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.     

Properties of Carbopol Solutions as Models for Yield-Stress Fluids

ABSTRACT: The effect of pH on the non-Newtonian viscosity (η)of aqueous Carbopol 940 solutions is presented with high resolution (pH increments about 0.4) between pH = 2.8 and 12.7. Aqueous NaOH was used to adjust pH of 1.48 wt % Carbopol solutions. A Contraves viscometer was used to measure steady-flow shear stress at known shear rate (γ) over the range γ= 8 to 195 s⁻¹. Yield stresses and shear-thinning η(γ) were observed. Data were fitted with a Herschel-Bulkley model, whose parameters (including yield stress) were expressed as functions of pH. Comparisons were made of η(γ) to the dynamic viscometric properties η'(ω) and η*(ω) for comparable ranges of γ and frequency (ω): A fairly close match was found between η and η* but η«η'. pH dependence included previously unreported extrema of h(pH) in the range of pH = 6.2 to 6.6. Because of sensitive control of rheological properties with pH, Carbopol solutions can be used to mimic a great range of shear-thinning and yield-stress behavior that should make them useful for model studies directed toward process and equipment design and evaluation.     

Chronic abdominal pain: role of video-laparoscopic adhesiolysis

Adhesions have been suggested as a possible cause of chronic abdominal pain, but the reports of their etiological role conflict. Lysis of adhesions has been proposed as the therapeutic modality of choice, although the reports of success are controversial. The aim our prospective study was to determine whether laparoscopic adhesiolysis ameliorates chronic abdominal pain in patients with abdominal adhesions. Forty-one patients with chronic abdominal pain lasting for more than 6 months, but with no abnormal findings other than adhesions found at laparoscopy, underwent laparoscopic adhesiolysis. 37 patients (90.2%) were available for follow-up after a median time interval of 18 months (range: 12-41 months). Twenty-two patients (59.4%) were free from abdominal pain and 9 (24.3%) patients reported significant amelioration of their pain. Six (16.2%) patients had no amelioration. In conclusion the laparoscopy is an effective tool for the evaluation of patients with chronic abdominal pain, and laparoscopic adhesiolysis cures of ameliorates chronic abdominal pain in more than 80% of patients.     

Hip impact velocities and body configurations for voluntary falls from standing height

OBJECTIVE: To determine prevalence of various pheno- and genotypes of Serpulina sp in young pigs in relation to diarrhea and feed medication in Swedish pig-rearing herds. DESIGN: Isolation of spirochetes. Phenotypical and genotypical classification. SAMPLE POPULATION: Young pigs (n = 358) in 19 pigrearing herds. PROCEDURE: Serpulina isolates were classified according to a biochemical scheme based on hemolysis, indole production, hippurate hydrolysis, and alpha-galactosidase, alpha-glucosidase, and beta-glucosidase activities. The 16S rRNA sequences for 10 of the field strains and 2 type strains of Serpulina spp were aligned and compared. Minimum inhibitory concentrations of olaquindox for 9 of the strains were determined. RESULTS: Weakly beta-hemolytic intestinal spirochetes (WBHIS) were isolated from 17 of the herds and 65% of the samples. More than 1 phenotype of WBHIS was found in 12 of the 19 herds. S hyodysenteriae was not isolated in any of the herds. Hippurate-positive WBHIS were isolated in 6 of 7 herds affected by diarrhea, but in only 1 of 8 herds without diarrhea. Hippurate-positive strains were closely related to the pathogenic strain P43 if judged from sequence comparisons. Strains with the same biochemical profile isolated within a herd had identical sequences, but when isolated from different herds, sequence differences were observed. The prevalence of WBHIS was reduced in herds medicated with olaquindox. Investigated field strains had minimum inhibitory concentration values < or = 1 microgram/ml for olaquindox. CONCLUSION: The presence of WBHIS, with the ability to hydrolyze hippurate, was related to diarrhea in pig herds. CLINICAL RELEVANCE: Potentially pathogenic WBHIS can be distinguished from nonpathogenic strains by the hippurate hydrolysis test.     

Polymorphism of bacteriophage T7

For viruses made of nucleic acid and protein, the structure of the protein outer shell has, in the past, been found to be uniquely determined by the viral genome. However, here, non-denaturing agarose gel electrophoresis of bacteriophage T7 reveals two states of the mature T7 capsid; the conditions of growth are found to alter the population by T7 of these two electrophoretically defined states. Both states have been previously observed for a genetically altered T7 and they are observed here for wild-type T7. The average electrical surface charge density of a bacteriophage particle (delta) determines its state; the delta of particles in both states is negative. For a given condition of growth, the population of these two states is influenced by the extent to which the major T7 outer shell protein, p10A, is accompanied by its minor readthrough variant, p10B. Comparison of the two electrophoretic states reveals the following. (1) No difference in radius is present in the outer shell (+/-2%). (2) As the pH of electrophoresis is either increased or decreased from neutrality, the state becomes more highly populated for which delta is greater in magnitude (state 1). By changing the pH, some T7 particles are made to change state. (3) Particles in state 1 adsorb less quickly to host cells than do the particles in the alternative state (state 2). This latter observation suggests the hypothesis that state 1 evolved to reduce the probability of re-initiating an infection when conditions are not favorable for growth. This hypothesis is supported by the observation that, as conditions of growth become apparently more unfavorable, progeny increasingly populate state 1.     

Safety of intrauterine contraceptive devices during MR imaging

OBJECTIVE: We report a case of candidiasis of the upper urinary tract that presented as acute renal failure associated with septic syndrome. The patient initially required hemodialysis. Right hydronephrosis and perirenal collection were observed on ultrasound examination. METHODS: A percutaneous nephrostomy was performed. Nephrostomy urine cytology and cultures were positive for Candida tropicalis. An anterograde pyelography showed a 'fungus ball' in the urinary tract. RESULTS: Therapy with oral fluconazole and percutaneous amphotericin B achieved excellent results. CONCLUSIONS: Candidiasic urinary infection of the upper urinary tract often produces obstructive uropathy requiring percutaneous nephrostomy, which can also be used to instill amphotericin B. Combination therapy with amphotericin B and fluconazole can achieve excellent results.     

New advances in the treatment of infertility in women with ovarian failure

Ovarian failure is heterogeneous in etiology and may occur at various points in a woman's life. As such, it may interfere with fertility. Clinical presentation ranges from complete cessation of menses to oligomenorrhea to the continuation of menses with elevated gonadotropins. Various therapies have been used in an attempt to induce fertility, including sex steroids and gonadotropin-releasing hormone agonists to suppress circulating gonadotropin alone or in combination with estrogen or gonadotropin-releasing hormone agonists to induce ovulation. Corticosteroids are also used to overcome autoimmunity. Randomized therapeutic trials are rare and fail to demonstrate any significant improvement in ovulation and pregnancy rates. Donor oocytes have demonstrated high success rates and have proven to be useful in patients with both premature ovarian failure and natural menopause. Pregnancies have been initiated and maintained in women through 60 years of age. Thus, for those accepting of the technique, oocyte donation appears to be the treatment of choice for hypergonadotropic hypogonadism.     

"Cadism": Odd man out.

Comments that L. B. Silverstein's (see record 1992-05293-001) article on child care and maternal employment contributes unfounded and damaging misbeliefs regarding fathers. The dad-as-cad myth suggests intentional malevolence or at least blatant failure by fathers to care for others, and suggests that their failure to share equally in child care and household management is the primary cause of marital conflict. W. B. Johnson and D. Hayes propose a research agenda for fathering that originates in a coherent model of male development in the context of ever-changing environmental demands. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nonlinearity of p-i-n photodetectors

At higher operating frequencies, the field dependence of the carrier velocity in p-i-n photodetectors generates harmonics and intermodulation products that can degrade the dynamic range of RF fiber-optic links. The authors present both a perturbational theory and measured harmonic data for a p-i-n photodiode operated at very high power densities which show that this and other detector nonlinear effects need not seriously compromise link performance. In particular, neither transit-time nor static nonlinearities in p-i-n photodiodes need limit the dynamic range of fiber-optic links operating below 5 GHz. The fact that the theoretical bandwidth of the photodiode, with all parasitic capacitance and inductance ideally removed, is 17 GHz, suggests that comparable spur-free performance should be achievable at X and Ku-band frequencies, once packaging parasitics are reduced