Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.     

Assessment of the Severity of Asthma in a Family Practice

The objective of this study was to evaluate clinical history and self-perception of severity as predictors of asthma severity. A short-term longitudinal study was conducted in a family practice in Melbourne, Australia, utilizing peak flow monitoring, medication diary, and self-administered asthma severity questionnaire. Seventy-two asthmatic subjects with a positive bronchodilator or exercise test, aged between 6 and 79 years, were studied. Symptom and treatment items were correlated with peak flow variability and minimal peak expiratory flow rate (PEFR). An asthma severity scale was generated using the partial credit version of Item Response Theory and the participants' severity scores were validated against lung function tests and medication usage. Quantitative modeling procedures were used to investigate the interrelationships of factors associated with peak flow variability. Severity scores demonstrated significant relationships with peak flow variability (partial r = 0.34) and treatment items. Self-perceived severity of asthma in the preceding 2 weeks showed significant association with peak flow variability (partial rho = 0.46) and minimal PEFR (rho = -0.41). The severity module of the Monash Respiratory Questionnaire is a valid and reliable instrument. The most important symptoms appear to be the frequency of use of bronchodilator and frequency of nocturnal attacks. A carefully structured clinical history in conjunction with the peak flow criteria of variability and minimal peak flow rate would be appropriate in the evaluation of asthma severity. Patients' self-perception of the severity of their asthma needs further evaluation.     

High Carboxyhemoglobin Concentrations Occur in Swine during Desflurane Anesthesia in the Presence of Partially Dried Carbon Dioxide Absorbents

Background: Increased carboxyhemoglobin concentrations in patients receiving inhalation anesthetics (desflurane, enflurane, and isoflurane) have been reported. Recent in vitro studies suggest that dry carbon dioxide absorbents may allow the production of carbon monoxide.

Methods: The authors used high fresh oxygen flow (5 or 10 l/min) through a conventional circle breathing system of an anesthesia machine for 24 or 48 h to produce absorbent drying. Initial studies used 10 l/min oxygen flow with the reservoir bag removed or with the reservoir bag left in place during absorbent drying (this increases resistance to gas flow through the canister). A third investigation evaluated a lower flow rate (5 l/min) for absorbent drying. Water content of the absorbent and temperature were measured. Pigs received a 1.0 (human) minimum alveolar concentration desflurane anesthetic (7.5%) for 240 min using a 1 l/min oxygen flow rate with dried absorbent. Carbon monoxide concentrations in the circuit and carboxyhemoglobin concentrations in the pigs were measured.

Results: Pigs anesthetized with desflurane using Baralyme exposed to 48 h of 10 l/min oxygen flow (reservoir bag removed) had extremely high carboxyhemoglobin concentrations (more than 80%). Circuit carbon monoxide concentrations during desflurane anesthesia using absorbents exposed to 10 l/min oxygen flow (reservoir bag, 24 h) reached peak values of 8,800 to 13,600 ppm, depending on the absorbent used. Carboxyhemoglobin concentrations reached peak values of 73% (Baralyme) and 53% (soda lime). The water content of Baralyme decreased from 12.1 +/- 0.3% (mean +/- SEM) to as low as 1.9 +/- 0.4% at the bottom of the lower canister (oxygen flow direction during drying was from bottom to top). Absorbent temperatures in the bottom canister increased to temperatures as high as 50 [degree sign] Celsius. With the reservoir bag in place during drying (10 l/min oxygen flow), water removal from Baralyme was insufficient to produce carbon monoxide (lowest water content = 5.5%). Use of 5 l/min oxygen flow (reservoir bag removed) for 24 h did not reduce water content sufficiently to produce carbon dioxide with desflurane.     

Cloning and characterisation of the adenosyl phosphosulphate kinase gene from Aspergillus nidulans

The sD gene of Aspergillus nidulans has been cloned by heterologous screening of rationally selected cosmids. Co-transformation of the sD50 mutant JMP1 confirmed the presence of a functional gene. Sequence analysis determined this gene to be 680 bp in length, containing a 59-bp intron and encoding a protein of 206 amino acids. A protein-sequence comparison revealed a similarity to the C-terminal region of ATP sulphurylase, the sC gene product. Further sequence comparison revealed differences in a consensus sequence ATP-binding motif, indicating non-functionality of the APS kinase-like domain of ATP sulphurylase, and confirms sD as the gene encoding APS kinase in A. nidulans. Received: 17 April / 29 August 1997