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.     

Evidence for disturbed S-adenosylmethionine : S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions?

BACKGROUND: Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. METHODS: In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. RESULTS: Folic acid and vitamin B12 in plasma were similar in patients (mean +/- SEM 25+/-2 nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6+/-3.6 micromol/l, 381+/-32nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/-0.4 micromol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. CONCLUSION: Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.     

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training

PURPOSE: To determine the radiologic characteristics of cystic dystrophy of the duodenal wall. MATERIALS AND METHODS: Ten patients with cystic dystrophy of the duodenal wall and chronic pancreatitis underwent ultrasonography (US) (n = 10), computed tomography (CT) (n = 10), endoscopic US (n = 5), and endoscopic retrograde cholangiopancreatography (ERCP) (n = 9). Cystic dystrophy of the duodenal wall was classified as either cystic or solid. The imaging findings were retrospectively analyzed and compared with findings at pancreatoduodenectomy (n = 10). RESULTS: The more frequent cystic type (n = 7) of cystic dystrophy of the duodenal wall was characterized by the presence of easily recognizable cystic lesions (diameter, more than 1 cm), located within the thickened wall of the second portion of the duodenum. The solid type (n = 3) of cystic dystrophy of the duodenal wall demonstrated fibrous thickening of the duodenal wall within which small cysts (diameter, less than 1 cm) were present. The intraduodenal cysts were usually elongated or bilobate with a thick wall. The thickening of the duodenal wall appeared as a solid layer between the duodenal lumen and the pancreas, hypoechoic at US, isoattenuating at unenhanced CT, and hypoattenuating in the early phase (after initiation of infusion of contrast material) and isoattenuating in the late phase (after completion of infusion) at contrast material-enhanced CT. Findings at retrospective analysis of CT and endoscopic US images were characteristic. CONCLUSION: Imaging modalities, notably CT and endoscopic US, helped establish the diagnosis of cystic dystrophy of the duodenal wall.     

Ethnicity and cardiovascular risk: variations in people of African ancestry and South Asian origin

Mortality from coronary heart disease (CHD), stroke and end-stage renal failure are high in South Asian migrants in the UK. This is associated with high prevalence of diabetes and hypertension. These seem to be manifestations of a metabolic syndrome with insulin resistance (hyperinsulinaemia) and central obesity (based on high waist-to-hip ratio rather than on conventional measures of body mass index). This is associated with sedentary lifestyle, high serum triglycerides and low HDL-cholesterol. Mortality from stroke and end-stage renal failure are high in black migrants to the UK (both Caribbeans and West Africans). However, CHD mortality is low in this group. This pattern of mortality is associated with high prevalence of hypertension and diabetes. This group tends to be obese (particularly women) according to conventional measures of body mass index and to have hyperinsulinaemia, low serum triglycerides and high HDL-cholesterol. Conventional risk factors such as cigarette smoking and hypercholesterolaemia are less prevalent in ethnic minority populations in the United Kingdom and unlikely to explain the differences seen between groups, although each risk factor is likely to contribute to the variation in vascular disease within each group. There is difficulty in reconciling the results of migration studies (eg, from rural to urban environments) pointing to major environmental influences on the changes in cardiovascular risk factors with the consistent pattern of disease of ethnic groups across the world and in subsequent generations, suggesting a certain degree of genetic susceptibility. Important environment-gene interplays might be underlying some of these processes. The detection and management of hypertension and diabetes are still unsatisfactory in inner city areas and show variations by ethnic origin. Strategies for the control of CHD and stroke adopted in European countries directed mostly to white populations may be inappropriate for ethnic minority populations.     

Voluntarism: is it a useful concept for health education in the accident and emergency department?

As the year 2000 looms closer, the emphasis on health education as a means of attaining the 38 targets for 'Health for All' increases. Despite various initiatives, little, if any, progress has been made in narrowing the health divide. Currently, terms such as 'self-care', 'individual responsibility' and 'community empowerment' are often used with emphasis on individual freedom to choose. The author contends that to assume all individuals have that freedom and act voluntarily, is to deny the impact of social structure on health. Health education and the concept of voluntarism will be critically examined from the perspective of nursing in an accident and emergency department.     

Laparoscopic cholecystectomy and gallbladder cancer: a diagnostic and therapeutic dilemma

The correct treatment strategy of patients with unsuspected gallbladder cancer undergoing laparoscopy, and the prevention of delayed diagnosis are current issues. We report a case of late diagnosis with umbilical metastasis and poor survival. A policy of careful inspection of the gallbladder and a cautious strategy in the case of gross alteration of its external morphology seems advisable during laparoscopic cholecystectomy. Although no agreement exists concerning the best treatment in the event of delayed diagnosis, the adopted strategy is contingent on patient status, disease stage and the possibility of performing appropriate follow-up.     

PKI dies hard

Public Key Infrastructure is staging a comeback, according to new research from European IT user association EEMA.     

Conserved features of TBE1 transposons in ciliated protozoa

BACKGROUND: Accessory function (AF) is one way antigen presenting cells generate sufficient secondary signals for optimal T-cell proliferation and IL-2 production. In general, alveolar macrophages (AM) are inferior accessory cells in comparison to monocytes whereas in sarcoidosis AF of AM is increased. METHODS: We compared the accessory index (AI) of AM and peripheral blood monocytes (PBM) of 41 patients with inactive sarcoidosis (SAR I, n = 12); active sarcoidosis with new or progressing symptoms (SAR II, n = 19), active sarcoidosis with spontaneous remission (SAR III, n = 10), tuberculosis (TB, n = 12), hypersensitivity pneumonitis (HP, n = 12), Wegener's disease (WD, n = 2), undefined alveolitis (UA, n = 8) and chronic obstructive pulmonary disease (COPD, n = 6) by employing the histoincompatibility-insensitive Jurkat cells as indicator cells. RESULTS: Compared with the controls (1.08 +/- 0.3) AMs of all groups but SAR I (AI: 0.96 +/- 0.42) exhibited significantly increased AIs (SAR II: 3.6 +/- 3.9; SAR III: 3.2 +/- 2.4; TB: 2.8 +/- 2.2; HP: 3 +/- 2; UA: 2.7 +/- 2.3; COPD: 3.1 +/- 2.2; p < 0.05 for all comparisons). Only in HP, AI of PBM was significantly increased compared with controls (3 +/- 1.5, 1.3 +/- 0.5, respectively; p < 0.001). Alveolar macrophages from patients with arcoidosis, TB, and HB express the costimulatory molecule CD80 on their surface and anti-CD80 antibodies inhibited the IL-2 release of Jurkat cells in this system to 59 +/- 27%. CONCLUSIONS: Our data demonstrate that AM from patients with various diseases have the capability to act as competent accessory cells and that the reported accessory function of these cells is at least in part mediated by the expression of CD80.     

Cosleeping (bedsharing) among infants and toddlers

This study was designed to investigate the effect of retaining coronal tooth substance on the performance of post-retained core materials, and to compare the fracture resistance of the system with an intact tooth prepared to similar dimensions. Ten teeth restored with post-retained silver amalgam, and 10 teeth restored with silver-glass cermet, all with a retained single wall of coronal tooth substance, were compared with 10 unrestored teeth prepared to similar dimensions when subjected to a shearing load. The results showed no statistically significant difference between the unrestored teeth and those restored with a silver-glass cermet. Whilst the teeth restored with silver amalgam had a significantly higher fracture resistance (P > 0.01) there was greater tendency to root fracture.