Decreased Extractability of DNA from Proteins in the Rat Nasal Mucosa after Acetaldehyde Exposure

Decreased Extractability of DNA from Proteins in the Rat NasalMucosa after Acetaldehyde Exposure. LAM, C.-W., CASANOVA, M.,AND HECK, H. D'A. (1986). Fundam. Appl. Toxicol. 6, 541–550.Acetaldehyde and formaldehyde have been found to induce nasalcancer in two species of rodents. To understand the mechanismof carcinogenesis by acetaldehyde, studies were carried Outto determine whether acetaldehyde can react with DNA in targettissues of the rat nasal cavity. When fresh homogenates of thenasal respiratory mucosa were incubated with acetaldehyde (distilledunder N at concentrations of 10, 100, or 500 mM, followed bysolubilization and extraction with a strongly denaturing aqueous-immiscibleorganic solvent mixture, a decrease was observed in the amountof DNA partitioned into the aqueous phase at the two higheracetaldehyde con centrations. The absent DNA was recovered fromthe interfacial layer by proteolytic digestion. Similarly, incubationof calf thymus nucleohistones with acetaldehyde (100, 300, or1000 mM) or with formaldehyde (10, 30, or 100 mM) followed byprecipitation of the DNA with H₂SO₄ and analysis of the supematantsby sodium dodecyl sulfate-polyacrylamide gel electrophoresisresulted in concentration-dependent decreases in the quantitiesof histone proteins released from the DNA. These results indicatethat acetaldehyde as well as formaldehyde can form DNA-proteincrosslinks in vitro. A single 6-hr exposure of male Fischer-344rats to acetaldehyde (100, 300, 1000, or 3000 ppm) resultedin a significant increase relative to air-exposed controls inthe percent interfacial DNA from the nasal respiratory mucosaat concentrations equal to or greater than 1000 ppm. No increasein the interfacial DNA from the olfactory mucosa was detectedafter a single 6-hr exposure (1000 or 3000 ppm), but a significantincrease was found in rats exposed repeatedly (6 hr/day for5 days) to acetaldehyde (1000 ppm). Thus, evidence has beenobtained for the formation of DNA-protein crosslinks by acetaldehydein target tissues of the rat nasal cavity at concentrationssimilar to those that induced nasal cancer.     

Bromocriptine and cocaine cue reactivity in cocaine-dependent patients

Based on previous reports that bromocriptine, a postsynaptic dopamine agonist, reduced cocaine craving and prevented relapse in cocaine-dependent subjects, effects of the drug were evaluated in 20 cocaine-dependent males in an inpatient drug rehabilitation programme. The subjective and physiologic effects of exposure to both cocaine-associated and neutral stimuli, presented using videotapes, were measured at one-week intervals. Between laboratory sessions subjects received either bromocriptine (1.25 mg bid) or a matched placebo, administered in double-blind fashion. Compared with the neutral videotape, the cocaine videotape elicited both a greater desire to use cocaine and more symptoms associated with cocaine self-administration. These results support an appetitive conditioning model of cocaine effects. Bromocriptine, however, had no effect on the cocaine-cue-associated reactivity, which declined over the 1-week interval in both treatment groups. Methodological differences among studies that have examined the effects of bromocnptine in cocaine-dependent subjects may explain the variable findings observed.     

Alcohol and drug abuse treatment at the University of Connecticut Health Center

This article describes a multidisciplinary team approach to the treatment of alcohol and drug dependence and comorbid disorders. The principal aim of this approach is the identification and treatment of patients' chemical dependence, as well as the medical and psychiatric disorders that contribute to and/or stem from the chronic use of alcohol and drugs. The focus of treatment is on the identification of high risk and other problem situations, training coping skills to handle these situations, developing insight, and enhancing patients' motivation for sobriety and ongoing treatment. In this article we describe the features of our program that address these various goals.     

Colonic retinoblastoma protein and proliferation in cancer and non-cancer patients#

Both suppressor oncogene and proliferative activity are believed to indicate colon cancer risk. The retinoblastoma (Rb) gene is a suppressor oncogene affecting cell differentiation. Retinoblastoma gene inactivation is associated with tumour development. However, the relation of the Rb protein to cell proliferation and colon tumour formation is unknown. Retinoblastoma protein quantity was correlated with proliferative activity in flat, unaffected mucosa specimens from 36 cancer patients, 21 non-cancer control subjects and in 29 tumour tissue samples from cancer patients. Nuclear Rb protein was measured by using automated CAS-200 image analysis of monoclonal antibody labelled frozen sections from fresh, surgically removed tissue. All colon cells within 15 whole crypts were imaged. Proliferative activity was also measured by using image analysis with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated directly with proliferative activity in flat mucosa of non-cancer control subjects ( r = 0.63; P < 0.001; n = 21). A significant correlation was also found in flat mucosa specimens of non-metastatic (Duke's stages A and B) cancer patients ( r =0.52; P < 0.01; n = 22). However, Rb protein did not correlate with proliferation in flat mucosa from metastatic (Duke's stages C and D) cancer patients ( r =0.03; NS; n =14) or in cancer tissue ( r =0.068; NS; n =29). Mucosal Rb protein in the colon normally increases as proliferation increases. Dissociation between Rb protein and colon proliferation may occur in flat mucosa in patients with a higher risk of metastatic tumour growth. Future studies comparing Rb protein quantity and proliferative activity may help identify high-risk colon cancer patients.     

integrated health and education input in the development of educational resources about asthma for schools

The development of educational packages on health-related topics has become common in school curricula. This paper describes an integrated health and education input in the development of an educational package about asthma for Year 8 high school students. Ownership and educational relevance of the package (ensuring its appropriateness for inclusion within the Personal Development/Health/Physical Education curriculum) was achieved by collaboration between teachers with an understanding of the principles of curriculum design and health professionals with content knowledge about asthma. The model used for the production of the package about asthma could be extended to other health topics.     

Steroid-Eluting Epicardial Pacing Electrodes: Six Year Experience of Pacing Thresholds in a Growing Pediatric Population

Indications for pacemaker implantation in the pediatric population often include sinus or atrioventricular node dysfunction following surgery for congenital heart defects. However, patient size, cardiac defects, and vascular and valvular concerns may limit transvenous lead utilization. Since the epicardial surface of these patients often exhibits variable degrees of fibrosis from scar tissue formation or pericardial adhesions, chronic low output (2.5/1.6 V, 0.3 ms) epicardial pacing from implant is not currently recommended in children due to frequent threshold changes and electrode exit block. As a result, pacing in children is often viewed as a less efficient system than in adults. The addition of steroid combined with newer low threshold electrode designs however stabilizes the electrode-tissue interface and eliminates postimplant changes seen with standard smooth surface electrodes potentially permitting efficient chronic pacemaker application to all patient ages. The stability of chronic low output epicardial pacing with steroid-eluting electrodes was prospectively studied in 22 patients (ages 2 days-18.5 years, median 3.5 years) for up to 6 years. Chronic pulse width thresholds were compared according to implant site and association of prior cardiac surgery. A total of 26 pacing leads were implanted. The acute implant mean pulse width threshold (2.5 V) for all the electrodes studied was 0.10 ms ± 0.05 ms. Stable low thresholds were maintained for up to 6 years without significant variation from implant. Mean ventricular pulse width thresholds (0.12 ms ± 0.05 ms) were significantly higher (P < 0.001) than atrial thresholds (0.06 ms ± 0.03 ms) at implant and throughout the study period. The thresholds in the patients following cardiac surgery were comparable to those without previous cardiac surgery (P = NS). Stable low thresholds may be chronically maintatined for up to 6 years for epicardial steroid-eluting electrodes irrespective of pacing site or associated cardiac surgery.