Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

Constructing osteoarthritis through discourse – a qualitative analysis of six patient information leaflets on osteoarthritis

Background  

Health service policy in the United Kingdom emphasises the importance of self-care by patients with chronic conditions. Written information for patients about their condition is seen as an important aid to help patients look after themselves. From a discourse analysis perspective written texts such as patient information leaflets do not simply describe the reality of a medical condition and its management but by drawing on some sorts of knowledge and evidence rather than others help construct the reality of that condition. This study explored patient information leaflets on osteoarthritis (OA) to see how OA was constructed and to consider the implications for self-care.     

Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

不同针刺深度对前列腺增生症大鼠重量指数的影响及形态学观察

目的与方法 采用深刺和浅刺对丙酸睾酮所致前列增生症（BPH）大鼠模型进行干预，研究其作用殊同。结果 针刺组前列腺，膀胱指数明显小于模型组；形态学观察，针刺组较模型组增生明显减轻，腺上皮呈单层柱状，腺体数目明显减少，间质充血，钙化明显减轻，结缔组织无增生，腺腔内分泌物减少。深刺组好于浅刺组。结论 深刺对实验性BPH大鼠的干预作用好于浅刺方法。     

Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis

Background  

Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure.     

A skin abscess model for teaching incision and drainage procedures

Background  

Skin and soft tissue infections are increasingly prevalent clinical problems, and it is important for health care practitioners to be well trained in how to treat skin abscesses. A realistic model of abscess incision and drainage will allow trainees to learn and practice this basic physician procedure.     

Primary Hemiarthroplasty for Proximal Humeral Fractures in the Elderly: Long-Term Functional Outcome and Social Implications

Abstract Background: Primary shoulder hemiarthroplasty is an established treatment modality for complex fractures of the proximal humerus. Long-term functional outcome is often disappointing. However, little is known about social implications particularly in the elderly. Methods: A single-institution case series of consecutive geriatric patients (age > 70 years) treated with shoulder hemiarthroplasty for complex fractures of the proximal humerus between 1994 and 1997 was analysed. Postoperative morbidity, long-term function, radiological outcome and social implications were evaluated. Results: Seventy-seven patients fulfilled the study criteria. Median age at the time of operation was 80 years (range 70–93 years). Systemic and local postoperative complications were observed in 8% including 2 patients (3%) with revision surgery. Postoperative mortality was 1%. Forty-eight patients (62%) were available for follow-up (median 49 months, range 25–80 months), 22 (29%) died from causes unrelated to hemiarthroplasty before follow-up and 7 patients (9%) did not attend follow-up examination. Median Constant-Murley score was 41 points (range 17–77 points). Long-term results concerning pain were satisfying. The Oxford shoulder score ranged from 14 to 40 (median 30). Forty-one patients (85%) still lived in their original environment and managed their daily life independently despite poor shoulder function. Four patients (8%) lived in a retirement home and 3 (6%) in a nursery home. Eighty percent of our patients were still able to use public transportation, do the daily shopping and wash their whole body by themselves. Conclusion: Most patients managed their daily life independently despite poor shoulder function.