This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint ...capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.
Multiple cytokines play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The appropriate intracellular signalling pathways must be activated via cytokine receptors on the cell ...surface, and the tyrosine kinases transduce the first 'outside to in' signals to be phosphorylated after receptor binding to its ligand. Among them, members of the Janus kinase (JAK) family are essential for the signalling pathways of various cytokines and are implicated in the pathogenesis of RA. The in vitro, ex vivo and in vivo effects of a JAK inhibitor CP-690,550 (tofacitinib) for the treatment of RA are reported. In vitro experiments indicated that the effects of tofacitinib were mediated through suppression of interleukin 17 (IL-17) and interferon γ production and proliferation of CD4 T cells, presumably Th1 and Th17. A treatment study was conducted in the severe combined immunodeficiency (SCID)-HuRAg mice, an RA animal model using SCID mice implanted with synovium and cartilage from patients. Tofacitinib reduced serum levels of human IL-6 and IL-8 in the mice and also reduced synovial inflammation and invasion into the implanted cartilage. A phase 2 double-blind study using tofacitinib was carried out in Japanese patients with active RA and inadequate response to methotrexate (MTX). A total of 140 patients were randomised to tofacitinib 1, 3, 5, 10 mg or placebo twice daily and the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12, a primary end point, was significant for all tofacitinib treatment groups. Thus, an orally available tofacitinib in combination with MTX was efficacious and had a manageable safety profile. Tofacitinib at 5 and 10 mg twice a day appears suitable for further evaluation to optimise the treatment of RA.
After anterior cruciate ligament (ACL) injury, a decrease in muscle strength associated with muscle atrophy is frequently observed. The temporal and spatial effects of reconstructive surgery on ...muscle atrophy have not been examined in detail. This study aimed to 1) reveal the short and mid-term effects of reconstructive surgery on muscle atrophy, and 2) investigate the differences in the degree of atrophy after ACL reconstruction in the hindlimb muscles. ACL transection with or without reconstructive surgery was performed unilaterally on the knees of rats. Untreated rats were used as controls. At one or four weeks post-surgery, the relative muscle wet weights (wet weight/body weight) of the hindlimb muscles were calculated to assess atrophy. At one week post-surgery, muscle atrophy was induced by ACL transection and further aggravated by reconstructive surgery. Reconstructive surgery facilitated recovery from muscle atrophy in some muscles compared with those without reconstructive surgery (ACL transection alone) at four weeks post-surgery. Muscle atrophy after ACL reconstruction was greater in the rectus femoris and plantar flexors than in the semitendinosus and plantar extensors at one week post-surgery. These results indicate that reconstructive surgery exacerbates muscle atrophy in the first week post-surgery, while facilitating recovery between the first and fourth week post-surgery. After reconstructive surgery, muscle atrophy was observed not only in the quadriceps and hamstrings, but also in the lower leg muscles, suggesting the need for muscle strengthening interventions for the lower leg muscles as well as the quadriceps and hamstrings.
Redox-sensitive metallic elements, Mn and Fe, are oxidized in deep sea waters and form abundant ferromanganese crusts and nodules on the world's ocean floors at ultraslow rates of growth. This ...process of oxidation and the mechanism of precipitation are yet unknown. In this paper, the results of the first successful, long-term, on-site experiment of mineral precipitation that ascertains modern, ongoing hydrogenetic deposition of oxide materials from normal seawaters at water depths of 900-4500 m of geologically active and inactive environments are presented. We succeeded in the in-situ precipitation experiment on the sea floor and characterized the precipitates using high-resolution and submicron-scale chemical, mineralogical, and structural analyses. The installed artificial plates of glass, ceramics, and plastic yielded spread-out particles of sizes varying from one to a few micrometers in diameter, of coccoid-like irregular shapes, with a maximum of 1,000-10,000 individual particles/mm
/year after 12-15 years of exposure. The results indicated a continuous substantial growth of the hydrogenetic minerals if both Mn and Fe are supplied to the bottom waters. The mineralogical, chemical, and structural properties of the precipitates are similar to those of the natural precipitates on the seabed that are made up of hydrogenetic ferromanganese crusts and nodules, together with settling sediments, suspended hydrothermal particles, or microbial precipitates from cultivated Mn-oxidizing bacteria. Our work presents new realistic insight into proposed genetic models of marine hydrogenetic ferromanganese deposits in modern diverse ocean environments.
ABSTRACT We present simultaneous Nuclear Spectroscopic Telescope Array (NuSTAR ) and Suzaku observations of the X-ray binary Cygnus X-1 in the hard state. This is the first time this state has been ...observed in Cyg X-1 with NuSTAR, which enables us to study the reflection and broadband spectra in unprecedented detail. We confirm that the iron line cannot be fit with a combination of narrow lines and absorption features, instead requiring a relativistically blurred profile in combination with a narrow line and absorption from the companion wind. We use the reflection models of García et al. to simultaneously measure the black hole spin, disk inner radius, and coronal height in a self-consistent manner. Detailed fits to the iron line profile indicate a high level of relativistic blurring, indicative of reflection from the inner accretion disk. We find a high spin, a small inner disk radius, and a low source height and rule out truncation to greater than three gravitational radii at the 3 confidence level. In addition, we find that the line profile has not changed greatly in the switch from soft to hard states, and that the differences are consistent with changes in the underlying reflection spectrum rather than the relativistic blurring. We find that the blurring parameters are consistent when fitting either just the iron line or the entire broadband spectrum, which is well modeled with a Comptonized continuum plus reflection model.
Therapeutic approaches to treat joint contracture after anterior cruciate ligament (ACL) reconstruction have not been established. Arthrofibrosis accompanied by joint inflammation following ACL ...reconstruction is a major cause of arthrogenic contracture. In this study, we examined whether anti-inflammatory treatment using low-level laser therapy (LLLT) can prevent ACL reconstruction-induced arthrogenic contracture. Rats underwent ACL transection and reconstruction surgery in their right knees. Unoperated left knees were used as controls. After surgery, rats were reared with or without daily LLLT (wavelength: 830 nm; power output: 150 mW; power density: 5 W/cm2; for 120 s/day). We assessed the passive extension range of motion (ROM) after myotomy at one and two weeks post-surgery; the reduction in ROM represents the severity of arthrogenic contracture. ROM was markedly decreased by ACL reconstruction at both time points; however, LLLT partially attenuated the decrease in ROM. One week after ACL reconstruction, the gene expression of the proinflammatory cytokine interleukin-1β in the joint capsule was significantly upregulated, and this upregulation was significantly attenuated by LLLT. Fibrotic changes in the joint capsule, including upregulation of collagen type I and III genes, shortening of the synovium, and thickening were caused by ACL reconstruction and seen at both time points. LLLT attenuated these fibrotic changes as well. Our results indicate that LLLT after ACL reconstruction could attenuate the formation of arthrogenic contracture through inhibition of inflammation and fibrosis in the joint capsule. Thus, LLLT may become a novel therapeutic approach for ACL reconstruction-induced joint contracture.
Purpose
Cultural differences are hypothesized to influence patients’ Quality of Life (QoL) reports. However, there is a lack of empirical cross-cultural studies comparing QoL of patients with cancer. ...This study aims to compare QoL of women with breast cancer in the Netherlands and Japan, and to investigate the association of QoL with sociodemographic, clinical, and psychological variables (illness perceptions).
Methods
Dutch (
n
= 116) and Japanese (
n
= 148) women with early breast cancer undergoing chemotherapy completed the EORTC QLQ-C30 and Brief Illness Perception Questionnaire immediately before their second cycle of chemotherapy.
Results
Dutch women reported poorer Physical, Role, Emotional, and Cognitive functioning than Japanese women. Additionally, illness perceptions were significantly different in Japan and the Netherlands, but these did not vary across treatment type. In Japan, QoL of women receiving AC-chemotherapy was better than that of women receiving FEC-chemotherapy, whereas in the Netherlands, QoL did not vary as a function of chemotherapy. Illness perceptions about symptom severity, adverse consequences, and emotional representations were negatively related to most domains of patients’ QoL in both countries. Adding illness perceptions as covariates to the ANOVA analyses rendered the effects of country and treatment type on QoL non-significant.
Conclusions
Comparing Dutch and Japanese women with early breast cancer revealed important differences in treatment modalities and illness perceptions which both appear to influence QoL. Perceptions about cancer have been found to vary across cultures, and our study suggests that these perceptions should be considered when performing cross-cultural studies focusing on patient-reported outcomes.
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