Hypothermia protects brain function in acute carbon monoxide poisoning

The role of body temperature in the morbidity and mortality resulting from acute severe carbon monoxide (CO) poisoning (2400 ppm CO, 90 min) was investigated using an unanesthetized animal model. Modified Levine prepared female rats (left common carotid artery and jugular cannulated) displayed a lower rate of recovery period (4 hr) re-warming, and an increased mortality rate and behaviorally-assessed neurologic index (NI) compared to normal rats. This indicated their greater susceptibility to CO hypoxia, although the degree of CO-induced hypothermia was the same in both groups. The whole-body cooling of Levine rats to a similar extent prior to CO exposure increased somewhat the post-CO re-warming rate, and marginally decreased NI and mortality during CO exposure (in-CO). In contrast, maintenance of constant body temperature by external heating during CO exposure resulted in a negative post-CO re-warming rate and sharply increased NI and in-CO mortality. Normal euthermic rats were much less severely affected by CO. The results suggest that hypothermia, whether CO-induced or produced by prior cooling, provides measurable protection of brain function during acute severe CO poisoning, and that maintenance of body temperature increases in-CO mortality and interferes with ability to thermoregulate and increases NI in survivors.     

A study on the metabolism of galactose cataract using a 31P-NMR spectroscopy

Using a 31P-NMR spectroscopy, we monitored the metabolic kinetics of energy organophosphate compound in rat lens during the process of generating galactose cataract. The most remarkable metabolic change in the earlier phase of galactose cataract formation was found in alpha-glycerophosphate. This increased significantly, as compared to controls, since the day 3 of giving feed containing 25% galactose. The high level lasted for up to three weeks, decrease followed by a gradual decrease and subsequently a significant decrease at five weeks. Adenosine triphosphate (ATP) showed a significant decrease in the galactose group compared to the controls from two weeks after beginning of the experiment and the decrease continued. Inorganic orthophosphate increased gradually in the galactose group as compared to the controls, the increase being of significance at one week reading a maximum at two weeks followed by a subsegment decrease. Our basic study suggests that 31P-NMR spectroscopy is a useful technique in lens of the metabolic kinetics, to noninvasively determine the pathophysiology of galactose cataract, which has been studied biochemically and histologically.     

Enantiomeric interaction of flurbiprofen in the rat

Flurbiprofen [FL, (+/-)-2-(2-fluoro-4-biphenylyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which is commercially available as a racemate. The anti-inflammatory activity of FL, however, appears to be mainly due to the S enantiomer. Recently, it has been postulated that, in both humans and rats, the two enantiomers of FL may interact when racemic doses are given. This study examines the above postulate in the rat by administration of single iv doses of racemic FL (10 mg/kg), and R- and S-FL (5 mg/kg of each). Plasma concentrations (0-12 h) of the enantiomers were measured using a stereospecific HPLC assay. A significant interaction was noticed between the enantiomers: mean AUC +/- SD of R-FL was reduced from 115.3 +/- 21.3 to 49.0 +/- 10.4 mg/L.h as a result of S-FL coadministration. A trend towards reduced S-FL plasma concentration was also evident when the enantiomer was given as the racemate [mean AUC +/- SD; 176.8 +/- 37.7 racemate versus 241.4 +/- 86.2 mg/L.h alone]. The reduction in S-FL, however, was not significant due perhaps to the observed interanimal variation. While the enantiomeric interaction caused a significant enlargement of the volume of distribution of R-FL, it failed to alter the terminal half-life of the enantiomer. It is suggested that the interaction is a result of displacement from plasma protein binding sites of one enantiomer by the other.     

Viral hepatitis in the US Navy, 1975-1984

The epidemiology of viral hepatitis in US Navy enlisted personnel was reviewed for the years 1975-1984. Hospital discharge summaries of all active duty enlisted personnel admitted to a US Navy treatment facility were used for the study. From 1975 to 1984, total first hospitalizations for viral hepatitis declined from 128 per 100,000 personnel (95% confidence interval (Cl) 118-139) to 56 per 100,000 personnel (95% Cl 50-63). The highest incidence of acute viral hepatitis (115 per 100,000 personnel) was found in the youngest age groups aged 24 years and less. Risk factors for acute hepatitis included a previous hospitalization with either drug abuse (relative risk = 363) or a sexually transmitted disease (relative risk = 25) listed among the discharge diagnoses. Having a medical job classification was also associated with an increased risk of acute hepatitis. The steep decline in the incidence of viral hepatitis during this 10-year period may have been due to decreasing drug abuse in the US Navy. Immunization of high-risk groups in the US Navy with hepatitis B vaccine could be an effective policy for the prevention of acute viral hepatitis.     

Hearing loss and otitis media on Guam: impact of professional services

In less than two decades, there has been a dramatic reduction in the prevalence of otitis media and perforations among Guam's school-aged children. In addition, hearing loss due to chronic middle ear disease as a cause of disqualification from military service has dropped from a first rank order cause to next-to-last. However, there has been no reduction in the prevalence of otitis media in the preschool population. The reduction in chronic ear disease is the result of improved access to primary care, intensive hearing screening, wide availability of audiologic diagnostic and follow-up services, and comprehensive otologic care. It is essential that these services continue to be available to Guam's children to avoid a reversal of these dramatic gains. Attention must now focus on how to achieve similar gains for Micronesian children who remain restricted in their access to these resources.     

Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guinea pig ileum and in intact mice. They were found to be moderately potent muscarinic antagonists or weak partial agonists. The new compounds were less potent than 2 in inhibiting (-)-[3H]-N-methylscopolamine binding in the rate cerebral cortex. Thus, structural modifications of 2 in which part of the amide moiety has been connected with the methyl group in the butynyl chain to form a five-membered ring decrease affinity and in most cases abolish efficacy.     

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384) on learning and memory were studied using four different experimental rat models. In electroconvulsive shock- or scopolamine-induced amnesia in the step-through passive avoidance task, DM-9384 improved both types of amnesia when administered before the training trial. Aniracetam also showed similar but somewhat weaker effects. Furthermore, in the scopolamine amnesia model, an improvement was confirmed with arecoline. The dose-response curves for these compounds were bell-shaped. In the shuttle box active avoidance task, DM-9384 administered daily 1 hr before each training session facilitated the acquisition process of the avoidance response. In addition, the experiment of light-dark discrimination task with positive reinforcement showed that this compound administered daily after each session slightly accelerated the acquisition process of the correct response. These results suggest an ability of DM-9384 to enhance cognitive functions.