Matrix metalloproteinase and alphavbeta3 integrin-dependent vascular smooth muscle cell invasion through a type I collagen lattice

Smooth muscle cell (SMC) migration from the tunica media to the intima is a key event in the development of atherosclerotic lesions and in restenosis after angioplasty. SMCs require not only migratory but also degradative abilities that enable them to migrate through extracellular matrix proteins, which surround and embed these cells. We used a collagen type I lattice as a coating on top of a porous filter as a matrix barrier in a chamber to test the invasive behavior of SMCs in response to a chemoattractant (invasion assay) and compared that behavior with simple SMC migration through collagen type I-coated filters (migration assay). Inhibitors of matrix metalloproteinase, KB-R8301, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), TIMP-2, and peptide 74, attenuated platelet-derived growth factor-BB (PDGF-BB)-directed SMC invasion across the collagen lattice, whereas no effect was seen with these inhibitors on simple SMC migration through collagen-coated filters. RGD peptide inhibited SMC invasion but did not affect SMC migration. Anti-alphavbeta3 integrin antibody attenuated PDGF-BB-directed SMC invasion, whereas other antibodies against RGD-recognizing integrins, namely alphavbeta5 and alpha5, had no effect. None of these antibodies had any effect on simple SMC migration. RGD peptide and anti-alphavbeta3 antibody inhibited the attachment and spreading of SMCs on denatured collagen but not on native collagen. These findings indicate that there is a difference in the mechanisms between simple SMC migration across a collagen-coated filter and SMC invasion through a fibrillar collagen barrier. A proteolytic process is required for SMC invasion, and the degradation of matrix proteins alters the relationship between matrix protein molecules and SMC surface integrins.     

Change of plasma leukotriene c4 during myocardial ischemia in humans

Changes in leukotriene C4 levels during different degrees of myocardial ischemia in humans were examined by comparing radioimmunoassay measures of leukotriene C4 plasma levels obtained during transient and prolonged myocardial ischemia. Leukotriene C4 levels in systemic arterial and coronary sinus blood were determined in patients with chronic stable angina before and after myocardial ischemia induced either by exercise (supine bicycle ergometer exercise stress testing; n = 14; age, 52 ± 8 years) or by coronary occlusion during angioplasty (n = 14; age 53 ± 7 years). Temporal changes of leukotriene C4 were also followed in arterial and pulmonary artery blood within 24 h after the onset of chest pain (acute phase), and 1 day, 1 week, and 1 month later in 22 patients with acute myocardial infarction (AMI) (12 patients with thrombolytic therapy, age 61 ± 10 years; 10 patients without thrombolytic therapy, age 60 ± 11 years). Clinical characteristics, including coronary risk factors and the severity of coronary artery disease, were not significantly different among the groups. Exercise-induced myocardial ischemia and coronary occlusion did not induce any significant leukotriene C4 changes in the chronic stable angina patients, whereas AMI patients had significantly higher plasma leukotriene C4 levels in both arterial and pulmonary artery blood in the acute phase compared with those of chronic stable angina patients (arterial blood, 471 ± 164 pg/ml and 477 ±235 pg/ml vs. 275 ± 254 pg/ml or 240 ± 66 pg/ml, p< 0.05; pulmonary artery blood in AMI, 543 ± 162 pg/ml vs. 234 ± 125 pg/ml or 225 ±64 pg/ml, coronary sinus blood in chronic stable angina, p < 0.05). These results suggest that leukotriene C4 is involved more in prolonged myocardial ischemia than in transient myocardial is chemia, and that leukocyte function might play a significant role in the pathogenesis of patients with AMI.     

Non-medical palliative care and education to improve end-of-life care at geriatric health services facilities: A nationwide questionnaire survey of chief nurses

Background:   Geriatric health services facilities (GHSF) are expected to assume a growing role in caring for the dying elderly. However, research in this area has so far been scant. The purpose of the present study is to reveal the status of non-medical palliative care and staff education aiming at improving and enhancing end-of-life care at GHSF.
Methods:   The subjects were 2876 chief nurses of GHSF. Data was collected through a mailed questionnaire in 2003. The questionnaire covered the following: (i) staff perception of end-of-life care policies; (ii) staff education; and (iii) available non-medical care. To evaluate the factors correlated with end-of-life care policies at GHSF, we divided the facilities into two groups.
Results:   We analyzed the answers collected from 313 facilities with a progressive policy toward end-of-life care (PP group) and 818 with a regressive policy toward it (RP group). It was found that staff training was conducted more frequently among PP facilities. Generally, nurses in the PP facilities were more confident that they could provide comprehensive on-site end-of-life care and grieving support, but did not feel so sure about their ability to provide better end-of-life environments for dying residents and family by organizing outside support from voluntary and/or governmental organizations and religious organization for healing and to pursue appropriately a written follow-up communication with the bereaved family.
Conclusions:   Our results suggest that providing GHSF staff with education about end-of-life issues or setting up collaboration with the outside is an important factor to enhance overall end-of-life care at these facilities.     

Condylar surface CT value in sagittal plane before and after sagittal split ramus osteotomy

Purpose

The purpose of this study was to evaluate the relationship between computed tomography (CT) values of the condylar surface and temporomandibular joint (TMJ) disc position in the sagittal plane before and after sagittal split ramus osteotomy (SSRO) setback surgery, retrospectively.

Materials and methods

The subjects were 75 patients (150 condyles) who underwent bilateral SSRO setback surgery. They were divided into two groups (42 symmetric patients and 33 asymmetric patients). Maximum CT values (pixel values) of five points of the condylar surface and condylar height, length, fossa height, fossa length, and ramus angle in the sagittal plane were measured preoperatively and 1 year postoperatively. Disc position was classified as anterior disc displacement, anterior type, fully covered type, and posterior type, both pre- and postoperatively, using magnetic resonance imaging (MRI).

Results

Postoperative value was significantly higher than preoperative one in CT value of 135° (P = 0.0199) and 180° (0.0363), in the non-deviation side in the asymmetry group. The anterior disc displacement group was significantly larger than those of some other areas pre- and postoperatively in the CT value of 0° point (P < 0.05).

Conclusions

This study suggested that CT value of the posterior site of the condylar surface could change in the non-deviation side in the asymmetry group after 1 year SSRO, and the condyle with anterior displacement showed high CT value at the anterior site of the condyle before and after surgery.

     

Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones

Current guidelines for treating asymptomatic common bile duct stones (CBDS) recommend stone removal, with endoscopic retrograde cholangiopancreatography (ERCP) being the first treatment choice. When deciding on ERCP treatment for asymptomatic CBDS, the risk of ERCP-related complications and outcome of natural history of asymptomatic CBDS should be compared. The incidence rate of ERCP-related complications, particularly of post-ERCP pancreatitis for asymptomatic CBDS, was reportedly higher than that of symptomatic CBDS, increasing the risk of ERCP-related complications for asymptomatic CBDS compared with that previously reported for biliopancreatic diseases. Although studies have reported short- to middle-term outcomes of natural history of asymptomatic CBDS, its long-term natural history is not well known. Till date, there are no prospective studies that determined whether ERCP has a better outcome than no treatment in patients with asymptomatic CBDS or not. No randomized controlled trial has evaluated the risk of early and late ERCP-related complications vs the risk of biliary complications in the wait-and-see approach, suggesting that a change is needed in our perspective on endoscopic treatment for asymptomatic CBDS. Further studies examining long-term complication risks of ERCP and wait-and-see groups for asymptomatic CBDS are warranted to discuss whether routine endoscopic treatment for asymptomatic CBDS is justified or not.