Species differences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile

The carcinogenic effects of acrylonitrile in rats are believedto be mediated by its DNA-reactive epoxide metabolite, 2-cyanoethyleneoxide (CEO). Previous studies have shown that conjugation withglutathione is the major detoxication pathway for both acrylonitrileand CEO. This study investigated the role of epoxide hydrolasein the hydrolysis of CEO by HPLC analysis of the products from[2,3-¹⁴C]CEO. CEO is a relatively stable epoxide with a half-lifeof 99 min at 37°C in sodium phosphate buffer (0.1 M), pH7.3. Incubation with hepatic microsomes or cytosols from maleF-344 rats or B6C3F1 mice did not enhance the rate of hydrolysisof CEO (0.69 nmol/min). Human hepatic microsomes significantlyincreased the rate of hydrolysis of CEO, whereas human hepaticcytosols did not. Human hepatic microsomal hydrolysis activitywas heat-sensitive and potently inhibited by 1,1,1-trichloropropeneoxide (IC₅₀ of 23 µM), indicating that epoxide hydrolasewas the catalyst. The hydrolysis of CEO catalyzed by hepaticmicrosomes from six individuals exhibited normal saturationkinetics with K_M ranging from 0.6 to 3.2 mM and V _max from 8.3to 18.8 nmol hydrolysis products/min/mg protein. Pretreatmentof rodents with phenobarbital or acetone induced hepatic microsomalhydrolysis activity toward CEO, whereas treatment with ß-naphthoflavone,dexamethasone or acrylonitrile itself was without effect. Thesedata show that humans possess an additional detoxication pathwayfor CEO that is not active in rodents (but is inducible). Thepresence of an active epoxide hydrolase hydrolysis activitytoward CEO in humans should be considered in assessments ofcancer risk from acrylonitrile exposure.     

A novel model to study bacterial adherence to the transplanted airway: Inhibition of Burkholderia cepacia adherence to human airway by dextran and xylitol

BACKGROUND: Lung infection with Burkholderia cepacia complex before lung transplantation in patients with cystic fibrosis is a major risk factor for decreased post-operative survival rates compared with those of patients colonized with the more common opportunistic pathogen Pseudomonas aeruginosa. Because adherence to mucosal surfaces is an important initial step in infection, we investigated the use of non-toxic neutral polysaccharides and a sugar alcohol to prevent adherence of B cepacia complex to allograft airway epithelium. METHODS: We used human airway explants prepared from donor tracheobronchial tissue to test the effect of dextrans and xylitol in inhibiting the binding of Burkholderia cepacia complex. We used immunofluorescence and electron microscopy to determine the distribution of bacteria in the explants. RESULTS: Burkholderia cepacia complex bound to the explants and was found only in the surface mucus layer. Dextran 40 kd applied before adding the bacteria decreased the number of bound organisms by 80% to 99%. Smaller molecular mass dextrans (4 and 20 kd) were ineffective. Xylitol inhibited bacterial binding by 67% to 85%. Both agents seemed to decrease the thickness of the surface mucus, suggesting that they may indirectly inhibit bacterial binding by removing adherent surface mucus. CONCLUSIONS: Treating donor lungs with dextran 40 kd or xylitol before (and possibly after) surgery may inhibit the adherence of Burkholderia cepacia complex to airways and may prevent or decrease subsequent infection of the allografts.     

Evaluation of specialized laparoscopic suturing and tying devices.

BACKGROUND: Laparoscopic suturing and tying constitute advanced minimally invasive surgery skills. Developing proficiency in the standard methods with needle drivers is often an arduous process. Recent advances in laparoscopic instrumentations has allowed for easier methods of suturing and tying. This study investigated the hypothesis that the use of a specialized suturing device and a specialized tying device allows inexperienced medical students to suture and tie laparoscopically. METHODS: Preclinical medical students who had not received any training in open or laparoscopic surgery were included in this investigation. Each student was given a 5-minute demonstration of a specialized suturing device and a specialized tying device. The medical students were not allowed to deploy either device before actual use. After the demonstration, each student was given the device to use in a porcine model. Times were recorded and a subjective grade was given for each student. RESULTS: Twenty medical students were involved in this study. All medical students were able to complete the task of suturing and tying. The average time to suture was 104.6 seconds and the average time to tying was 31.2 seconds. The average subjective performance grade was 90 (out of 100). CONCLUSION: Specialized devices are easy to learn and use for laparoscopic suturing and tying with minimal instruction even for inexperienced medical students. Even surgeons who are not well versed in laparoscopic surgery should be able to suture and tie with certain laparoscopic instruments.     

ENDOSCOPY ASSISTED REMOVAL OF FERROMAGNETIC COINS WITH NOVEL MAGNETIC INSTRUMENT

Background: Ingestion of coins is a common clinical problem in children. Many of the coins are ferromagnetic and can be retrieved with the help of a magnet. We describe the use of a novel endoscopic accessory for removing ferromagnetic coins. Material and methods: Two magnet discs of 1.5 cm diameter were joined to a 200 cm steel wire of 0.75 mm thickness with a terminal 5 cm spring. A Teflon tube (160 cm, 7 F) was used along with this instrument as a sleeve. The use of this accessory was analyzed prospectively in subjects presenting with a history of coin ingestion. The time taken for removal of coins, complications during the procedure and failure rate was noted. Effect of the magnet on cardiac rhythm was also noted during the procedure. Results: A total of 55 children (mean age 5.1 ± 2.3 years) with coin ingestion presented over a period of 1 year. Forty‐four coins were ferromagnetic. All ferromagnetic coins were removed successfully. Mean time for removal was 68 ± 22 s. No complications were encountered. Conclusion: The novel magnetic instrument is precise, safe and quick for the removal of ferromagnetic coins under direct vision.     

Domiciliary mechanical ventilation in a patient with severe chronic obstructive lung disease and respiratory failure.

A patient of chronic obstructive pulmonary disease (COPD) with cor-pulmonale and chronic respiratory failure, who was given intermittent positive pressure ventilation at home, is reported. The patient did remarkably well on home mechanical ventilatory support. We believe this to be the first case report of domiciliary mechanical ventilation in a patient of COPD from India.