Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Consequences of foot binding among older women in Beijing, China.

OBJECTIVES: This study examined the prevalence and consequences of foot binding in older Chinese women. METHODS: Women older than 70 years in Beijing, China, were assessed for bound feet, falls, functional status, and bone density. RESULTS: Thirty-eight percent of women aged 80 years and older and 18% of women aged 70 through 79 years had bound-foot deformities. Women with bound feet were more likely to fall, less able to squat, and less able to stand up from a chair without assistance than women with normal feet. They also had 14.3% less functional reach (a test of balance) and 5.1% lower hip bone density. CONCLUSIONS: Foot binding has caused substantial disability that is still evident in many elderly Chinese women.     

Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine.

OBJECTIVE: To assess the use of infiltration with local anaesthetics levobupivacaine and bupivacaine, during inguinal hernia repair. DESIGN: Double-blind, randomised study. SETTING: Postgraduate medical school, United Kingdom. SUBJECTS: 69 male patients aged 18 years or older. INTERVENTIONS: Wound infiltration with 0.25% levobupivacaine and 0.25% racemic bupivacaine. MAIN OUTCOME MEASURES: Area under the curve (AUC) of visual analogue scale (VAS) scores for postoperative pain at rest in the supine position, rising from the supine to the sitting position, and walking, against time for both treatment groups. RESULTS: There were no significant differences between treatment groups for the AUC of VAS scores for postoperative pain, global verbal pain rating or time to first dose of analgesic medication. CONCLUSIONS: Levobupivacaine exerts a similar anaesthetic and analgesic effect to racemic bupivacaine when infiltrated both intraoperatively and during the early postoperative period for elective inguinal hernia repair.