regarding the DAS and the items on medical autonomy, no significant differences were detected between the pre-test and post-test results, nor between the death education group ( n  = 62) and the control group ( n  = 49). However, in the death education group there was a significant increase in the number writing about the deaths of significant others and in the number providing voluntary comments.
Conclusion:   The death education lecture had the effect of deepening the students' thoughts regarding their own death and/or their attitudes to medical autonomy.     

Anti-hepatitis C virus immunoglobulin M antibody in patients with chronic hepatitis type C.

Anti-hepatitis C virus immunoglobulin M antibody titers were measured by enzyme-linked immunosorbent assay in 28 patients with chronic hepatitis C. Nine patients were treated with alpha-interferon at a dosage of 3 MIU/day for 4 weeks. Anti-HCV IgM was positive in 12 of the 28 patients, and these 12 patients also had significantly higher anti-HCV antibody titers than those patients who were negative for anti-HCV IgM. Among the 9 patients treated with alpha-interferon, anti-HCV IgM positivity was significantly lower in 4 good responders than in 2 non-responders and 3 transient responders at 12 months after the completion of treatment (p < 0.01). These results suggest that anti-HCV IgM titers might be useful for monitoring the antiviral effect of interferon treatment in CH C.