Endothelial catabolism of extracellular adenosine during hypoxia: the role of surface adenosine deaminase and CD26

Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. Functional studies of murine hypoxia revealed inhibition of ADA with deoxycoformycin (dCF) enhances protective responses mediated by adenosine (vascular leak and neutrophil accumulation). Analysis of plasma ADA activity in pediatric patients with chronic hypoxia undergoing cardiac surgery demonstrated a 4.1 +/- 0.6-fold increase in plasma ADA activity compared with controls. Taken together, these results reveal induction of ADA as innate metabolic adaptation to chronically elevated adenosine levels during hypoxia. In contrast, during acute hypoxia associated with vascular leakage and excessive inflammation, ADA inhibition may serve as therapeutic strategy.     

Red wine polyphenols do not improve obesity‐associated insulin resistance: A randomized controlled trial

Preclinical studies have suggested that polyphenols extracted from red wine (RWPs) favourably affect insulin sensitivity, but there is controversy over whether RWPs exert similar effects in humans. The aim of the present study was to determine whether RWPs improve insulin sensitivity in obese volunteers. Obese (body mass index >30 kg/m²) volunteers were randomly allocated to RWPs 600 mg/d (n = 14) or matched placebo (n = 15) in a double‐blind parallel‐arm study for 8 weeks. The participants were investigated at baseline and at the end of the study. Insulin sensitivity was determined using a hyperinsulinaemic‐euglycaemic clamp (M‐value), a mixed‐meal test (Matsuda index), and homeostatic model assessment of insulin resistance (HOMA‐IR). RWPs elicited no significant changes in M‐value (RWP group: median [interquartile range; IQR] baseline 3.0 [2.4; 3.6]; end of study 3.3 [2.4; 4.8] vs placebo group: median [IQR] baseline 3.4 [2.8; 4.4]; end of study 2.9 [2.8; 5.9] mg/kg/min; P = .65), in Matsuda index (RWP group: median [IQR] baseline 3.3 [2.2; 4.8]; end of study 3.6 [2.4; 4.8] vs placebo group: median [IQR] baseline 4.0 [3.0; 6.0]; end of study 4.0 [3.0; 5.2]; P = .88), or in HOMA‐IR. This study showed that 8 weeks of RWP supplementation did not improve insulin sensitivity in 29 obese volunteers. Our findings were not consistent with the hypothesis that RWPs ameliorate insulin resistance in human obesity.     

Optimal Design of Ferronickel Slag Alkali-Activated Material for High Thermal Load Applications Developed by Design of Experiment

The development of an optimal low-calcium alkali-activated binder for high-temperature stability based on ferronickel slag, silica fume, potassium hydroxide, and potassium silicate was investigated based on Mixture Design of Experiment (Mixture DOE). Mass loss, shrinkage/expansion, and compressive and flexural strengths before and after exposure to a high thermal load (900 °C for two hours) were selected as performance markers. Chemical activator minimization was considered in the selection of the optimal mix to reduce CO₂ emissions. Unheated 42-day compressive strength was found to be as high as 99.6 MPa whereas the 42-day residual compressive strength after exposure to the high temperature reached 35 MPa (results pertaining to different mixes). Similarly, the maximum unheated 42-day flexural strength achieved was 8.8 MPa, and the maximum residual flexural strength after extreme temperature exposure was 2.5 MPa. The binder showed comparable properties to other alkali-activated ones already studied and a superior thermal performance when compared to Ordinary Portland Cement. A quantitative X-ray diffraction analysis was performed on selected hardened mixes, and fayalite was found to be an important component in the optimal formulation. A life-cycle analysis was performed to study the CO₂ savings, which corresponded to 55% for economic allocation.     

Cross-national variation of gender differences in adolescent subjective health in Europe and North America

The cross-national consistency and variation of gender differences in subjective health complaints was examined in a sample of 125732 11- to 15-year-olds from 29 European and North American countries, participating in the WHO collaborative study 'Health behaviour in school-aged children (HBSC) 1997/98'. Health complaints were measured with the Health Behaviour in School-aged Children Symptom Checklist. Gender differences in health complaints were analysed through multilevel logistic regression analysis. The results indicated a very robust pattern of increasing gender differences across age, with 15-year-old girls as a group at increased risk for health complaints across all countries. The magnitude of gender differences varied across countries, with some countries showing a consistently strong gender difference across age group and different health complaints, and other countries showing a consistently weak gender difference. The gender difference in health complaints was stronger in countries with a low gender development index score. The findings underscore the need to incorporate socio-contextual factors in the study of gender health inequalities during adolescence.     

Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience

PURPOSE: To assess the clinical results of spot scanning proton beam radiation therapy (PT) in the treatment of skull base chordomas and low-grade chondrosarcomas (CS). METHODS AND MATERIALS: Between October 1998 and October 2003, 29 patients (median age, 39 years) with chordomas (n = 18) and CS (n = 11) were treated at the Paul Scherrer Institut (PSI) with protons using the main 510-MeV cyclotron. Tumor conformal application of proton beams was realized by spot scanning technology. The median chordoma and CS dose was 74 and 68 cobalt Gy equivalent, respectively (cobalt Gy equivalent = proton Gy x 1.1). Median gross tumor volumes (GTV) were 16.4 mL (range, 1.8-48.1 mL) and 15.2 mL (range, 2.3-57.3 mL) for chordoma and CS, respectively. Late toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system. The median follow-up time was 29 months (range, 6-68 months). RESULTS: Actuarial 3-year local control rates were 87.5% and 100% for chordoma and CS, respectively. We observed one surgical pathway and one marginal failure in patients with chordomas. No regional failure or distant metastasis was observed. At 3 years, actuarial PFS and OS for the entire cohort was 90% and 93.8%, respectively. Actuarial 3-year complication-free survival was 82.2%. Radiation-induced pituitary dysfunction was observed in 4 (14%) patients (CTCAE Grade 2). No patient presented with post-PT brainstem or optic pathways necrosis or dysfunction. In univariate analysis, age < or =40 years at the time of PT affected favorably on PFS (p = 0.09). CONCLUSION: Spot-scanning PT offers high tumor control rates of skull base chordoma and CS. These results compare favorably to other combined proton-photon or carbon ion irradiation series. Observed toxicity was acceptable. Younger age (< or =40 years) was a favorable prognostic factor of PFS. These preliminary results are encouraging but should be confirmed during a longer follow-up.     

Patient satisfaction, function and return to work after knee arthroplasty

We investigated the working status during 2 years before and 2 years after primary knee prosthetic operation for arthrosis in order to identify preoperative factors predicting patient satisfaction, function and working capacity. 162 patients (86 women) younger than 60 years of age when operated on with a knee prosthesis during 1993 were studied. 91% of the patients returned a Nottingham Health Profile (NHP) questionnaire, and the Social Insurance Office could supply data on all patients. There was a positive association between the duration of pre- and postoperative sick-leave in the patients who returned to work. Preoperative sick-leave longer than 180 days increased the risk of postoperative disability pension, which was not found to be influenced by the grade of the work. Among the 52 patients who returned to work postoperatively, all 6 NHP functional categories were better in the patients with less than 180 days of preoperative sick-leave than in the patients with more than 180 days of preoperative sick-leave. The overall patient satisfaction was greater among patients who went back to work postoperatively. We conclude that long sick-leave before a knee prosthetic operation increases the risk of long postoperative sick-leave and disability pension and impairs the quality of life.     

Subacute Left Ventricular Free Wall Rupture

In a 59-year-old man, Left ventricular free wall rupture following acute myocardial infarction was diagnosed by transthoracic echocardiography, left ventriculography and a combination of saline injection into the left ventricle and concomitant transthoracic echocardiography. The Operation was successfully performed with an extracorporeal bypass on the beating heart. Some technical aspects of the treatment are discussed.