Distinct binding modes of a benzothiazole derivative confer structural bases for increasing ERK2 or p38α MAPK selectivity.

Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 2 (ERK2) and p38α MAP kinase (p38α MAPK), regulate various cellular responses. ERK2 is a drug target for treating many diseases, such as cancer, whereas p38α has attracted much attention as a promising drug target for treating inflammatory disorders. ERK2 is a critical off-target for p38α MAPK and vice versa. In this study, an allosteric ERK2 inhibitor with a benzothiazole moiety (compound 1) displayed comparable inhibitory activity against p38α MAPK. Crystal structures of these MAPKs showed that compound 1 bound to the allosteric site of ERK2 and p38α MAPK in distinct manners. Compound 1 formed a covalent bond with Cys162 of p38α MAPK, whereas this covalent bond was absent in the ERK2 complex even though the corresponding cysteine is conserved in ERK2. Structural dissection combined with computational simulations indicated that an amino acid difference in the allosteric site is responsible for the distinct binding modes of compound 1 with ERK2 and p38α MAPK. These structural insights underline the feasibility of developing highly selective and potent ERK2 and p38α MAPK inhibitors.

Long-term course of developmental dysplasia of the hip: follow-up of the non-operated hips of patients undergoing unilateral rotational acetabular osteotomy for twenty-four years.

PURPOSE: To follow-up the non-operated hips of patients who underwent unilateral rotational acetabular osteotomy (RAO) for bilateral developmental dysplasia of the hip (DDH) for a minimum of 20 years to clarify (1) the timing of onset of hip osteoarthritis (OA) in DDH, and (2) factors associated with the development of OA. METHODS: This study included 92 non-operated hips of patients who underwent unilateral RAO for bilateral DDH. We examined the timing of OA onset and total hip arthroplasty (THA) and the joint survival rate in the studied hips. Furthermore, the patients were divided into those with OA onset (progression group) and those without OA onset and compared in terms of lateral center-edge angle (LCEA), sharp angle, acetabular head index (AHI), acetabular roof obliquity (ARO), joint congruity, and the presence or absence of OA progression on the RAO side. RESULTS: The progression group experienced OA onset 12 years after RAO and underwent THA 6 years after OA onset. The 20-year joint survival rate was 73% with the endpoint of OA onset and 81% with the endpoint of THA. The progression group had significantly smaller LCEA and AHI and larger ARO. The risk of developing OA was 8.2 times greater in patients with LCEA ≤ 7° than in those with LCEA > 7°. CONCLUSION: The patients with OA progression group experienced OA onset at an average age of 55 years. A small LCEA (≤ 7°) was identified as a risk factor for the development of OA.

Chronological changes in the rate of surgical field contamination in the shoulder joint.

BACKGROUND: In shoulder surgery, low-virulence bacteria such as Cutibacterium acnes and coagulase-negative staphylococci can cause postoperative infection. However, the degree of sterility during surgery after disinfection is not known, and the efficacy of double skin preparation for such bacteria is unclear. This study aimed to evaluate chronological changes in the surgical field contamination rate in the shoulder joint and to compare single and double skin preparation. METHODS: In total, 126 shoulders in 121 patients undergoing shoulder surgery (64 men, 62 women; mean age 64 years) were enrolled. Patients were divided into two groups: single skin preparation, where the site was painted with 10% povidone iodine, and double skin preparation, where the site was treated with 1% chlorhexidine gluconate/83% isopropyl alcohol and painted 10% povidone iodine. Swab samples from the axillary and proximal areas in the surgical field were collected chronologically before starting surgery and at 30, 60, and 120 min after starting surgery (MAS). The contamination rate of each sample was compared and detected species were evaluated. RESULTS: The contamination rate for the axillary area was 48.4%, 85.9%, 95.3%, and 97.1% in the single-preparation group and 32.3%, 72.6%, 87.1%, and 91.2% in the double-preparation group before starting surgery and 30, 60, and 120 MAS, respectively, and that the proximal area was 12.5%, 26.6%, 29.7%, and 35.3% in the single-preparation group and 16.1%, 19.4%, 27.4%, and 38.2% in the double-preparation group, respectively. Significant differences were not seen between the groups by area or time point. Most detected species were Cutibacterium acnes and coagulase-negative staphylococci. CONCLUSIONS: The incidence of surgical field contamination in shoulder joint was high from immediately after starting surgery. In the axillary area, the contamination rates exceeded 70% from 30 MAS in both groups. Measures against infection should be instituted considering these findings when performing shoulder surgery.

Low entropic cost of binding confers high selectivity on an allosteric ERK2 inhibitor.

Extracellular signal-regulated kinase 2 (ERK2), a mitogen-activated protein kinase (MAPK), plays an essential role in physiological cellular processes and is a drug target for treating cancers and type 2 diabetes. A previous in silico screening study focusing on an allosteric site that plays a crucial role in substrate anchoring conferred an ERK2 inhibitor (compound 1). In this report, compound 1 was found to show high selectivity toward ERK2 compared with the nearest off-target p38α MAPK, and the crystal structure revealed that compound 1 binds to the allosteric site of ERK2. Fragment molecular orbital calculations based upon this crystal structure provided the structural basis to improve potency of compound 1 derivatives. Further computational studies uncovered that the low entropic cost of binding conferred the high selectivity of compound 1 toward ERK2 over p38α MAPK. These findings demonstrate the feasibility of developing potent and selective ERK2 inhibitors.

Identification of a novel target site for ATP-independent ERK2 inhibitors.

Extracellular signal-regulated kinase 2 (ERK2) controls vital physiological processes involving proliferation and differentiation and is a drug target molecule for many diseases such as cancers. In silico screening focusing on an allosteric site that plays a crucial role in substrate anchoring conferred an ERK2 inhibitor (compound 1). However, a competitive binding assay indicated that compound 1 did not bind to the allosteric site. Here, the crystal structure of ERK2 in complex with compound 1 revealed a novel binding site. This finding demonstrates the feasibility of developing new types of ERK2 inhibitors.

Arthroscopic Treatment of a Ganglion Cyst Originating from the Transverse Acetabular Ligament in the Hip Joint A Case Report.

Introduction: Intra-articular ganglion in the hip joint is rare. Here, we present a case of ganglion cyst originating from the transverse acetabular ligament (TAL) in the hip joint treated by arthroscopic surgery. Case Report: A 48-year-old man presented with the right groin pain after activity. A cystic lesion was found on magnetic resonance imaging. Under arthroscopic view, a cystic mass was identified between the TAL and ligamentum teres that discharged yellowish viscous liquid after puncture. The remaining lesion was resected in its entirety. A diagnosis of ganglion cyst was consistent with the histological findings. The patient has had no recurrence on magnetic resonance imaging as of 6 years postoperatively and had no complaints at the 6-year follow-up visit. Conclusion: Arthroscopic resection is useful for an intra-articular ganglion cyst in the hip joint.

What is the most cost-effective strategy for nasal screening and Staphylococcus aureus decolonization in patients undergoing total hip arthroplasty?

BACKGROUND: To reduce periprosthetic joint infection after total hip arthroplasty (THA), several nasal screening and decolonization strategies for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) have been performed. These include universal decolonization (UD; i.e., no screening and decolonization for all patients), universal screening and target decolonization (US; i.e., screening for all patients and decolonization for bacterial positive patients), and target screening and decolonization (TS; i.e., screening and decolonization for high-risk populations only). Although TS is the most cost-effective strategy, useful risk factors must be identified. The purpose of this study was to evaluate the presence of predictive factors that enable the TS strategy to be successfully implemented and to compare the costs of each strategy. METHODS: A total of 1654 patients scheduled for primary or revision THA (1464 female, 190 male; mean age 64 years) were screened prior to surgery for bacterial colonization of the nasal mucosa. Risk factors for positive MRSA and S. aureus (including both MRSA and MSSA) tests were analyzed according to the following parameters: sex, age ≥ 80 years, body mass index ≥ 30 kg/m2, antibiotic use within 3 years, corticosteroid use, serum albumin < 3.5 g/dL, glomerular filtration rate < 50 mL/min, presence of brain, thyroid, cardiac, or pulmonary disease, diabetes, asthma, smoking status, and whether revision surgery was performed. The average cost of each strategy was calculated. RESULTS: In total, 29 patients (1.8 %) tested positive for MRSA and 445 (26.9 %) tested positive for S. aureus. No parameters were identified as independent risk factors for MRSA and only female sex was identified as a risk factor for S. aureus (p = 0.003; odds ratio: 1.790; 95 % confidence interval: 1.210-2.640). The average cost of each strategy was 1928.3 yen for UD, 717.6 yen for US, and 717.6 yen for TS (for eradicating MRSA), and 1928.3 yen for UD, 1201.6 yen for US, and 1160.4 yen for TS (for eradicating S. aureus). CONCLUSIONS: No useful predictive parameters for implementing the TS strategy were identified. Based on cost implications, US is the most cost-effective strategy for THA patients.

Can sterility of stripped iodophor-impregnated plastic adhesive drape be maintained at the time of incision closure in total hip arthroplasty?

OBJECTIVE: The aim of this study was to analyze the contamination rates of the skin under the iodophor-impregnated plastic adhesive drape (IOD) at the time of incision closure in total hip arthroplasty (THA). METHODS: A total of 225 patients undergoing primary THA (28 men, 197 women; mean age=65 years; age range=30-85) were included in this study. After asepsis using a solution of 1% chlorhexidine with 83% alcohol by volume, the surgical site was painted with a 10% povidone-iodine solution, and IOD was attached tautly at the start of surgery. Swabs of the surgical site were collected as follows: swab A from the skin before IOD application, swab B from the surface of the IOD at the time of incision closure, and swab C from the skin after peeling back the IOD. The obtained samples were promptly sent for microbiological analysis. The contamination rate was determined for swabs A, B, and C, and the contamination rate of swab C was compared with that of swabs A and B, and the bacterial species were identified. RESULTS: Positive cultures were seen in 8 cases (3.6%) for swab A, 10 cases (4.4%) for swab B, and 22 cases (9.8%) for swab C. The contamination rate of swab C was significantly higher than that of swabs A (p=0.008) and B (p=0.028). Coagulase-negative Staphylococcus (n=10) and Cutibacterium acnes (n=7) were the most frequently cultured microorganisms from swab C. CONCLUSION: In THA, the contamination rate of the skin after peeling off the IOD before incision closure was higher than that of the skin immediately after sterilization with povidone-iodine and higher than that on the IOD at the time of incision closure. The detected bacterial species were considered clinically significant pathogens. Preventive measures against infection, such as minimizing stripping of the IOD or re-sterilizing bare skin after IOD stripping, should be instituted in consideration of these findings when performing THA using IOD.

Postoperative creatine kinase elevation following hip arthroscopy and associated risk factors.

OBJECTIVE: The aim of this study was to investigate postoperative CK and risk factors for CK elevation after hip arthroscopy. METHODS: This retrospective study reviewed 122 patients (50 males, 72 females; mean age, 44.1 years) who underwent hip arthroscopy from September 2012 to March 2018. For all patients, CK was investigated preoperatively, on postoperative days 1 and 3, and at postoperative weeks 1 and 2. Univariate and multivariate analysis was performed for parameters including sex, age, body mass index, preoperative glomerular filtration rate, diagnosis, duration of surgery, and duration of traction to determine the risk factors for CK > 10 upper limit of normal (CK > 10 ULN; 1900 IU/L for males and 1500 IU/L for females) after surgery. RESULTS: Mean CK was 104.7 ± 68.7 IU/L preoperatively and 839.2 ± 2214.0, 523.9 ± 1449.4, 186.0 ± 690.7, and 122.0 ± 307.1 IU/L on postoperative days 1 and 3 and at postoperative weeks 1 and 2, respectively. CK was significantly higher on postoperative days 1 and 3 than before surgery. In total, 11 patients (9.0%), including 8 males (16.0%) and 3 females (4.2%), had CK > 10 ULN. Younger age and longer duration of traction are independent risk factors for CK > 10 ULN. CONCLUSION: After hip arthroscopy, CK levels should be monitored, especially in young patients and cases of prolonged duration of traction during surgery. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Preoperative Pain Control in Arthroscopic Rotator Cuff Repair: Does It Matter?

BACKGROUND: The purpose of this study was to clarify the importance of preoperative pain control using corticosteroid injections in patients with persistent rest pain (RP) before arthroscopic rotator cuff repair (ARCR). METHODS: A total of 360 patients (374 shoulders) who underwent primary ARCR and were followed up for at least 2 years were enrolled. After one-to-one propensity score matching, 266 patients (145 men and 128 women, 273 shoulders) were included in the study. Their mean age was 65.2 ± 7.7 years (range, 42 to 88 years) at the time of surgery. The patients were divided into three groups: those who required several intra-articular or subacromial bursa corticosteroid injections preoperatively for refractory RP (group A+), those in whom RP was resolved preoperatively (group A-), and those who had no RP and did not require any injections (group B). The incidence of postoperative RP and preoperative and final follow-up American Shoulder and Elbow Surgeons (ASES) scores were compared among the three groups. RESULTS: The incidence of postoperative RP was significantly higher in group A+ (35/91 cases, 38.5%) than in group A- (10/91, 11.0%) and group B (7/91, 7.7%, p < 0.001 for both). The preoperative ASES score was significantly lower in group A+ (33.2 ± 14.2) than in group A- (53.9 ± 11.9) and group B (62.3 ± 11.2, p < 0.001 for both), and it was significantly lower in group A- than in group B (p = 0.000). The final follow-up ASES score was significantly lower in group A+ (92.1 ± 8.4) than in group A- (97.6 ± 5.4) and group B (99.0 ± 2.5, p < 0.001 for both). There was no significant difference in the final follow-up ASES score between group A- and group B (p = 0.242). CONCLUSIONS: Patients in whom preoperative RP could be resolved before surgery achieved postoperative outcomes comparable to those in patients who had no RP before surgery, whereas the outcomes in patients with refractory preoperative RP were inferior. The results suggest that preoperative pain control is important in patients undergoing ARCR.

Deletion of Eqtn in mice reduces male fertility and sperm-egg adhesion.

A number of sperm proteins are involved in the processes from gamete adhesion to fusion, but the underlying mechanism is still unclear. Here, we established a mouse mutant, the EQUATORIN-knockout (EQTN-KO, Eqtn - / - ) mouse model and found that the EQTN-KO males have reduced fertility and sperm-egg adhesion, while the EQTN-KO females are fertile. Eqtn - / - sperm were normal in morphology and motility. Eqtn - / - -Tg (Acr-Egfp) sperm, which were produced as the acrosome reporter by crossing Eqtn - / - with Eqtn +/+ -Tg(Acr-Egfp) mice, traveled to the oviduct ampulla and penetrated the egg zona pellucida of WT females. However, Eqtn - / - males mated with WT females showed significant reduction in both fertility and the number of sperm attached to the zona-free oocyte. Sperm IZUMO1 and egg CD9 behaved normally in Eqtn - / - sperm when they were fertilized with WT egg. Another acrosomal protein, SPESP1, behaved aberrantly in Eqtn - / - sperm during the acrosome reaction. The fertility impairment of EQTN/SPESP1-double KO males lacking Eqtn and Spesp1 (Eqtn/Spesp1 - / - ) was more severe compared with that of Eqtn - / - males. Eqtn - / - -Tg (Eqtn) males, which were generated to rescue Eqtn - / - males, restored the reduced fertility.

Target range of motion at 3 months after arthroscopic rotator cuff repair and its effect on the final outcome.

PURPOSE: The postoperative protocol after arthroscopic rotator cuff repair (ARCR) is still controversial. Some surgeons recommend slower rehabilitation in order to improve the integrity of the repair, while others prefer early range-of-motion (ROM) exercise to avoid postoperative stiffness. The purpose of this study was to determine target ROM (T-ROM) measurements at 3 months after ARCR that are predictive of eventual full recovery without structural failure. METHODS: The cases consisted of 374 shoulders in 360 patients who underwent primary ARCR and were followed up for at least 2 years. Forward flexion (FF) and side-lying external rotation (ER) were measured preoperatively at 3, 6, 9, 12, and 24 months after surgery, and the patients were divided into six subgroups according to the values for each type of ROM at 3 months (ROM-3M). In each subgroup, the final ROM at 24 months after surgery was compared to determine the T-ROM. The average ROMs with time and re-tear rate were then compared between the under-T-ROM and over-T-ROM groups. RESULTS: The only significant difference in FF was between the 120-129° and 110-119° ROM-3M groups. Therefore, the T-ROM for FF was determined to be 120°. Similarly, the T-ROM for ER was determined to be 20°. Each ROM in the over-T-ROM group was significantly better than that in the under-T-ROM group at all assessments. There was no significant difference in the re-tear rate between the groups. CONCLUSION: To acquire sufficient ROM in 2 years without high re-tear rate, a target FF of 120° and ER of 20° should be achieved within 3 months after surgery.

Human DP and EP2 prostanoid receptors take on distinct forms depending on the diverse binding of different ligands.

Human D-type prostanoid (DP) and E-type prostanoid 2 (EP2) receptors are G protein-coupled receptors and are regarded as the most closely related receptors among prostanoid receptors because they are generated by tandem duplication. The DP receptor-cognate ligand, prostaglandin D2 (PGD2 ) has the ability to activate not only DP receptors but also EP2 receptors. Likewise, the EP2 receptor-cognate ligand, prostaglandin E2 (PGE2 ) has the ability to activate DP receptors in addition to EP receptors in order to stimulate cAMP formation. However, since PGD2 and/or PGE2 activate DP and EP2 receptors to similar maximal levels, that is, their similar efficacies, differences between the ligands in each receptor have not yet been determined in detail except for their different affinities. Herein we demonstrated, using an in silico simulation to predict binding patterns among DP or EP2 receptors and PGD2 , PGE2 , or prostaglandin F2α as the reference prostanoid, that DP and EP2 receptors plausibly take on distinct forms depending on the diverse binding of different ligands. Since these ligands have the potential to make these receptors form distinct conformations with discrete signaling pathways, they are consequently regarded as endogenous biased ligands. Moreover, by using functional assays, the susceptibilities of the DP receptors to the noncognate ligands were approximately 10 times lower than those of EP2 receptors. Thus, EP2 receptors seem to be able to distinguish endogenous ligands better than DP receptors, thereby both receptors are plausibly gaining role-sharing functions with respect to one another as the copies of duplicated gene.

Identification of allosteric ERK2 inhibitors through in silico biased screening and competitive binding assay.

Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP competitive inhibitor binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50 <100 µM. Among them, two compounds revealed the concentration-dependent competition with PEP and could be lead compounds for antidiabetic medicine.

Arthroscopic reduction and internal fixation for fracture of the lateral process of the talus.

Fractures of the lateral process of the talus (LPT) are relatively rare. We describe arthroscopic reduction and internal fixation for a type I fracture of the LPT according to the Hawkins classification. Preoperative computed tomography is necessary to evaluate the type and displacement of the LPT fracture because this type of fracture is often overlooked on a plain radiograph. The ankle is approached through a standard medial portal as the working portal and an anterolateral portal as the viewing portal. A 2.7-mm-diameter 30° arthroscope is used. Hematoma and soft tissues around the talus are cleared with a motorized shaver, and the anterior and lateral aspects of the talar process are visualized. Fracture reduction is obtained by pushing the lateral fragment of the lateral process medially and is fixed temporally with a 1.1-mm guidewire from the medial portal under both arthroscopy and fluoroscopy. A headless compression screw is inserted through the guidewire. Arthroscopic reduction and internal fixation for a type I LPT fracture can be easily accomplished, and return to daily and sports activities can be achieved in a relatively short time.

Cementless Total Hip Arthroplasty in Hip Dysplasia with an Extensively Porous-Coated Cylindrical Stem Modified for Asians: A 12-Year Follow-Up Study.

Long-term outcomes of primary cementless total hip arthroplasty were examined for 198 hips of Asian patients with developmental dysplasia of the hip. AML stems were modified for patients' relatively small physique. Stable fixation was achieved despite various proximal femoral deformities. At follow up (mean 12.1 years), radiographs demonstrated fixation in all hips, with 100% stem survivorship. Radiographic changes revealed that the severity of stress-shielding was mild in 55% of hips, moderate in 26%, and severe in 19%. Longer follow up is needed to determine whether these changes will develop into clinical manifestations. A distal fixation stem can be a useful reconstruction option when application of a proximal fixation stem in primary total hip arthroplasty is difficult for various reasons.

Prediction of the interaction between spermidine and the G-G mismatch containing acceptor stem in tRNA(Ile): molecular modeling, density functional theory, and molecular dynamics study.

Polyamines, putrescine, spermidine (SPD), and spermine are closely linked to cell growth, and highly regulate the levels of transcription, translation and protein turnover. We propose that SPD stimulates the formation of Ile-tRNA(Ile) by inducing a selective structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Here, we provide insight into how SPD recognizes and stabilizes the G-G mismatch containing acceptor stem in tRNA(Ile) with molecular modeling (MM), density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The results of the MM and DFT calculations indicate that the negatively charged region of the G-G mismatch containing acceptor stem in tRNA(Ile) is preferentially recognized by positively charged SPD. In addition, MD simulations indicate that all of the positively charged amino groups of SPD under physiological conditions (N1(NH3(+)), N5(NH2(+)), and N10(NH3(+)) could form hydrogen bonds with tRNA(Ile) and trigger the SPD-induced stabilization and structural change of the G-G mismatch containing acceptor stem in tRNA(Ile). Thus, this approach should be useful for determining the preferential binding site and appropriate binding mode of polyamines on tRNA(Ile).

Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ): a patient-based evaluation tool for hip-joint disease. The Subcommittee on Hip Disease Evaluation of the Clinical Outcome Committee of the Japanese Orthopaedic Association.

BACKGROUND: The Japanese Orthopaedic Association Hip Score is widely used in Japan, but this tool is designed to reflect the viewpoint of health-care providers rather than that of patients. In gauging the effect of medical therapies in addition to clinical results, it is necessary to assess quality of life (QOL) from the viewpoint of patients. However, there is no tool evaluating QOL for Japanese patients with hip-joint disease. METHODS: With the aim of more accurately classifying QOL for Japanese patients with hip-joint disease, we prepared a questionnaire with 58 items for the survey derived from 464 opinions obtained from approximately 100 Japanese patients with hip-joint disease and previously devised evaluation criteria. In the survey, we collected information on 501 cases, and 402 were subjected to factor analysis. From this, we formulated three categories-movement, mental, and pain-each comprising 7 items, for a total of 21 items to be used as evaluation criteria for hip-joint function. RESULTS: The Cronbach's α coefficients for the three categories were 0.93, 0.93, and 0.95, respectively, indicating the high reliability of the evaluation criteria. The 21 items included some related to the Asian lifestyle, such as use of a Japanese-style toilet and rising from the floor, which are not included in other evaluation tools. CONCLUSIONS: This self-administered questionnaire may become a useful tool in the evaluation of not only Japanese patients, but also of members of other ethnic groups who engage in deep flexion of the hip joint during daily activities.

Knowledge-based identification of the ERK2/STAT3 signal pathway as a therapeutic target for type 2 diabetes and drug discovery.

Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which has an important role in the recognition of cognate kinases, phosphatases, scaffold proteins, and substrates. The peptide inhibitor was confirmed to exert effects in vitro and in vivo. The peptide inhibitor conferred a significant decrease in HOMA-IR levels on Day 28 compared with that in the vehicle group. Besides lowering the fasting blood glucose level, the peptide inhibitor also attenuated the blood glucose increment in the fed state, as compared with the vehicle group.

Osteoarthritis hip joints in Japan: involvement of acetabular dysplasia.

BACKGROUND: We conducted a nationwide epidemiologic study regarding hip osteoarthritis (OA) in Japan, and a previous report found these patients to be unique in comparison to Caucasians. This report focused on the data regarding each hip joint, and the involvement of acetabular dysplasia with hip OA was analyzed. METHODS: Seven hundred twenty OA hips were examined. Sixty-five joints with osteonecrosis of the femoral head and 215 non-OA contralateral joints of the unilateral patients were examined as controls. The revised system of stage classification for hip OA of the Japanese Orthopedic Association (JOA) was used according to the reproducibility in order to ensure reliable data from the multiple institutions. The acetabular dysplasia indexes were also chosen according to the reproducibility and measured in the radiograph of bilateral hip joints. The clinical score was assessed using the JOA scoring system. The relative risk of the grade of acetabular dysplasia indexes for hip OA was calculated as the odds ratio and the 95% confidence interval. RESULTS: The stage of the OA joints deteriorated with increasing age. The clinical scores also decreased. The grade of the acetabular dysplasia indexes of the OA joints was significantly higher than that of the control joints. Each index of acetabular dysplasia demonstrated significantly increased odds ratios for hip OA. Among the OA joints, the deterioration of the OA stage was found to be significantly associated with an increasing grade of acetabular dysplasia. The odds ratio for OA deterioration in the acetabular dysplasia index was also obtained. The joints of females tended to have a higher grade and prevalence of acetabular dysplasia than those of males. CONCLUSIONS: These findings confirmed a high prevalence of acetabular dysplasia in hip OA joints in Japan. Acetabular dysplasia was one of the most important factors associated with hip OA.