Panaxytriol Inhibits Lipopolysaccharide-Induced Microglia Activation in Brain Inflammation in Vivo.

Brain inflammation is a pathological characteristic of neurodegenerative diseases. In this condition, excessively activated microglia elevate proinflammatory mediator levels. We previously reported that panaxytriol inhibited lipopolysaccharide (LPS)-induced microglia activation in vitro. However, the effects of panaxytriol on microglia activation in vivo require confirmation. In the present study, we found that panaxytriol suppressed both microglia and astrocyte activation by injected LPS intracerebrally to mice with LPS-induced brain inflammation. Panaxytriol was more effective on microglia than astrocytes. Moreover, panaxytriol tended to reduce LPS-induced spontaneous motor activity dysfunction. These results suggested that panaxytriol could improve brain health by suppressing microglia activation in neurodegenerative diseases.

Inhibitory effect of panaxytriol on BV-2 microglial cell activation.

Activated microglia induce brain inflammation and neuronal death. Panaxytriol, ((3R,9R,10R)-Heptadec-1-en-4,6-diyne-3,9,10-triol), is a component of Panax ginseng C. A. Meyer extracts and activates the Nrf2-ARE signaling pathway. However, little is known about its effects on activated microglia in the brain. In this study, we investigated the effect of panaxytriol on lipopolysaccharide (LPS)-induced activated microglia in BV-2 cells. Panaxytriol suppressed LPS-induced NO production and inhibited the increase in iNOS protein expression in BV-2 cells. Besides, panaxytriol inhibited the mRNA expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6. The inhibitory effect of panaxytriol on microglia activation did not affect the Nrf2-ARE pathway and the MAPK pathway. However, panaxytriol suppressed LPS-induced NF-κB nuclear translocation. These results suggest that panaxytriol inhibits the LPS-induced activation of microglia via the inhibition of NF-κB signaling pathway.

[Clinical study to obtain true view of the glenohumeral joint on scapula-45].

Scapula-45 is an original roentogenographical technique to clarify objectively the function of the rotator cuff and scapulothoracic joint. This examination enables assessment of the function of the rotator cuff and scapulothoracic joint utilizing the radiographs of the glenohumeral joint. However, in the former technique, it was difficult for the technician to properly align the patient for the view of the true glenohumeral joint because of the individual postural difference of the patients, such as kyphosis. In the present study, we reported a new technique with the use of the acromion, coracoid process, and inferior angle of the scapula as a landmark to obtain the consistent radiographs of the glenohumeral joint.

Dietary whey hydrolysate with exercise alters the plasma protein profile: a comprehensive protein analysis.

OBJECTIVE: It has been shown that dietary whey protein accelerates glucose uptake by altering glycoregulatory enzyme activity in skeletal muscle. In the present study, we investigated the effect of dietary whey protein on endurance and glycogen resynthesis and attempted to identify plasma proteins that reflected the physical condition by a comprehensive proteomics approach. METHODS: Male c57BL/6 mice were divided into four groups: sedentary, sedentary with whey protein hydrolysate, exercise, and exercise with whey protein hydrolysate. The mice in the exercise groups performed treadmill running exercise five times per week for 4 wk. Protein profiling of plasma sample obtained from individuals was performed, as were measurements of endurance performance and the glycogen content of gastrocnemius muscle. RESULTS: After the training period, the endurance of mice fed the whey diet was improved compared with that of mice fed the control diet. Muscle glycogen content was significantly increased after 4 wk of exercise, and intake of whey protein led to a further increase in glycogen. Apolipoproteins A-II and C-I and ß(2)-glycoprotein-1 were found to be altered by training combined with the intake of whey protein, without significant changes induced by exercise or whey protein alone. CONCLUSION: Results of the present study suggest that these three proteins may be potential biomarkers of improved endurance and glycogen resynthesis and part of the mechanism that mediates the benefits of whey protein.

Surgical treatment for osteochondritis dissecans of the humeral capitellum.

BACKGROUND: Surgical treatments have been selected to treat advanced osteochondritis dissecans (OCD) of the humeral capitellum. PURPOSE: To evaluate the clinical results of surgical treatments for advanced capitellar OCD lesion and to clarify problems of poor clinical results. METHODS: Cases were reviewed for 27 patients with advanced OCD lesions treated operatively. All patients were male baseball players, with a mean of 13.3 years at the time of surgery. Drilling only was performed for 3 patients, fragment fixation for 13 patients, and removal of the detached fragment with drilling for four patients. Since 2004, reconstruction of the articular surface with use of osteochondral autograft from the rib has been performed for 7 patients with osteochondral defect. Mean follow-up was 37.4 months. Follow-up assessment included modified elbow rating system, evaluation of radiographs, and return to sports. RESULTS: Mean subjective score improved significantly from 70 to 96 postoperatively. Mean objective score improved significantly 71 to 81 postoperatively. A postoperative return to baseball was achieved by 25 patients. On the final radiographs, 4 patients showed flattening of >70% of the capitellum or degenerative changes, including insufficient remodeling of the lateral margin of the capitellum. Although patients could return to baseball, postoperative total arc of the elbow was decreased compared with the preoperative total arc. CONCLUSION: Surgical treatments were useful to restore advanced OCD lesions. Our results suggest that reconstruction of the lateral margin of the capitellum is important for achieving good clinical results. LEVEL OF EVIDENCE: Level 4.

Nonoperative treatment for osteochondritis dissecans of the capitellum.

BACKGROUND: Spontaneous healing potential and progression of osteochondritis dissecans of the capitellum have been unclear. HYPOTHESIS: Healing potential is high in the early stage of osteochondritis dissecans and low in the advanced stage. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This retrospective study examines 39 patients with osteochondritis dissecans of the capitellum who were treated conservatively. All patients were baseball players (mean age, 12.8 years). After initial examination, all patients were advised to stop heavy use of the elbow. Physical and radiographic examinations were regularly performed and assessed. Mean duration of follow-up was 14.4 months. RESULTS: Early-stage lesions were present in 30 patients, while 9 patients were diagnosed with advanced lesions. Open capitellar growth plates were observed in 17 patients, and closed capitellar growth plates were seen in 22 patients. On final radiography, 25 of 30 early-stage lesions were assessed as healed. However, only 1 of 9 advanced-stage lesions was assessed as healed. The remaining 8 advanced lesions were unimproved or progressed. Healing of lesions was seen in 16 of 17 patients with an open growth plate and in 11 of 22 patients with a closed growth plate, representing a significant difference between patients with open and closed growth plates (P < .05). CONCLUSION: Spontaneous healing potential of osteochondritis dissecans in early lesions, especially in patients with open capitellar growth plates, appears high, and nonoperative treatment is appropriate. Conversely, healing potential is extremely low in advanced osteochondritis dissecans lesions. Surgical intervention is recommended to achieve lesion healing in advanced cases.

New intramedullary nail for the surgical neck fracture of the proximal humerus in elderly patients.

BACKGROUND: Fractures of the proximal humerus are common and the repair of displaced fractures generally requires an operative approach. In elderly patients, osteoporosis makes internal fixation problematic and frequently contributes to failed fixation and poor clinical results. We have developed a new intramedullary nail (pin lock nail) for the repair of surgical neck fractures of the proximal humerus in patients with osteoporotic bones. A retrospective review is presented of the cases of 19 elderly patients with two-part or three-part fractures of the proximal humerus treated using the pin lock nail. METHODS: We treated 19 elderly patients with a mean age of 70.5 years. There were 13 two-part surgical neck fractures, 3 two-part surgical neck fractures with non-displaced greater tuberosity fracture, and 3 three-part surgical neck fractures with greater tuberosity fracture. All fractures were treated using the pin lock nail. Clinical results were evaluated using the Japanese Orthopaedic Association score at the last follow-up examination. On radiographic evaluation, duration to bone union of the fracture, backing out of the pin and screw, penetration of the proximal pin, and varus angulations of the humeral neck were examined. RESULTS: Mean duration of follow-up was 14 months (range 6-54 months). All fractures had united at an average of 3.3 months after surgery. No backing out of the pin and screw or penetration of the proximal locking pin was seen at the time of last follow-up. Thirteen of the 16 patients had no or minimal varus angulations of the humeral neck (< or =10 degrees). The mean overall JOA score was 84.3 points (range 65.5-100). CONCLUSIONS: Our data show that using the pin lock nail for the treatment of two-part and three-part humeral fractures is a reliable procedure, providing good results with careful postoperative management.

Determination of in vivo glenohumeral translation using fluoroscopy and shape-matching techniques.

The purpose of this study was to investigate glenohumeral translation in-vivo during active shoulder abduction in the scapular plane. Three-dimensional (3D) models of 9 shoulders were created from CT scans. Fluoroscopic views aligned to the plane of the scapula were recorded during active arm abduction with neutral rotation. 3D motions were determined using model-based 3D-to-two-dimensional (2D) registration. Humeral translation was referenced to the glenoid center in the superior/inferior direction. The humerus moved an average of 1.7 mm superior with arm abduction, from an inferior location to the glenoid center. The humeral head was centered within 1 mm from the glenoid center above 80 degrees abduction. Variability in glenohumeral translation between shoulders decreased significantly from initial to final arm abduction. Our findings agree with some authors' observations of inferior-to-central translation of the humerus and behavior as a congruent ball and socket. We believe this information will help improve the understanding of shoulder function.

Role of C-terminal region of Staphylococcal nuclease for foldability, stability, and activity.

The role of the C-terminal region of Staphylococcal nuclease (SNase) was examined by deletion mutation. Deletions up to eight residues do not affect the structure and function. The structure and enzymatic activity were partially lost by deleting Ser141-Asn149 (Delta141-149), and deletion of Trp140-Asn149 (Delta140-149) resulted in further loss of structure and activity. A 13-residue deletion showed the same effect as the 10-residue deletion. Both Ser141Gln and Ser141Ala mutations for an eight-residue deletion mutant did not alter properties as well as Ser141A1a for full-length SNase. In contrast, Trp140Ala mutation for Delta141-149 shows the same effect as the deletion of Trp140. Trp140Ala mutation for full-length SNase causes the loss of native structure. These observations indicate the significance of the 140th and the 141st residues. The side-chain of the 140th residue is required to be tryptophan; however, the backbone of the 141st residue is solely critical for foldability, but the side-chain information is not crucial. All of the mutants that take a non-native conformation show enzymatic activity and inhibitor-induced folding, suggesting that foldability is required for the activity.

Structural change of site-directed mutants of PYP: new dynamics during pR state.

The energetics, protein dynamics, and diffusion coefficients of three mutants of photoactive yellow protein, R52Q, P68A, and W119G, were studied by the transient grating and pulsed laser-induced photoacoustic method. We observed a new dynamics with a lifetime of approximately 1 micro s in the transient grating signal, which is silent by the light absorption technique. This fact indicates that, after the structure change around the chromophore is completed (pR(1)), the protein part located far from the chromophore is still moving to finally create another pR (pR(2)) species, which can transform to the next intermediate, pB. Although the kinetics of pR(2)-->pB-->pG are very different depending on the mutants, the enthalpies of the first long-lived (in micro seconds, 100-micro s range) intermediate species (pR(2)) are similar and very high for all mutants. The diffusion coefficients of the parent (pG) and pB species of the mutants are also similar to that of the wild-type photoactive yellow protein. From the temperature dependence of the volume change, the difference in the thermal expansion coefficients taken as indicator of the flexibility of the structure between pG and pR(2) is measured. They are also similar to that of the wild-type photoactive yellow protein. These results suggest that the protein structures of pR(2) and pB in these mutants are globally different from that of pG, and this structural change is not altered so much by the single amino acid residue mutation. This is consistent with the partially unfolded nature of these intermediate species. On the other hand, the volume changes during pR(1)-->pR(2) are sensitive to the mutations, which may suggest that the volume change reflects a rather local character of the structure, such as the chromophore-protein interaction.

Effect of organic anions on the photoreaction of photoactive yellow protein.

In order to clarify changes in the structure and surface properties of photoactive yellow protein (PYP) upon light absorption, the spectroscopic properties and solution structure of its photo-intermediate (PYP(M)) were examined in the presence of various anions. At identical ionic strengths, citrate slowed the decay rate of PYP(M) more than acetate. Although the absorption spectrum in the dark was not affected by organic anions, citrate induced a 5-nm blue shift of the absorption maximum for PYP(M). Solution X-ray scattering experiments indicated that the radius of gyration (Rg) and apparent molecular weight in the dark were constant in all buffer systems. However, the Rg of PYP(M) in citrate buffer at high concentration was 16.2 (+/-0.2) A, while the Rg of PYP(M) in acetate buffer was 15.6 (+/-0.2) A. The apparent molecular weight increased 7% upon PYP(M) formation in citrate buffer at high concentration compared to other conditions. These results suggest that citrate molecules specifically bind to PYP(M). A cluster of basic amino acid residues with a hydrogen bond donor would be exposed upon PYP(M) formation and responsible for the specific binding of citrate.

MR arthrography of shoulders after suture-anchor Bankart repair.

PURPOSE: To determine the ability of magnetic resonance (MR) arthrography to depict the anatomic reestablishment of the capsulolabral complex after suture-anchor Bankart repair. MATERIALS AND METHODS: Thirty patients (25 men, five women; mean age, 28 years) who had undergone suture-anchor Bankart repair of one shoulder underwent MR arthrography before second-look arthroscopy. Ninety-eight anchors were used for the sutures. MR arthrographic diagnosis of anatomic reestablishment of the capsulolabral complex was correlated with arthroscopic findings. Contingency table analysis was performed to determine the relationship between MR arthrographic findings and arthroscopic findings. RESULTS: MR findings of reattachment of the capsulolabral complex were in agreement with arthroscopic findings in 93 anchor points (accuracy, 93 of 98 anchor points; 95%). In 28 shoulders, oblique transverse images obtained with the shoulder in the abduction and external rotation position showed that the anterior band of the inferior glenohumeral ligament (AIGHL) abutted the humeral head and that reattachment of the AIGHL to the glenoid rim was seamless. Arthroscopy revealed satisfactory reestablishment of the capsulolabral complex in these shoulders. In the remaining two shoulders, a pool of contrast material was seen between the AIGHL and humeral head and a "divot" was detected at the point of reattachment of the AIGHL to the glenoid rim. Arthroscopy revealed unsatisfactory reestablishment of the capsulolabral complex. MR arthrographic findings of reattachment of the AIGHL were significantly associated with arthroscopic findings of reestablishment of the capsulolabral complex (P <.01). CONCLUSION: MR arthrography can be reliably used for the postoperative assessment of suture-anchor Bankart repair.