The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin‐1β in human chondrocytes

In this study, we examined the effects of overexpression of SIRT1 on IL‐1β‐induced gene expression changes in human chondrocytes to explore a protective role of SIRT1 in human chondrocytes. SIRT1 was overexpressed in human chondrocytes by expression plasmid under stimulation with IL‐1β. SIRT1 was also inhibited by siRNA under stimulation with IL‐1β. Gene expression changes were examined by real‐time PCR. The interaction of SIRT1 and p65 (NF‐κB) were examined by Western blotting. SIRT1, MMP‐13, and ADAMTS‐5 expressions in human cartilage were examined by immunohistochemistry. IL‐1β stimulation significantly up‐regulated MMP‐1, 2, 9, and 13 and ADAMTS‐5. Overexpression of SIRT1 significantly inhibited the up‐regulation of those genes caused by IL‐1β while the inhibition of SIRT1 further increased them. In addition, the overexpression of SIRT1 markedly reduced the IL‐1β‐induced acetylation of p65. SIRT1 expression was clearly detected in the non‐OA cartilage while MMP‐13 and ADAMTS‐5 were undetectable. In contrast, in the OA cartilage, SIRT1 expression was decreased while MMP‐13 and ADAMTS‐5 were increased. Our observations suggested that SIRT1 can play a protective role by suppressing IL‐1β‐induced expressions of cartilage‐degrading enzymes partially through the modulation of the NF‐κB pathway. SIRT1 overexpression might be a new therapeutic approach for OA. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 531–537, 2013     

Ca2+ sensitization in contraction of human bladder smooth muscle

PURPOSE: The role of Ca2+ sensitization in the contraction of human bladder urinary smooth muscle (UBSM) was investigated. MATERIALS AND METHODS: Simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension in fura-2 loaded intact strips and receptor coupled strips permeabilized with alpha-toxin were applied. Protein expressions was confirmed by Western blot analysis. RESULTS: In intact fura-2 loaded strips 1 microM carbachol (CCh) induced a greater contraction and a lower [Ca2+]i elevation than that induced by 60 mM K depolarization. In alpha-toxin permeabilized strips 1 microM CCh induced contraction at constant [Ca2+]i and produced a leftward shift in the [Ca2+]i-tension relationship. RhoA, Rho-associated kinase (ROCK) I, ROCK II and CPI-17 proteins were expressed in human UBSM. In intact fura-2 loaded strips the application of 3 microM Y-27632, a ROCK inhibitor, or 3 microM bisindolylmaleimide I (GF109203X), a protein kinase C inhibitor, during the sustained phase of contraction induced by 1 microM CCh induced relaxation without changing [Ca2+]i. In alpha-toxin permeabilized strips the application of 3 microM Y-27632 or 3 microM GF109203X during the sustained contraction induced by 0.3 microM Ca plus 10 microM guanosine triphosphate and 1 microM CCh induced relaxation at constant [Ca2+]i. CONCLUSIONS: These results indicate that in human UBSM CCh induces contraction, not only by increasing [Ca2+]i, but also by increasing the Ca2+ sensitivity of the contractile apparatus in a ROCK and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways may represent an alternative target in the treatment of overactive bladder.     

Prosthetic alignment and sizing in computer-assisted total knee arthroplasty

We implanted 60 posterior stabilized total knee prostheses (P.F.C. Sigma, DePuy, Warsaw, USA). In 30 cases, we used a CT-free navigation system (Vector Vision, Brain LAB, Heimstetten, Germany), and in 30 matched-paired controls, we used a conventional manual implantation. We compared postoperative long-leg radiographs in the two groups. The results revealed a significant difference in favor of navigation. In addition, we compared the preoperative anteroposterior dimension of the femoral condyle with the postoperative value. While there were no significant differences in the preoperative anteroposterior dimension of the femoral condyle between the two groups, the postoperative value in the navigation group was significantly larger than that of the preoperative value. Therefore, surgeons using navigation systems should guard against the possibility of oversizing when determining the size of the femoral component.

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Résumé Nous avons implanté 60 prothèses totales postéro-stabilisées du genou (P.F.C. Sigma, DePuy). Dans 30 cas nous avons utilisé un système de navigation sans scanner (Vector vision R, Laboratoire du Cerveau, Heimstetten, Allemagne) et dans 30 contrôles appairés nous avons utilisé une implantation manuelle habituelle. Nous avons comparé les grandes radiographies postopératoires des membres inférieurs dans les deux groupes. Les résultats ont révélé une différence notable en faveur de la navigation. De plus nous avons comparé la dimension antéro-postérieure du condyle fémoral avant lintervention avec la valeur postopératoire. Tandis quil ny avait pas de différence notable dans la dimension antéro-postérieure préopératoire du condyle fémoral entre les deux groupes, la valeur postopératoire dans le groupe de la navigation était nettement plus grande que la valeur préopératoire. Par conséquent les chirurgiens qui utilisent des systèmes de navigation doivent prendre garde à ne pas implanter un composant fémoral sur-dimensionné.

     

Differences in spatial and temporal frequency interactions between central and peripheral parts of the feline area 18

The visual system demonstrates significant differences in information processing abilities between the central and peripheral parts of the visual field. Optical imaging based on intrinsic signals was used to investigate the difference in stimulus spatial and temporal frequency interactions related to receptive field eccentricity in the cat area 18. Changing either the spatial or the temporal frequency of grating stimuli had a significant impact on responses in the cortical areas corresponding to the centre of the visual field and more peripheral parts at 10 degrees eccentricity. The cortical region corresponding to the centre of the gaze was tuned to 0.4 cycles per degree (c/deg) for spatial frequency and 2 Hz for temporal frequency. In contrast, the cortical region corresponding to the periphery of the visual field was tuned to a lower spatial frequency of 0.15 c/deg and a higher temporal frequency of 4 Hz. Interestingly, when we simultaneously changed both the spatial frequency and the temporal frequency of the grating stimuli, the responses were significantly different from those estimated with an assumption of independence between the spatial and temporal frequency in the cortical region corresponding to the periphery of the visual field. However, in the cortical area corresponding to the centre of the gaze, spatial frequency showed significant independence from temporal frequency. These properties support the notion of relative specialization of visual information processing for peripheral representations in cortical areas.     

Subarachnoid hemorrhage in a case of segmental arterial mediolysis with coexisting intracranial and intraabdominal aneurysms

The authors report the rare case of a 58-year-old man with segmental arterial mediolysis (SAM) with associated intracranial and intraabdominal aneurysms, who suffered subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm. This disease primarily involves the intraabdominal arterial system, resulting in intraabdominal and retroperitoneal hemorrhage in most cases. The patient presented with severe headache and vomiting. The CT scans of the head revealed SAH. Cerebral angiography revealed 3 aneurysms: 1 in the right distal anterior cerebral artery (ACA), 1 in the distal portion of the A(1) segment of the right ACA, and 1 in the left vertebral artery. The patient had a history of multiple intraabdominal aneurysms involving the splenic, gastroepiploic, gastroduodenal, and bilateral renal arteries. He underwent a right frontotemporal craniotomy and fibrin coating of the dissecting aneurysm in the distal portion of the A(1) segment of the right ACA, which was the cause of the hemorrhage. Follow-up revealed no significant changes in the residual intracranial and intraabdominal aneurysms. An SAH due to SAM with associated multiple intraabdominal aneurysms is extremely rare. The authors describe their particular case and review the literature pertaining to SAM with associated intracranial and intraabdominal aneurysms.     

A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209)

OBJECTIVE: We performed a prospective randomized trial in patients with potentially resectable stage IIIA N2 non-small cell lung cancer to confirm the efficacy of induction chemotherapy before surgical resection. METHODS: Patients with stage IIIA N2 non-small cell lung cancer, all with histologically or cytologically confirmed metastases to the ipsilateral mediastinal lymph nodes, were randomly assigned to receive either three cycles of induction chemotherapy (cisplatin at 80 mg/m(2) on 1 day and vindesine at 3 mg/m(2) on 2 days) followed by surgery or surgery alone. RESULTS: This trial was prematurely terminated because the accrual rate was too slow, which lowered the study's statistical power considerably. From June 1993 through April 1998, a total of 62 patients were enrolled, and 31 patients were assigned to each treatment group. The objective clinical response rate of induction chemotherapy was 28%. Complete resection was achieved in 20 patients in the induction chemotherapy group (65%) and 24 in the surgery alone group (77%). Median follow-up was 6.2 years. Median overall survivals were 17 months for the induction group and 16 months for the surgery alone group. The estimated 1-, 3-, and 5-year survivals, respectively, were 68% (95% confidence interval 51%-85%), 23% (95% confidence interval 8%-38%), and 10% (95% confidence interval 0%-20%) for the induction chemotherapy group and 65% (95% confidence interval 48%-82%), 26% (95% confidence interval 11%-41%), and 22% (95% confidence interval 7%-37%) for the surgery alone group. There was no statistically significant difference in survival between the groups (P =.5274). Treatment-related death was not observed in either group. CONCLUSION: This randomized trial to compare induction chemotherapy (cisplatin and vindesine) followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer did not demonstrate a survival difference between the groups, although this may have been because the statistical power was limited.     

Hepatocyte growth factor and transforming growth factor β1 contribute to regeneration of small-for-size liver graft immediately after transplantation

Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor- (TGF-) and transforming growth factor-1 (TGF-1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217±12% and 178±10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF- levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.     

Pre-anesthetic evaluation can play a crucial role in the determination of airway management in a child with oropharyngeal tumor

We experienced a case of a huge hemangioma occupying the oropharyngeal space in an 11-year-old child. Although urgent surgical tracheostomy under local anesthesia was suggested initially, medical interview and findings of computerized tomography and fiberoptic laryngoscopy revealed that the airway of the patient was relatively stable when she was in the semi-left decubitus position. General anesthetic induction would have had potential risks of airway obstruction. Thus, after placing the patient in the semi-left decubutus position, we chose semi-awake induction to secure the airway. With a small dose of fentanyl, we accomplished orotracheal intubation. In this report, we discuss the importance of referring to an airway management algorithm when encountering a difficult airway.     

Cyclin‐Dependent Kinase Inhibitor‐1‐Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation

Osteoarthritis (OA) is a multifactorial disease, and recent data suggested that cell cycle–related proteins play a role in OA pathology. Cyclin‐dependent kinase (CDK) inhibitor 1 (p21) regulates activation of other CDKs, and recently, we reported that p21 deficiency induced susceptibility to OA induced by destabilization of the medial meniscus (DMM) surgery through STAT3‐signaling activation. However, the mechanisms associated with why p21 deficiency led to susceptibility to OA by the STAT3 pathway remain unknown. Therefore, we focused on joint inflammation to determine the mechanisms associated with p21 function during in vitro and in vivo OA progression. p21‐knockout (p21^?/?) mice were used to develop an in vivo OA model, and C57BL/6 (p21^+/+) mice with the same background as the p21^?/? mice were used as controls. Morphogenic changes were measured using micro‐CT, IL‐1β serum levels were detected by ELISA, and histological or immunohistological analyses were performed. Our results indicated that p21‐deficient DMM‐model mice exhibited significant subchondral bone destruction and cartilage degradation compared with wild‐type mice. Immunohistochemistry results revealed p21^?/? mice susceptibility to OA changes accompanied by macrophage infiltration and enhanced MMP‐3 and MMP‐13 expression through IL‐1β‐induced NF‐κB signaling. p21^?/? mice also showed subchondral bone destruction according to micro‐CT analysis, and cathepsin K staining revealed increased numbers of osteoclasts. Furthermore, p21^?/? mice displayed increased serum IL‐1β levels, and isolated chondrocytes from p21^?/? mice indicated elevated MMP‐3 and MMP‐13 expression with phosphorylation of IκB kinase complex in response to IL‐1β stimulation, whereas treatment with a specific p‐IκB kinase inhibitor attenuated MMP‐3 and MMP‐13 expression. Our results indicated that p21‐deficient DMM mice were susceptible to alterations in OA phenotype, including enhanced osteoclast expression, macrophage infiltration, and MMP expression through IL‐1β‐induced NF‐κB signaling, suggesting that p21 regulation may constitute a possible therapeutic strategy for OA treatment. © 2017 American Society for Bone and Mineral Research.     

A Palmar Fracture-Dislocation of the Proximal Interphalangeal Joint of the Middle Finger Caused by Bowling: A Case Report

During bowling, a twenty year old man could not pull out his middle finger from the ball in release and injured his finger. X-ray revealed a palmar fracture- dislocation of the PIP joint. We manipulated the PIP joint, but a gap remained at the fracture site on the X-ray after reduction. Surgical treatment was performed with a screw. Postoperatively, the middle finger was fixed with a splint for two weeks, and then active range of motion exercises were started. One year after the operation, the fracture had healed with a congruous joint surface, and the patient had full range of motion in the middle finger with no difficulties in activities of daily living. The etiology of a palmar fracture-dislocation of the PIP joint is still controversial, but we suggested the mechanism of the fracture-dislocation was caused by a shearing force to the middle phalangeal base from a dorsal direction. The main cause of the current injury was the poor fit between the middle finger and the hole of the bowling ball. Bowling is a popular and safe sport, but we should be aware of unexpected hand injuries related to bowling which may occur, especially in players at a recreational level.

Key points

• We presented a palmar fracture-dislocation of the PIP joint in a middle finger that occured while bowling.
• We discussed the mechanism and suggested the main cause of the injury was the poor fit between the middle finger and the hole of the bowling ball.
• We advised that while bowling is recognized as a safe sport, due to its popularity we should be aware of unexpected hand injuries which may occur, especially in players at a recreational level.

Key words: Palmal fracture-dislocation, PIP joint, bowling, sports