Upregulation of the cytoskeletal-associated protein Moesin in the neointima of coronary arteries after balloon angioplasty: a new marker of smooth muscle cell migration?

Migrating cells like coronary smooth muscle cells in restenosis change their cell shape and form cellular protrusions called filopodia. A prerequisite for filopodia formation is the rearrangement of the actin cytoskeleton. An essential role of the 78-kDa protein Moesin is described for Rho- and Rac-dependent assembly of actin filaments. In vivo Moesin is not observed in mature smooth muscle cells. The objective of this study was to demonstrate that Moesin is upregulated in migrating coronary smooth muscle cells during restenosis development. In vivo expression of Moesin was upregulated in neointimal coronary smooth muscle cells of dilated porcine coronary arteries compared to the undilated left circumflex coronary artery of the same swine. Concordant to these results Moesin expression was upregulated in migrating and invading human arterial smooth muscle cells in vitro analyzed by FACS, Western blotting and RT-PCR. In addition, the invasive potential of Moesin-positive Mel Im cells transfected with Moesin sense DNA increased by 28% as compared to mock-transfected control, whereas antisense transfected cells had a decreased invasive potential of 32%. Transfection of Moesin-negative HepG2 with Moesin sense cDNA increased the invasive potential by 43%. Finally, transfection of human arterial smooth muscle cells with Moesin sense cDNA caused an increased invasive potential of 30%. Transfection of haSMCs with antisense cDNA decreased the invasive potential by 37% in comparison to mock-transfected control. These results demonstrate for the first time an upregulation of Moesin expression in coronary smooth muscle cells of the neointima after arterial injury. The increased migrative and invasive potential of cells transfected with Moesin confirmed the functional role of Moesin in cell migration. This indicates an important role of Moesin during restenosis development.     

Expression patterns of integrins on quiescent and invasive smooth muscle cells and impact on cell locomotion

Migration and invasion of human arterial smooth muscle cells (haSMCs) are essential steps during the development of atherosclerosis, restenosis, and transplant vasculopathy. The molecular mechanisms leading to these processes are only incompletely understood. Due to their contact to the surrounding extracellular matrix, integrins have been shown to be essentially involved in cell locomotion. Therefore, the function of integrins during this process was analyzed in an in vitro model which was based on the defined quiescent and invasive phenotypes of human haSMCs induced by cell culture conditions. Flow-cytometric analysis of integrin expression between both phenotypes showed a strong upregulation of alpha 5 beta 1 (13.1x) and a modest upregulation of alpha vs beta 3 (3.4x) and alpha IIb (3.0x) in invasive haSMCs in comparison to quiescent ones. Other integrins analyzed (alpha 2, alpha 3, alpha 4, beta 1) did not show differential regulation. Functional inhibition of alpha 5 beta 1 reduced cell migration (-29%+/-8), invasion (-49%+/-16), collagen contraction (-125%), and attachment to fibronectin. Although, there was a clear discrepancy between alpha 5 beta 1 and alpha vs beta 3 expression levels, inhibition of alpha vs beta 3 (-45%+/-9) reduced haSMC invasion equally. Interestingly, alpha vs beta 3 unlike alpha 5 beta 1 blockade caused a significant stimulation of collagen contraction (+52% vs 154%) with possible implications on vascular remodeling. In conclusion, alpha 5 beta 1 blockade or combined alpha 5 beta 1/alpha v beta 3 blockade by specific antibodies or selective RGD peptides together with local drug delivery strategies could be a promising strategy for the therapy of restenotic lesions or atheromatous plaques.     

Treatment of stent restenosis using rotational atherectomy: mechanisms and results

Restenosis after coronary stent implantation remains one of the major limitations of this treatment modality. At present, redilatation is considered the therapeutic option of choice for focal lesions; however, long restenotic lesions (> 10 mm) do not respond favourably. Despite the emerging concept of intracoronary radiation, encouraging acute procedural results are also reported for different debulking techniques (excimer laser angioplasty, directional coronary atherectomy, and rotational atherectomy, or rotablation). Rotablation has been studied most extensively with acute and long-term results published in a total of 500 patients. Experimental and first clinical data indicate favourable results for the rotablator as compared to balloon angioplasty alone for the treatment of in-stent restenosis. Data from the first two randomised clinical trials (ROSTER and A.R.T.I.S.T. trials) have now been published in abstract form, with conflicting results: whereas the monocenter ROSTER trial suggests a clinical benefit to patients treated by the rotablator, the multicenter A.R.T.I.S.T. trial including nearly 300 patients could not prove a benefit for the rotablator as compared to re-dilatation in patients with diffuse stent restenosis. Currently, rotablation for the treatment of restenosis can not be considered as the first line treatment modality in patients with stent restenosis. As a result of unsatisfying angiographic and clinical long-term results by the use of a variety of treatment modalities in diffuse stent restenosis, prevention of this iatrogenic entity will become mandatory.     

薄层扫描法测定熊胆引流物中胆汁酸含量

熊胆向以贵重药材闻名,被称之为稀有药品,为开发熊胆资源,解决熊胆奇缺问题,我校解剖教研室已成功地完成了人工引流熊胆汁技术,可随时进行人工引流获取熊胆汁。为了确定胆汁的质量指标,了解其主要成分,我们进行了引流胆汁与天然熊胆的分析。文献报道,熊胆中主要含熊去氧胆酸(ursodesoxycholic acid,UDCA)、鹅去氧胆酸(cheno desoxycholic acid,CDCA)、胆酸(cholic acid,CA)、去氧胆酸(deoxycholic,acid DCA)等。     

Iwo Jima: 50th anniversary surprise

Retained metal fragments frequently are visualized in x-ray examinations of wounded combat veterans. Retained projectiles (bullets) are seen less often because of surgical removal.     

Development of systemic lupus erythematosus with focal proliferative lupus nephritis during anti-TNF-alpha therapy for psoriatic arthritis]

BACKGROUND: Treatment with tumor necrosis factor-(TNF-)alpha-blocking agents is used in a variety of autoimmune diseases. In anti-TNF-alpha therapy for rheumatoid arthritis, occasionally, the development of autoantibodies as well as lupus-like syndromes have been observed, rarely, glomerulonephritides are also induced. The authors first report the development of lupus erythematosus with renal involvement in a patient with psoriatic arthritis during therapy with the soluble TNF-alpha receptor etanercept. CASE REPORT: A 70-year-old patient with long-standing psoriatic arthritis developed pleuritis, pericarditis, as well as marked arthralgias during therapy with etanercept. Laboratory investigation showed markedly increased parameters of inflammation, antinuclear antibodies (ANA), a proteinuria of 3.2 g/day, mild impairment of renal function, as well as a nephritic urinary sediment. A subsequently performed renal biopsy was diagnostic for focal proliferative lupus nephritis. After withdrawal of etanercept and initiation of a cyclophosphamide pulse therapy in combination with oral steroids, parameters of inflammation and renal function rapidly normalized; pleuritis and pericarditis were not detectable anymore. CONCLUSION: Anti-TNF-alpha therapy in patients with psoriatic arthritis or other autoimmune diseases may lead to induction of systemic lupus with renal involvement.     

Stellenwert der systemische Chemotherapie des Harnblasenkarzinoms

Almost half of the patients with muscle invasive disease already habor at the time of their first diagnosis occult or distant metastases. Systemic disease has a poor prognosis with a long term survival of less than 10%. The administration of systemic chemotherapy aims to improve the course of locally advanced or metastatic disease. A survival benefit of 5% for patients receiving neoadjuvant and 9–11% using adjuvant chemotherapy is in the first scenario minimal, in the adjuvant setting to be noteworthy. The MVAC-schedule and the Gemcitabine/Cisplatin-combination chemotherapy have to be regarded as standard for induction chemotherapy. However, the 5-year survival rates with 15 or 13% are disappointing. Thus, prognostic factors gain importance since with their consideration significant differences in survival rates can be found. Hope is provided by a novel class of substances, the target-specific drugs, which selectively interfere with the cascade of steps involved in tumorigenesis.     

Physiologic assessment of milrinone therapy in severe heart failure patients.

To assess the inotropic, vasodilator, and after-load-reducing effects of intravenous milrinone in patients with severe congestive heart failure, a simple noninvasive echocardiographic study coupled with a right catheterization was performed in 12 patients. Milrinone was administered intravenously as a 50 micrograms.kg-1 bolus followed by a 24-h milrinone infusion at a rate of 0.5 mg.kg-1.min-1 [corrected]. Echocardiographic left ventricular end-diastolic diameter (Ded), end-systolic diameter (Des), and wall thickness were measured at baseline and at 24 h of milrinone infusion, before and after a sublingual nitrate administration (0.8 mg of nitroglycerin) that induced load variations. Hemodynamic measurements were performed simultaneously. Left ventricular end-systolic meridional wall stress (Ses) was then calculated. The slopes of percent fractional shortening (percent FS)/Ses and Ses/Des, obtained during sublingual nitrate administration, were traced. Both end-systolic relations are an index of the contractile state. Milrinone therapy improved hemodynamics in all patients, resulting in stabilized hemodynamic conditions between 12 and 24 h of continuous milrinone infusion. At these times, the cardiac index increased to 30% while the capillary pulmonary wedge pressure and systemic vascular resistance decreased to 26 and 24%, respectively (all p less than 0.01). The average slope of Ses/Des shifted upward from 47.5 +/- 30 to 69.25 +/- 34 (p less than 0.05) and the average slope of (percent FS)/Ses shifted from -0.032 +/- 0.025 to -0.082 +/- 0.061 (p less than 0.01), both variations attesting the inotropic effect of milrinone.(ABSTRACT TRUNCATED AT 250 WORDS)