Erythromycin suppresses the expression of cyclooxygenase-2 in rheumatoid synovial cells.

OBJECTIVE: To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression. CONCLUSION: Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.

Minimally invasive uncemented total hip arthroplasty through an anterolateral approach with a shorter skin incision.

Total hip arthroplasty using a short skin incision has been associated with great controversy. It has still not yet been demonstrated that a shorter skin incision is efficient or safe for patients. Here, we review 212 cases of uncemented total hip arthroplasty performed since 1999 using the anterolateral approach and a shorter skin incision. Patients were divided into three groups according to the length of the incision at the end of surgery; incisions of 10 cm or less were defined as "mini" ( n = 115) and incisions of 10-15 cm as "short" ( n = 70); these two groups were defined as shorter skin incision groups. Incisions longer than 15 cm in patients undergoing the standard procedure were defined as "conventional" and served as the controls ( n = 27). Statistically significant differences were found with regard to operative duration and intraoperative blood loss: the shorter the length of the incision, the shorter the operative duration and the smaller the intraoperative blood loss. There was no significant difference in postoperative bleeding or in the incidence of complications among the three groups. Total blood losses in the shorter groups were each statistically significant less than that in the conventional group. Comparing the mini group to the short group, the length of the skin incision was influenced by the body mass index (BMI) and gender. For those with a high BMI and for male patients, a slightly longer incision was necessary. We concluded that total hip arthroplasty through a mini or short incision was indeed efficient for patients compared with total hip arthroplasty using a conventional incision.

Progression from calcifying tendinitis to rotator cuff tear.

This report documents the clinical, radiographic and histologic findings in a 46-year-old man with calcifying tendinitis in his left shoulder which progressed to rotator cuff tear. The patient had a 1-year history of repeated calcifying tendinitis before being referred to our hospital. On the initial visit, radiographs and magnetic resonance imaging (MRI) revealed calcium deposition localized in the supraspinatus tendon without apparent tear. Three months after the first visit, MRI revealed a partial-thickness rotator cuff tear at the site of calcium deposition. Surgical and histologic findings demonstrated that calcium deposition was the cause of cuff rupture. To our knowledge, based on a review of the English literature, this is the first case report in which the progression from calcifying tendinitis to rotator cuff tear has been serially observed.

Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells.

The histological grade of chondrosarcoma correlates well with their clinical behavior and with the patient's survival duration. We have previously demonstrated that p21 was expressed in the hypertrophic chondrocytes of the growth plate. To assess the relationship of p21 (waf1/cip1) to cell differentiation in chondrosarcoma, we examined the p21 expression in 14 cases of chondrosarcoma immunohistochemically and the induction of p21 by insulin-like growth factor-I (IGF-I) during cell differentiation in SW1353 chondrosarcoma cells. p21 immunoreactivity was seen in well-differentiated chondrosarcoma cells and was mutually exclusive with MIB1 reactivity in grade-1 chondrosarcoma. In vitro, the proteoglycan synthesis of SW1353 cells was increased by IGF-I in a dose-dependent manner. However, cell proliferation was not markedly stimulated. Overexpressions of p21 mRNA and p21 protein in SW1353 cells were induced by IGF-I 100 ng/ml. Our results suggested that the p21 expression was directly related to tumor differentiation and that the p21 expression was an important mediator for IGF-I in chondrosarcoma cells.

Catalytic Asymmetric Synthesis of Antimalarial Alkaloids Febrifugine and Isofebrifugine and Their Biological Activity.

Antimalarial alkaloids febrifugine (1) and isofebrifugine (2) were efficiently synthesized from simple achiral starting materials on the basis of the catalytic asymmetric synthesis. The first key reaction was performed using the tin(II)-mediated catalytic asymmetric aldol protocol to afford chiral aldehyde 3 in high yield with high diastereo- and enantioselectivities. The second key step, a Mannich-type reaction, did not give satisfactory results according to the conventional methods. We then developed a novel aqueous Mannich-type three-component reaction of an aldehyde, an amine, and a vinyl ether using a Lewis acid-surfactant combined catalyst (LASC), and the key intermediates 16 and 17 were obtained in high yields. The final coupling reactions of bromoacetone 14 with 4-hydroxyquinazoline were carried out using basic conditions, and successive deprotection gave 1 and 2, respectively, without any isomerization. These unambiguous total asymmetric syntheses revealed that the absolute configurations of febrifugine and isofebrifugine were not (2'S,3'R) and (2'R,3'R) as reported previously but (2'R,3'S) and (2'S,3'S), respectively (1' and 2'). Finally, antimalarial activities of the synthesized febrifugine and isofebrifugine, and their antipodes, were examined. It was revealed that the activities and selectivities of natural febrifugine and isofebrifugine were much higher than those of the antipodes.