IMPACT SHOULDER ANGLES CORRELATE WITH IMPACT WRIST ANGLES IN STANDING BACK HANDSPRINGS IN PREADOLESCENT AND ADOLESCENT FEMALE GYMNASTS.

BACKGROUND AND PURPOSE: In gymnastics, the wrist is exposed to many different stresses including increased extension, especially during back handsprings. Currently a wrist extension angle during impact that places the wrist in danger has not been established. The purpose of this study was to: (1) determine the mean impact wrist angle during a standing back handspring in female preadolescent and adolescent gymnasts and (2) determine which factors predict impact wrist angles. METHODS: Fifty female gymnasts from six facilities, ages 8-15 were included in this study. Each gymnast completed a questionnaire about gymnastics participation and history of wrist pain. Active range of motion of the shoulder, elbow, wrist, hip, and ankle was measured. Each gymnast was asked to perform a standard back handspring, which was videotaped. The wrist and shoulder flexion angles, at maximum impact, were recorded and measured using motion analysis software. Two-sample t-test was used to assess the relationship between impact wrist angle and wrist pain. Multiple linear regression was used to determine the association between related variables and impact wrist angle. RESULTS: The mean back handspring impact wrist angle was 95°. Fifteen subjects (30%) reported wrist pain. Years of participation (p=0.02) and impact shoulder angle (p=0.04) were predictive of impact wrist angles. CONCLUSION: Shoulder angles and years of participation correlate with impact wrist angles during the performance of a standing back handspring. Future studies are necessary to determine if addressing these factors can affect the impact wrist angles. LEVEL OF EVIDENCE: 3.

Where do we go from here? An inside look into the development of Georgia's Youth Concussion Law.

Currently, all 50 states and the District of Columbia have youth concussion laws based on the core principals of the 2009 Lystedt Law of Washington State. On April 23, 2013, the state of Georgia signed into law House Bill 284, "The Return to Play Act of 2013" and became one of the last states to pass youth concussion legislation. This Act became effective on January 1, 2014. The purpose of this report is to highlight the legislative process of enacting Georgia House Bill 284 and compare it to the legislation of other states.

Pediatric sports specific return to play guidelines following concussion.

PURPOSE/BACKGROUND: In 2010, the American Academy of Pediatrics officially adopted the recommended return to play guidelines proposed by the International Conference on Concussion in Sport. The guidelines include a six-step process that provides structure to guide an athlete who is recovering from a concussion in a gradual return to play (RTP) by allowing participation in increasingly difficult physical activities. Unfortunately, the guidelines fail to take into account the variability that occurs within different sports and the resulting challenges medical professionals face in making sure each athlete is able to withstand the rigors of their specific sport, without return of symptoms. Therefore, the purpose of this clinical commentary is to expand upon the current general consensus guidelines for treatment of concussed pediatric athletes and provide sport specific RTP guidelines. DESCRIPTION OF TOPIC: The intention of the sport specific guidelines is to maintain the integrity of the current six-step model, add a moderate activity phase highlighted by resistance training, and to provide contact and limited contact drills specific to the athlete's sport and/or position. The drills and activities in the proposed seven-step programs are designed to simulate sport specific movements; the sports include: football, gymnastics, cheerleading, wrestling, soccer, basketball, lacrosse, baseball, softball, and ice hockey. These activities will provide sports specific challenges to each athlete while simultaneously accomplishing the objectives of each stage of the RTP progression. The final RTP determination should occur with documented medical clearance from a licensed healthcare provider who has been trained in the evaluation and management of concussions. DISCUSSION/RELATION TO CLINICAL PRACTICE: There have been significant strides in the management and care of concussed athletes. However, there continues to be a lot of confusion among, athletes, parents, and coaches regarding the proper management of an athlete with a concussion, particularly in the pediatric population. In an effort to eliminate ambiguity and help further promote adherence to the RTP guidelines, the authors developed several sports-specific RTP guidelines. LEVEL OF EVIDENCE: 5.

Failure analysis of knee arthrodesis with the WichitaFusion Nail.

Arthrodesis is a salvage procedure for failed total knee arthroplasty with the intent to create a stable, pain-free limb on which to ambulate or transfer. For many patients, the alternative to arthrodesis may be an above-knee amputation. Available techniques for knee arthrodesis include compression plating, external fixators, and intramedullary fixation. The purpose of this study was to report the knee fusion rate of consecutive patients at 1 institution using an intramedullary fusion nail and to identify patient risk factors for fusion failure. Between November 1998 and November 2008, twenty-eight patients undergoing knee arthrodesis with an average follow-up of 18 months (range, 3-64 months) were retrospectively studied. Demographic information, presence of fusion, clinical function, pain level, and bone defect data were collected and analyzed. Eighty-two percent (23/28) of patients had radiographic evidence of successful fusion with an average time to fusion of 21 weeks (range, 10-58 weeks). When examining patient variables that could correlate with fusion rates, patients with an Anderson Orthopaedic Research Institute type 3 femoral or type 3 tibial defect had a statistically significant lower fusion rate. The intramedullary fusion nail is an effective device for knee arthrodesis that offers ease of insertion through the knee wound with the advantages of initial bone compression and rigid fixation. Although the use of intramedullary fusion nails leads to a high fusion rate, significant bone deficiency limits successful fusion.

Five- to ten-year outcomes for modular metal-on-metal total hip arthroplasty.

In recent years, metal-on-metal (MOM) arthroplasty has come under fire with reported adverse outcomes of metal hypersensitivity, adverse local tissue reaction (ALTR), and the carcinogenicity concern from systemic metal ions. We present a retrospective analysis of 354 primary total hip arthroplasties from 2 independent centers. Revision data, predicted survival and Harris Hip Scores (HHS) are reported. Nine hips (2.5%) underwent component revision, and 9 year predicted survival was 95.8%. One revision had elevated metal ions but no histological evidence of ALTR. Average HHS at a minimum 5 year follow up (range 5-10 years) improved significantly from 52 pre-operatively to 93 post-operatively. While a 2.5% revision rate and improved clinical outcomes are reported in this study, longer term follow-up is warranted to monitor for late complications.

Sensory neuropathy associated with aggressive cauterization using a bipolar radiofrequency device in primary TKA.

Because significant postoperative blood loss can result in many complications, hemostasis remains a critical part of successful joint replacement outcomes. Advanced techniques, such as electrocautery use after optimally timed tourniquet release, focus on desired patient blood loss outcomes. The purposes of this study were to report the incidence of nerve injury, identify associated risk factors following the use of bipolar electrocautery for hemostasis in the posterior knee during primary total knee arthroplasty, and compare that rate with the rate seen using a standard electrocautery device. Clinical and operative data were retrospectively reviewed for an association with postoperative nerve injury in 241 consecutive patients when using bipolar electrocautery between July 2007 and October 2008. A comparison group of 192 demographically similar consecutive patients between November 2008 and October 2009 was also evaluated to establish a surgeon-specific benchmark when using standard electrocautery. Seven (2.9%) of 241 patients in the bipolar electrocautery group reported documented neuropathies compared with 1 (0.52%) of 192 patients using standard electrocautery. In addition, female sex and rheumatoid arthritis were associated with postoperative nerve injury following bipolar electrocautery. Although the bipolar radiofrequency device is effective in achieving hemostasis, the authors recommend judicious use of this procedure in women or patients with rheumatoid arthritis and cautious, nonaggressive use of posterior compartment bipolar radiofrequency ablation in the remaining patient populations.

Articulating spacers for the treatment of infected total knee arthroplasty: effect of antibiotic combinations and concentrations.

Performing 2-stage procedures using articulating antibiotic cement spacers to eradicate infection while providing pain relief and maintaining function has become common among many surgeons. Despite the efficacy of antibiotic cement spacers in the treatment of infected total knee arthroplasty, questions remain regarding the dosing of the antibiotic cement. The authors assessed their experience with different antibiotic regimens and concentrations for the eradication of infection. Sixty-nine infected total knee arthroplasties with an average follow up of 31 months (range, 6-70 months) treated with articulating antibiotic spacers were retrospectively reviewed. Treatment groups were divided according to spacer antibiotic agents used and the amount of antibiotics added to the cement. Low-dose spacers were defined as those incorporating less than 4 g of antibiotic per 40-g bag of cement, and high-dose spacers were defined as those incorporating 4 g or more of antibiotic per 40-g bag of cement. High- vs low-dose spacers using a single or multiple antibiotic agents were compared. The overall rate of infection eradication was 88%. Dose dependency was not detected for spacers that incorporated single or multiple antibiotic agents, and multiple-agent spacers produced comparable success rates despite more frequent use in patients with impaired immune function. Further study of optimal combinations and concentrations of antibiotic agents incorporated into these spacers is needed to help minimize treatment failures while maximizing treatment efficacy.

Minimally invasive surgery through endoscopic laminotomy and foraminotomy for the treatment of lumbar spinal stenosis.

BACKGROUND: Lumbar spinal stenosis is a common cause of radicular and generalized back pain among older adults. Endoscopic minimally invasive surgery, in contrast to open decompression, may provide the opportunity for a less invasive surgical intervention. Thus, the purpose of this study is to evaluate the safety (operative complications, estimated blood loss, operative room time) and effectiveness (pre- versus postoperative level of disability and pain severity) of minimally invasive surgery using endoscopic laminotomy and foraminotomy among a large sample of patients with lumbar spinal stenosis. METHODS: This study is composed of 320 consecutive patients with lumbar spinal stenosis who underwent posterior lumbar laminotomy and foraminotomy between 2008 and 2011. Outcome measures consisted of perioperative complications, estimated blood loss, operative room time, level of disability, and pain severity. Pain severity and level of disability were prospectively analyzed to an average of 18 months (12-36 months) post-surgery. RESULTS: There was an average estimated blood loss of 39.3 cc and a mean operative room time of 74 min. Seven patients experienced minor operative complications. All patients were discharged the same day as surgery and reported a significantly lower level of disability (p = 0.00) and pain severity (p = 0.00) postoperative compared to preoperative. CONCLUSIONS: Minimally invasive surgery using endoscopy for the treatment of lumbar spinal stenosis has a short operative time, a low operative complication rate, and minimal estimated blood loss. This study also indicates that MIS for the treatment of LSS can significantly reduce pain and disability level. Thus, minimally invasive surgery using endoscopic laminotomy and foraminotomy appears to be a safe and effective alternative surgical treatment for open decompression surgery in adult patients with lumbar spinal stenosis.

Cost analysis in shoulder arthroplasty surgery.

Cost in shoulder surgery has taken on a new focus with passage of the Patient Protection and Affordable Care Act. As part of this law, there is a provision for Accountable Care Organizations (ACOs) and the bundled payment initiative. In this model, one entity would receive a single payment for an episode of care and distribute funds to all other parties involved. Given its reproducible nature, shoulder arthroplasty is ideally situated to become a model for an episode of care. Currently, there is little research into cost in shoulder arthroplasty surgery. The current analyses do not provide surgeons with a method for determining the cost and outcomes of their interventions, which is necessary to the success of bundled payment. Surgeons are ideally positioned to become leaders in ACOs, but in order for them to do so a methodology must be developed where accurate costs and outcomes can be determined for the episode of care.

Complications following distal biceps repair.

PURPOSE: Distal biceps rupture is a relatively uncommon injury. Surgical repair is performed in patients who seek increased flexion and supination strength over that which results from nonoperative treatment. The purpose of this study was to evaluate complications associated with surgical repair of the distal biceps tendon in a large series of patients. METHODS: We retrospectively reviewed 198 consecutive patients with distal biceps ruptures treated with surgical repair, and evaluated time from injury to repair, surgical technique, and complications. RESULTS: A total of 72 patients (36%) developed complications; 6 patients underwent additional surgery. Minor complications included lateral antebrachial cutaneous nerve paresthesia (26%), radial sensory nerve paresthesia (6%), and superficial infection (2%). Major complications included posterior interosseous nerve injury (4%), symptomatic heterotropic ossification (3%), and re-rupture (2%). CONCLUSIONS: Minor complications were common after distal biceps tendon repair; however, most were sensory nerve injuries that resolved with time. Major complications were infrequent, and few patients required revision surgery. Complications were more common after distal biceps tendon repair performed more than 28 days after rupture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Clinical outcomes of total wrist arthroplasty.

PURPOSE: Current indications for total wrist arthroplasty include patients with symptomatic end stage posttraumatic wrist arthritis, rheumatoid arthritis, and Kienböck disease, as an alternative to wrist arthrodesis. Arthroplasty may have advantage over arthrodesis because of the ability to retain motion. The purpose of this study was to evaluate the short-term clinical outcomes and complications of the Maestro Total Wrist System. METHODS: We report the results of a retrospective review of 23 total wrist prostheses implanted in 22 patients. We administered the visual analog pain scale and Mayo wrist and Disabilities of the Arm, Shoulder, and Hand questionnaires. We reviewed wrist motion, grip strength, radiographs, and complications. RESULTS: At a mean follow-up of 28 months (range, 4-55 mo), the Disabilities of the Arm, Shoulder, and Hand score and Mayo wrist score were 31 and 54, respectively. Mean pain scores improved from 8.0 to 2.2. The mean wrist flexion-extension arc was 90°. Radiographs revealed no evidence of prosthetic loosening. Grip strength averaged 60% of the strength of the opposite hand. Complications occurred in 7 of 23 patients. One failure occurred as a result of deep infection in a patient with prior intercarpal fusion, and was successfully converted to a wrist fusion. CONCLUSIONS: Total wrist arthroplasty performed for pancarpal arthritis as an alternative to wrist arthrodesis can yield successful outcomes with low short-term failure rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Proximal row carpectomy with capitate osteochondral autograft transplantation.

Proximal row carpectomy (PRC) is an effective treatment option for degenerative or posttraumatic osteoarthritis of the wrist in conditions such as scapholunate advanced collapse, scaphoid nonunion advanced collapse, Kienbock disease, and chronic fracture dislocations of the carpus. PRC involves excision of the scaphoid, lunate, and triquetrum, and relies on the articulation of the remaining capitate from the distal row to articulate with the lunate fossa. PRC offers the potential advantage of greater range of motion, technical ease, and decreased immobilization, and eliminates specific complications found with other motion-preserving procedures such as nonunion, hardware irritation, and impingement. An established relative contraindication for PRC is the presence of advanced capitolunate arthritis. Many authors have offered modifications of the traditional PRC procedure to account for the presence of capitate arthritis. A PRC technique utilizing an osteochondral autograft, from the carpal bank of excised bones, for transfer to the capitate defect is described.

Effect on blood loss and cost-effectiveness of pain cocktails, platelet-rich plasma, or fibrin sealant after total knee arthroplasty.

UNLABELLED: This study evaluated the effect of periarticular pain cocktail, platelet-rich plasma, or fibrin sealant injections on blood loss, transfusion rate, and hospital costs after total knee arthroplasty. A retrospective review of 400 patients undergoing primary total knee arthroplasty with one of the different periarticular treatments as stated above was performed. Postoperative blood loss, hemoglobin levels, allogenic blood transfusion rates, and per-case hospital injection cost were reported. Although platelet-rich plasma and fibrin sealant decreased blood loss compared with the control group (P < .001), there was no significant difference in blood loss in the pain-cocktail group or in postoperative hemoglobin levels or transfusion rates between all groups. Significant efficacy and cost-effectiveness for these modalities could not be identified and have, therefore, been discontinued at our practice. LEVEL OF EVIDENCE: level III.

Chronic ethanol ingestion increases aortic endothelial nitric oxide synthase expression and nitric oxide production in the rat.

BACKGROUND: Chronic alcohol consumption perturbs cellular function in a variety of organ systems. Previous studies have suggested that moderate alcohol consumption reduces vascular disease, whereas heavier alcohol consumption may worsen it. The mechanisms for these vascular effects of chronic alcohol ingestion continue to be defined and constitute the focus of this study. METHODS: Male Sprague Dawley rats were fed an isocaloric, Lieber-Decarli liquid diet containing either ethanol (36% calories) or Maltose-Dextrin (substituted for ethanol) for 6 weeks. Telemetric blood pressure measurements were taken before and after ethanol feeding. After the rats were killed, the aortas were analyzed for endothelial nitric oxide (NO) synthase expression and NO production. RESULTS: Chronic ethanol ingestion decreased mean arterial pressure and increased aortic NO production as demonstrated by direct ex vivo measurements using iron diethyldithio-carbamic acid as well as analysis of nitrosyl-hemoglobin (NO-Hb) levels. Consistent with these assays of vascular NO production, endothelium-dependent relaxation responses to acetycholine (Ach) were enhanced in ethanol-fed animals. Aortic endothelial nitric oxide synthase expression was also increased by chronic ethanol ingestion. CONCLUSIONS: These findings demonstrate that a regimen of chronic alcohol ingestion in the rat produced generally salutary effects in the systemic vasculature following a 6-week treatment regimen. These findings extend previous in vitro studies to demonstrate that alcohol has potent effects on vascular endothelial nitric oxide synthase expression, NO production, and vascular function. Consistent with previous reports, these findings confirm that alcohol-induced alterations in the production of reactive nitrogen species play an important role in the pathogenesis of alcohol-mediated tissue effects.

Chronic ethanol ingestion increases nitric oxide production in the lung.

Chronic ethanol (EtOH) ingestion increases the incidence of acute respiratory distress syndrome. The mechanisms underlying EtOH-induced susceptibility to lung injury continue to be defined. This study examines the hypothesis that EtOH increases endothelial nitric oxide synthase (eNOS) expression and activity in the lungs of a rat model of chronic EtOH ingestion. Male Sprague-Dawley rats were fed liquid diets containing EtOH (36% of calories) or maltose-dextrin as an isocaloric substitution for EtOH (control) for 6 weeks. Selected animals were also treated with the angiotensin-converting enzyme (ACE) inhibitor lisinopril (3 mg/l in diet) for 6 weeks. At study completion, animals were sacrificed, and lung tissue was collected for assays of nitric oxide (NO) metabolism or pulmonary microvascular endothelial cells (MVEC) were isolated for analysis of NO release. Compared to the control diet, chronic EtOH ingestion increased lung H2O2 production, eNOS expression and activity, lung cyclic guanosine monophosphate (cGMP) content, and levels of protein nitration and oxidation. MVEC from animals with chronic EtOH ingestion released greater amounts of NO. EtOH-induced increases in lung H2O2 production, eNOS expression and activity, cGMP content, protein nitration and oxidation, and MVEC NO production were all attenuated by treatment with lisinopril. Chronic EtOH ingestion stimulates ACE-dependent increases in NO production in the lung. These novel findings indicate that chronic EtOH ingestion increases reactive species production in the lung parenchyma and provide new insights into mechanisms by which EtOH causes phenotypic alterations in the lung and alters the lung's response to inflammatory stimuli.

Chronic ethanol ingestion increases superoxide production and NADPH oxidase expression in the lung.

Alcohol abuse increases the incidence of acute respiratory distress syndrome and causes oxidative stress and cellular dysfunction in the lung. The mechanisms of ethanol (EtOH)-induced oxidative stress in the lung remain to be defined. Chronic alcohol ingestion has been associated with increased renin-angiotensin system (RAS) activity. Therefore, the current study investigated the ability of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, to modulate oxidative stress in the lung after chronic EtOH ingestion in a well-established rat model. Male Sprague-Dawley rats were fed liquid diets containing EtOH (36% of calories) or maltose-dextrin as an isocaloric substitution for EtOH (Control) for 6 wk. Selected animals were also treated with lisinopril (3 mg/liter) for 6 wk. Chronic EtOH ingestion increased bronchoalveolar lavage fluid glutathione disulfide levels and superoxide formation in lung parenchyma. These effects of EtOH were attenuated by lisinopril treatment. Chronic EtOH ingestion failed to increase ACE expression or angiotensin II levels in lung homogenates, but increased angiotensinogen, angiotensin II type 1 and type 2 receptor levels, and ACE activity. Chronic EtOH ingestion also increased the levels of the NADPH oxidase subunit, gp91phox, an effect that was attenuated by lisinopril, but had no effect on lung p22phox or p47phox levels. These findings suggest that EtOH-mediated RAS activation plays an important role in pulmonary oxidative stress and provide new insights into mechanisms by which EtOH causes oxidative stress in the lung and potential strategies of lung protection through ACE inhibition.

Chronic ethanol exposure stimulates endothelial cell nitric oxide production through PI-3 kinase-and hsp90-dependent mechanisms.

BACKGROUND: Chronic ethanol (EtOH) ingestion increases the incidence of the Acute Respiratory Distress Syndrome (ARDS), a severe form of acute lung injury characterized by endothelial and epithelial barrier dysfunction. The regulated production of nitric oxide (NO) by the endothelium plays a central role in normal vascular function, and alterations in NO production have been implicated in barrier dysfunction. Although previous reports examined the impact of acute EtOH stimulation on endothelial NO production, this study extends those observations to clarify mechanisms of chronic EtOH-mediated alterations in endothelial nitric oxide synthase (eNOS) expression and NO production. METHODS: Porcine pulmonary artery endothelial cells (PAEC) were treated with EtOH (0.04-0.16%, w/v) for 72 hr in sealed chambers to prevent evaporation. NO release and eNOS expression were determined to examine the effect of chronic EtOH stimulation on endothelial NO metabolism. RESULTS: While there was no change in the extent of phosphorylated eNOS at ser, chronic EtOH stimulation caused dose-dependent increases in NO production and increased eNOS expression, effects that were attenuated by the transcriptional inhibitor, alpha-amanitin (AA), and wortmannin, a specific phosphatidylinositol 3 kinase (PI3 K) inhibitor. EtOH stimulation also increased eNOS interaction with heat shock protein (hsp90), a molecular chaperone known to enhance eNOS activity. Geldanamycin, an hsp90 inhibitor, attenuated chronic EtOH-mediated increases in NO production. CONCLUSIONS: These results indicate that chronic EtOH exposure increases endothelial NO production by increasing eNOS protein levels through PI3 K-dependent up regulation of eNOS gene transcription and by increasing interactions between eNOS and hsp90. These findings clarify mechanisms by which chronic EtOH stimulation modulates vascular endothelial function and suggest new targets for investigation and intervention in EtOH-induced alterations in susceptibility to lung injury.

YB-1 coordinates vascular smooth muscle alpha-actin gene activation by transforming growth factor beta1 and thrombin during differentiation of human pulmonary myofibroblasts.

Profibrotic regulatory mechanisms for tissue repair after traumatic injury have developed under strong evolutionary pressure to rapidly stanch blood loss and close open wounds. We have examined the roles played by two profibrotic mediators, transforming growth factor beta1 (TGFbeta1) and thrombin, in directing expression of the vascular smooth muscle alpha-actin (SMalphaA) gene, an important determinant of myofibroblast differentiation and early protein marker for stromal cell response to tissue injury. TGFbeta1 is a well known transcriptional activator of the SMalphaA gene in myofibroblasts. In contrast, thrombin independently elevates SMalphaA expression in human pulmonary myofibroblasts at the posttranscriptional level. A common feature of SMalphaA up-regulation mediated by thrombin and TGFbeta1 is the involvement of the cold shock domain protein YB-1, a potent repressor of SMalphaA gene transcription in human fibroblasts that also binds mRNA and regulates translational efficiency. YB-1 dissociates from SMalphaA enhancer DNA in the presence of TGFbeta1 or its Smad 2, 3, and 4 coregulatory mediators. Thrombin does not effect SMalphaA gene transcription but rather displaces YB-1 from SMalphaA exon 3 coding sequences previously shown to be required for mRNA translational silencing. The release of YB-1 from promoter DNA coupled with its ability to bind RNA and shuttle between the nucleus and cytoplasm is suggestive of a regulatory loop for coordinating SMalphaA gene output in human pulmonary myofibroblasts at both the transcriptional and translational levels. This loop may help restrict organ-destructive remodeling due to excessive myofibroblast differentiation.

Peroxisome proliferator-activated receptor gamma ligands stimulate endothelial nitric oxide production through distinct peroxisome proliferator-activated receptor gamma-dependent mechanisms.

OBJECTIVE: We recently reported that the peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) and ciglitazone increased cultured endothelial cell nitric oxide (NO) release without increasing the expression of endothelial nitric oxide synthase (eNOS). The current study was designed to characterize further the molecular mechanisms underlying PPARgamma-ligand-stimulated increases in endothelial cell NO production. METHODS AND RESULTS: Treating human umbilical vein endothelial cells (HUVEC) with PPARgamma ligands (10 micromol/L 15d-PGJ2, ciglitazone, or rosiglitazone) for 24 hours increased NOS activity and NO release. In selected studies, HUVEC were treated with PPARgamma ligands and with the PPARgamma antagonist GW9662 (2 micromol/L), which fully inhibited stimulation of a luciferase reporter gene, or with small interfering RNA to PPARgamma, which reduced HUVEC PPARgamma expression. Treatment with either small interfering RNA to PPARgamma or GW9662 inhibited 15d-PGJ2-, ciglitazone-, and rosiglitazone-induced increases in endothelial cell NO release. Rosiglitazone and 15d-PGJ2, but not ciglitazone, increased heat shock protein 90-eNOS interaction and eNOS ser1177 phosphorylation. The heat shock protein 90 inhibitor geldanamycin attenuated 15d-PGJ2- and rosiglitazone-stimulated NOS activity and NO production. CONCLUSIONS: These findings further clarify mechanisms involved in PPARgamma-stimulated endothelial cell NO release and emphasize that individual ligands exert their effects through distinct PPARgamma-dependent mechanisms.