Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation.

OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-ß) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-ß signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-ß expression and Smad2/3 following TGF-ß phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-ß expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.

Controlling joint instability delays the degeneration of articular cartilage in a rat model.

OBJECTIVE: Joint instability induced by anterior cruciate ligament (ACL) transection is commonly considered as a predisposing factor for osteoarthritis (OA) of the knee; however, the influence of re-stabilization on the protection of articular cartilage is unclear. The aim of this study was to evaluate the effect of joint re-stabilization on articular cartilage using an instability and re-stabilization ACL transection model. DESIGN: To induce different models of joint instability, our laboratory created a controlled abnormal joint movement (CAJM) group and an anterior cruciate ligament transection group (ACL-T). Seventy-five Wistar male rats were randomly assigned to the CAJM (n = 30), ACL-T (n = 30), or no treatment (INTACT) group (n = 15). Cartilage changes were assessed with soft X-ray analysis, histological and immunohistochemistry analysis, and real-time polymerase chain reaction (PCR) analysis at 2, 4, and 12 weeks. RESULTS: Joint instability, as indicated by the difference in anterior displacement between the CAJM and ACL-T groups (P < 0.001), and cartilage degeneration, as evaluated according to the Osteoarthritis Research Society International (OARSI) score, were significantly higher in the ACL-T group than the CAJM group at 12 weeks (P < 0.001). Moreover, joint re-stabilization maintained cartilage structure (thickness [P < 0.001], surface roughness [P < 0.001], and glycosaminoglycan stainability [P < 0.001]) and suppressed tumor necrosis factor-alpha (TNF-α) and caspase-3 at 4 weeks after surgery. CONCLUSION: Re-stabilization of joint instability may suppress inflammatory cytokines, thereby delaying the progression of OA. Joint instability is a substantial contributor to cartilage degeneration.

Multiple dural arteriovenous fistulae involving the cavernous and sphenoparietal sinuses.

A 72-year-old woman who presented with a unilateral oculomotor nerve palsy was shown to have a very rare condition: multiple dural arteriovenous fistulae (DAVF) involving the cavernous and sphenoparietal sinuses. The sphenoparietal DAVF was cured completely by transarterial embolisation. Symptomatic relief was accomplished by this procedure. The cavernous sinus DAVF progressed to acquire cortical venous drainage, and was obliterated completely by transvenous embolisation.

Relationship between plasma levels of vascular endothelial growth factor and serum levels of interleukin-12 in patients with colorectal cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) is thought to be the most potent angiogenic factor in the numerous malignant tumors and a prognostic indicator for cancer patients. Interleukin 12 (IL-12) is a heterodimeric cytokine that has potent anti-tumor and anti-metastatic activities. Recently, it has been suggested that IL-12 regulates VEGF in a murine breast cancer model. MATERIALS AND METHODS: Blood from 26 patients with colorectal cancer was obtained prior to surgery. Plasma levels of VEGF and serum levels of IL-12 were assessed using the quantitative sandwich enzyme immunoassay technique. We investigated the preoperative relationships between plasma levels of VEGF, serum levels of IL-12 and clinicopathological factors in patients with colorectal cancer. RESULTS: Although not statistically significantly, high plasma levels of VEGF and low serum levels of IL-12 tended to occur with more advanced colorectal cancer. Plasma levels of VEGF in patients who had circumferential involvement of the tumor greater than 1/2 were only significantly increased. The preoperative relationship between plasma levels of VEGF and serum levels of IL-12 tended to be negatively correlated. CONCLUSION: These results suggest that high plasma levels of IL-12 or low serum levels of IL-12 may be observed in more advanced colorectal cancer patients. Thus, these patients may require additional immunochemotherapy after surgery. IL-12 may regulate VEGF in the patients diagnosed with colorectal cancer.

Ruthenium-catalyzed cyclic carbonylation of allenyl alcohols. Selective synthesis of gamma- and delta-lactones

[reaction: see text] Ruthenium complex-catalyzed carbonylation of allenyl alcohols quantitatively gave cyclic carbonyl compounds, gamma- and delta-lactones, in which the hydroxy group of allenyl alcohols participated in the cyclization. A wide variety of allenyl alcohols, such as mono-, di-, and trisubstituted alcohols, can be used in this reaction to produce 3- and 4-substituted gamma-lactones. Similarly, the cyclic carbonylation of 3,4-pentadien-1-ol 10a and 2-methyl-4,5-hexadien-2-ol 11a gave delta-lactones, 5,6-dihydro-3-methyl-2H-pyran-2-one 10b, and 5,6-dihydro-6,6-dimethyl-3-methyl-2H-pyran. 2-one 11b, respectively, in a quantitative yield.

Serum levels of interleukin-12 in patients with gastrointestinal cancer.

Interleukin 12(IL-12) is a heterodimeric cytokine that has potent anti-tumor and anti-metastatic activities. Although clinical trials of recombinant human IL-12 have begun in patients with several advanced malignancies, very few studies have investigated the preoperative serum levels of IL-12 in patients with gastric or colorectal cancer. The purpose of the present study was to investigate the relationships between the preoperative serum levels of IL-12 and clinicopathological factors in patients with gastric or colorectal cancer. Blood was obtained before surgery from 14 patients with gastric cancer and 15 patients with colorectal cancer. Serum levels of IL-12 was assessed using the quantitative sandwich enzyme immunoassay technique. Although not statistically significantly, low serum levels of IL-12 tended to be associated with gastric cancer patients who were node-positive, CEA positive, had tumors that penetrated the serosa, had tumors greater than 5 cm in diameter, were more than 60 years-old, or were more advanced than stage IIIA(TNM) or stage IIIa(Japanese Research Society for Gastric Cancer). Patients with colorectal cancer who were node-positive, had tumors that penetrated the serosa, were more than 60 years-old, or were more advanced than stage III(TNM), stage IIIa(Japanese Society for Cancer of the Colon and Rectum) and Dukes' C also tended to have low serum IL-12 levels. These results suggest that low serum levels of IL-12 may be observed in more advanced gastric and colorectal cancer patients. Thus, patients with low serum levels of IL-12 in gastric or colorectal cancer may require additional immunochemotherapy after surgery.

Screw-sense-selective polymerization of aryl isocyanides initiated by a Pd-Pt mu-ethynediyl dinuclear complex: a novel method for the synthesis of single-handed helical poly(isocyanide)s with the block copolymerization technique

Living polymerization of chiral aryl isocyanides, such as m- and p-menthoxycarbonylphenyl isocyanides 2 and 5, initiated by the Pd-Pt mu-ethynediyl dinuclear complex 1, proceeds with a high screw-sense selectivity to give the poly(isocyanide)s 3 and 6, which exhibit a large specific rotation and an intense CD band at lambda = 364 nm as a consequence of a helical chirality. The molar optical rotation and molar circular dichroism of the resulting polymers 3 and 6 reach a constant value at a degree of polymerization (Pn) of more than 30. Screw-sense-selective polymerization of achiral aryl isocyanides that bear very bulky substituents, such as 3,5-di(propoxycarbonyl)phenyl isocyanide (11), 3,5-di(butoxycarbonyl)phenyl isocyanide (13), and 3,5-di(cyclohexyloxycarbonyl)phenyl isocyanide (15), is achieved by the use of chiral oligomer complexes 3(30) and 6(30), prepared from the reaction of 1 with 30 equivalents of 2 or 5, as an initiator to give predominantly single-handed helical polymers. In contrast, smaller aryl isocyanides are also polymerized by 3(30) and 6(30) with screw-sense selectivity in the initial stage of the reaction, but the single-handed helix is not preserved up to high molecular weight. Kinetic studies of the polymerization of (L)- and (D)-2, or (L)- and (D)-5 with chiral oligomer complexes (L)-3(50) or (L)-6(100) suggests that the screw sense of the polymer backbone is not controlled kinetically, but rather that the thermodynamically stable screw sense is produced.