Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

OBJECTIVE: To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. DESIGN: Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. RESULTS: Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). CONCLUSION: T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.

Hidden osteophyte formation on plain X-ray is the predictive factor for development of knee osteoarthritis after 48 months--data from the Osteoarthritis Initiative.

OBJECTIVE: To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS: Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS: Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION: Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model.

OBJECTIVE: Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. DESIGN: OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. RESULTS: Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. CONCLUSION: IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model.

OBJECTIVE: To investigate the longitudinal angiogenic activity of subchondral bone and cartilage during the progression of osteoarthritis (OA) using a rabbit model of OA. MATERIALS AND METHODS: OA was surgically induced by anterior cruciate ligament transaction (ACLT) in left knee of 12 months old female New Zealand white rabbits (n = 33). Histological examination, immunohistochemistry, and angiogenic activity assay was done at 0, 2, 4, 6, 8, 12 weeks after ACLT. Histologic evaluation was performed with haematoxylin and eosin, safranin-O staining to assess the OA change of medial femoral condyle (MFC) and lateral femoral condyle (LFC). CD31 immunohistochemistry was performed to confirm the vascular invasion at osteochondral junction. A co-cultured tubule formation assay was conducted to evaluate angiogenic activity of the subchondral bone and cartilage of MFC and LFC as well as synovium. Association between histological changes, angiogenic activity, and vascular invasion were evaluated. RESULTS: OA changes increased in a time-dependent manner both in MFC and LFC. Angiogenic activity of subchondral bone showed a monomodal change during the OA progression, achieved a peak in the early to progressive stage and decreased to normal level in the late stage of OA. Surge of vascular invasion was observed following the increase of angiogenic activity in the progressive stage of OA. Angiogenic activity of cartilage did not change during the course of OA progression. CONCLUSION: Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.

Endoscopic mucosal resection of superficially spreading colonic neoplasms larger than 5 cm in the right colon after injection of dilute sodium hyaluronate: report of two cases.

Submucosal injection is the most important procedure for the safe performance of endoscopic mucosal resection in the large intestine while avoiding the risk of perforation. We used dilute sodium hyaluronate containing Bosmin and achieved safe piecemeal resection of large superficial tumors in the right colon in two patients. Piecemeal snare resection is considered to be acceptable if all the tissue pieces can be collected for histopathological diagnosis.

[Optimal lymph node dissection for colorectal cancer].

Previous studies on the distribution of positive lymph nodes have revealed that the colon should be resected 10 cm from the tumor on both sides and that the intermediate nodes along the main vessel should be dissected in patients with colon cancer. In rectal cancer, superior lymphatic spread along the inferior mesenteric artery (IMA) is the main metastatic route. The IMA should be dissected immediately after the bifurcation of the left colic artery, and the intermediate lymph nodes should be removed. The positive rate of the lateral lymph nodes is about 10%. The rate of local failure is high and the prognosis is poor in patients with positive lateral lymph nodes, even if the lateral lymph nodes have been dissected. However, it has been reported that lateral lymph node dissection combined with excision of the internal iliac vessels results in good disease-free survival in patients with positive lateral nodes. Therefore the indications for lateral node dissection remain controversial. Lymphatic spread into the mesorectum on the anal side has been shown to be an important factor in local failure. The mesorectum should be resected for up to 4 or 5 cm from the inferior tumor margin in middle rectal cancer, and the entire mesorectum should be removed in lower rectal cancer. Nerve tissue preserved in pelvic autonomic nerve-preserving surgery contains a small amount of lymphoid tissue and lymph nodes. Therefore the extent of lymph node dissection and the area of autonomic nerves to be preserved based on tumor site or tumor penetration remain controversial.

Chemo-enzymatic D-enantiomerization of DL-lactate.

We investigated the total conversion of racemic lactate, L-lactate, and pyruvate into D-lactate, which is very useful as a starting material for the synthesis of chiral compounds and much more valuable than the L-enantiomer by means of coupling of L-specific oxidation of the racemate with L-lactate oxidase and non-enantiospecific reduction of pyruvate to DL-lactate with sodium borohydride. In this one-pot system, L-lactate was enantiospecifically oxidized to an achiral product, pyruvate, which was chemically reduced to DL-lactate leading to a turnover. Consequently, either DL-lactate, L-lactate, or pyruvate was fully converted to the D-enantiomer. We optimized the reaction conditions: DL-lactate was converted to D-lactate in 99% of the theoretical yield and with more than 99% enantiomeric excess. DL-alpha-Hydroxybutyrate and alpha-ketobutyrate were converted also to D-alpha-hydroxybutyrate in the same way, though slowly.