Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2

ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected.     

Health status of the over 60 years of age population and its relationship with sociodemographic factors (ANCO Project)

OBJECTIVE: To describe the health status of a population over 60 years and to study their relationship with several socio-demographic variables. DESIGN: A cross-sectional study, population based. SETTINGS: A community. PARTICIPANTS: A randomized sample of 1,103 non institutionalized people over 60 years living in the city of Cordoba (Spain). MEASUREMENTS AND MAIN RESULTS: By mean of a personal interview at home we used the OARS-MFAQ-VE questionnaire. Low self-rated health was associated with the age, to be female sex, a low cultural background, and a low income. Only 5.2% of the study people do not suffered any illness and 56% state that their health problems are major problems for doing their current activities. 4.9% declared to have some degree of physical incapacity. 3.7% of elderly population has an important cognitive deficit. CONCLUSIONS: The majority of elderly people has good health. Age is related with a poor health. Women have more health problems than men.     

Sympathetic nervous system activity and resting metabolic rate in vegetarians

We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.     

Maxillary sinus augmentation in the non-human primate: a comparative radiographic and histologic study between recombinant human osteogenic protein-1 and natural bone mineral

The posterior maxilla has traditionally been one of the most difficult areas to successfully place dental implants due to poor bone quality and close approximation to the maxillary sinus. Sinus augmentation procedures have become a viable means of assuring adequate bone for the placement of dental implants in this area. However, with the techniques currently employed, a considerable variation in the quality of bone attained with the sinus augmentation procedure exists. The purpose of this in vivo study was to evaluate the healing response and bone formation stimulated by 3 doses of recombinant human osteogenic protein-1 (rhOP-1), 0.25, 0.6, and 2.5 mg OP-1 per gram of collagen matrix; natural bone mineral; or collagen matrix alone (control) placed in the maxillary sinus of adult chimpanzees. Results were assessed using clinical, histologic, and radiographic techniques. Radiographic analysis of the computed tomography scans taken at 1 week, and 2.5, 4.5, and 6.5 months revealed a more rapid mineralization with the 2.5 mg OP-1/g collagen matrix and natural bone mineral treatment groups. The incremental bone mineral density (BMD) increase for these 2 treatments from 1 week to 2.5 months was over 2.5 times the increase found with the collagen matrix alone; these 2 treatments also had a higher BMD at the most superior slices evaluated when compared to the other 3 groups. Biopsy specimens were taken at 3.5, 5.5, and 7.5 months and for all 5 treatment groups bone formation was observed at all time points in the majority of the specimens. At 7.5 months the 2.5 and 0.6 mg OP-1/g collagen matrix treatment groups had an increase in the percent bone area when compared to the matrix alone control. In conclusion, these results demonstrate that sinus augmentation with natural bone mineral or 2.5 mg OP-1/g collagen matrix induce comparable radiographic and histologic evidence of bone formation and that both of these treatments performed superior to the control group of collagen matrix alone based upon all methods of evaluation.     

Adaptive Spatial Partitioning for Multidimensional Data Streams

We propose a space-efficient scheme for summarizing multidimensional data streams. Our sketch can be used to solve spatial versions of several classical data stream queries efficiently. For instance, we can track ε-hot spots, which are congruent boxes containing at least an ε fraction of the stream, and maintain hierarchical heavy hitters in d dimensions. Our sketch can also be viewed as a multidimensional generalization of the ε-approximate quantile summary. The space complexity of our scheme is O((1/ε) log R) if the points lie in the domain [0, R]^d, where d is assumed to be a constant. The scheme extends to the sliding window model with a log (ε n) factor increase in space, where n is the size of the sliding window. Our sketch can also be used to answer ε-approximate rectangular range queries over a stream of d-dimensional points.