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Ethanol-induced reduction of neurotrophin secretion in neonatal rat cerebellar granule cells is mitigated by vitamin E.

Ethanol exposure during nervous system development produces a range of abnormalities, and in humans may lead to the fetal alcohol syndrome. Among the mechanisms hypothesized to play roles in ethanol neurotoxicity are altered expression of supportive neurotrophic factors (NTFs), and cellular disturbances in oxidative processes. In this study, ethanol effects on secretion of two NTFs, brain-derived neurotrophic factor, and neurotrophin-3 were analyzed in neonatal rat cerebellar granule cells, and the potential of the antioxidant vitamin E to modulate ethanol effects was investigated. Ethanol exposure in these preparations reduced NTF secretion, but vitamin E appreciably ameliorated the ethanol effects. Possible mechanisms underlying both the ethanol effects on NTF secretion, and the protection of this antioxidant are considered.

Analysis of Variance↗

Nutritional value for swine of soybean meal produced by isopropyl alcohol extraction.

Three experiments were conducted to compare the nutritional value of soybean meal produced by extraction with 95% isopropyl alcohol (IPA) or hexane (HEX) for swine. The same batch of soybeans and the same processing equipment were used to produce both soybean meals. Analyzed contents of the IPA and HEX meals were, respectively: CP, 48.7, 47.0%; lysine, 3.11, 3.06%; urease, .24, .13 delta pH. In Exp. 1, two soybean meals and dietary lysine at .90 or 1.25% were used in a 2 x 2 factorial arrangement of treatments. Corn-based diets were fed to 32-d-old pigs for 26 d. There were no dietary lysine x soybean meal interactions (P > or = .35). Increasing dietary lysine increased (P < .001) ADG and gain/ feed, but soybean meal source did not affect performance. In Exp. 2, the nutritional value of HEX and IPA meals were evaluated in a N balance study using 34-kg barrows and isonitrogenous corn-based diets containing equal N from either HEX or IPA. Apparent total tract N and DM digestibility were similar for both diets. Nitrogen retention (14.4 vs 13.7 g/d, P < .10) and apparent biological value (56.5 vs 54.5%, P < .05) were slightly higher for HEX than for IPA. The effect of feeding HEX and IPA meals on morphological changes of small intestine in pigs weaned at 21 d of age was investigated in the last experiment. At 28 d of age, weaned pigs that were fed diets containing either HEX or IPA and unweaned control pigs were killed for the examination. Villus height and lamina propria depth at the duodenum were similar among all treatments. At the jejunum, weaned pigs had smaller (P < .05) villus height and greater lamina propria depths (P < .001) than unweaned pigs. Dietary soybean meal source did not affect villus height, but lamina propria depth was less (P < .10) for pigs fed IPA. The results of these experiments indicate that soybean meals produced using IPA or HEX as the solvent have equal nutritional value for swine.

1-Propanol↗

NMR studies of [1-2H]glucose metabolism in Zymomonas mobilis.

In complementary experiments the metabolism of [1-2H]glucose in H2O and of unlabelled glucose in 2H2O by Zymomonas mobilis was examined. The utilization of [1-2H]glucose by Z. mobilis was monitored by high-resolution 2H NMR. The deuterium-labelling pattern and stereochemistry of the ethanols produced from the metabolism of [1-2H]glucose and unlabelled glucose in 2H2O were determined by a combination of 13C and 1H NMR and selective enzyme action. The labelling patterns were explained in terms of enzyme mechanisms and stereospecificity, and metabolite enolization.

Alcohol Dehydrogenase↗

Differences in stroke between white, Hispanic, and Native American patients: the Barrow Neurological Institute stroke database.

BACKGROUND AND PURPOSE: Identification of specific features of stroke in minority populations should lead to more effectively focused treatment and prevention. METHODS: We examined 1290 white (WHI), 242 Hispanic (HIS), 83 Native American (NA), and 101 other stroke and transient ischemic attack (TIA) patients hospitalized at the Barrow Neurological Institute from 1990 through 1996. RESULTS: Chi-square analysis detected significant (P<.05) differences as follows: (1) Stroke types--lacunes more prevalent in NA than WHI and HIS (30% versus 16% and 15%); cardioembolic more prevalent in WHI than HIS (16% versus 9%, NA 14%); hemorrhages more prevalent in HIS than WHI and NA (48% versus 37% and 27%); (2) Risk factors--hypertension more prevalent in HIS than WHI (72% versus 66%; NA 71%); diabetes more prevalent in NA than HIS and WHI (62% versus 36% and 17%); cigarette smoking more prevalent in WHI than HIS and NA (61% versus 46% and 41%); cardiac disease more prevalent in WHI than HIS (34% versus 24%; NA 27%); heavier alcohol intake in NA than HIS than WHI (43% versus 24% versus 17%). There were no significant outcome differences between races for any stroke type. ANOVA detected significantly lower mean age at stroke onset in NA than HIS than WHI (56 versus 61 versus 69 years). CONCLUSIONS: There are significant differences in prevalence of risk factors and stroke types between WHI, HIS, and NA in our hospital-based population. Although the three races appear to respond to risk factors similarly, Hispanics may be especially susceptible to hemorrhage. Further evaluation of these observations in community-based studies will be important.

Age of Onset↗

Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: Effects of neonatal exposure.

The detrimental effects of ethanol exposure during nervous system development have been well established. The cellular mechanisms of ethanol neurotoxicity, however, have not been clearly defined. Recent studies suggest that neurotrophin signaling pathways may be involved in ethanol-mediated neuronal death. The present investigation, therefore, was designed to examine ethanol-induced alterations in neurotrophin receptor protein levels in the developing central nervous system (CNS) following chronic ethanol treatment administered during the early neonatal period. For this study, rats were exposed to ethanol via vapor inhalation from postnatal day 4 (P4) to P10. Brains were then dissected on P10 or P21, and Western blots used to quantify expression of neurotrophin receptors TrkA, TrkB, TrkC, and p75. This early postnatal ethanol treatment produced significant alterations in receptor levels in hippocampus, septum, cerebral cortex, and cerebellum. The alterations seen were variable, with decreases generally found in hippocampus and cerebellum, increases noted in septum, and changes in both directions occurring in cortex. These alterations were generally more prevalent in males than in females. While most of the receptor changes observed were transient, sustained or delayed alterations were occasionally seen in hippocampus, cortex, and cerebellum. These results suggest that developmental ethanol exposure modulates expression of these neurotrophin receptors throughout the CNS, alterations which could have wide-ranging effects on functional CNS development. The possible linkage between such changes and abnormalities encountered in the fetal alcohol syndrome are considered.

Animals↗

Impact of banning alcohol on outpatient visits in Barrow, Alaska.

CONTEXT: Community availability of alcohol affects alcohol consumption patterns and alcohol-related health and social problems. In Barrow, Alaska, an isolated community at the northernmost reaches of the United States, during a 33-month period, possession and importation of alcohol were legal, completely banned, made legal again, and then banned again. OBJECTIVE: To determine the impact of these public policy changes on alcohol-related outpatient visits at the area hospital. DESIGN: Retrospective review of outpatient records; time-series analysis of alcohol-related visits with respect to community alcohol policy. MAIN OUTCOME MEASURES: Total monthly outpatient visits for alcohol-related problems. RESULTS: There was a substantial decrease in the number of alcohol-related outpatient visits when the ban on possession and importation was imposed compared with baseline. When the ban was lifted, outpatient visits increased; when the ban was reimposed, the number of outpatient visits again decreased. Interrupted time-series analyses confirm that the alcohol ban, its lifting, and its reimposition had a statistically significant and negative effect on the number of alcohol-related outpatient visits (P<.05). CONCLUSION: In a geographically isolated community, the prohibition of alcohol can be an effective public health intervention, reducing the health problems associated with alcohol use.

Alaska↗

An objective procedure for quantitating eye irritation based upon changes of corneal thickness.

For four decades, the Draize test has remained the accepted method for evaluating eye irritation. Criticisms center around the inhumane treatment of animals and the irreproducibility of the subjective scoring procedure. The objective of this study was to determine if changes in corneal thickness obtained using a slit-lamp pachometer could be used to replace the Draize scoring procedure and provide a method for quantifying ocular irritation. Twenty-four chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics) were instilled in the conjunctival sacs of rabbits and irritation monitored by Draize scoring and changes in corneal thickness. The Draize procedure was more adept at detecting minor conjunctival damage, but corneal thickness exhibited less variation and increased sensitivity for detection of healing reactions. A significant linear correlation (y = 1.736 chi + 92.883) was established between Draize score and corneal thickness changes with a correlation coefficient (r) of 0.86 and an F-value for regression of 261.3. Using these findings, an ocular irritation ranking system is proposed based upon the percentage of corneal swelling. Ocular irritation potential was ranked for the chemical groups tested (surfactants greater than alcohols greater than ketones or acetates greater than aromatics). Quantitation of ocular irritation from changes in corneal thickness provides objective, numerical data applicable to standard parametric statistical procedures. This should eliminate the subjective bias inherent to Draize scoring and decrease intra-and interlaboratory variability.

Acetates↗

A critical evaluation of predicting ocular irritancy potential from an in vitro cytotoxicity assay.

Numerous in vitro cytotoxicity assays have been proposed as potential alternatives to the Draize eye irritancy test. The results reported, based upon the rank correlation of ocular irritancy with cytotoxicity, have been encouraging. However, direct calibration of in vivo to in vitro data utilizing several categories of chemicals has not been reported. This study evaluated the use of in vitro cytotoxicity data for predicting the ocular irritancy potential of 24 chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics). BALB/c 3T3 cells were grown overnight, then exposed for 30 min to at least four different concentrations of each chemical (expressed as volume percentage). Linear regression analysis of the log concentration versus percentage of control growth was used to calculate the concentration of toxicant that inhibited the normal growth rate by 50% (GI50). The rank ordering of cytotoxicity based upon the GI50s was surfactants greater than aromatics greater than alcohols greater than ketones or acetates. The larger molecular weight representative of each series (i.e., 2-ethyl-1-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances. The GI50 values were then directly calibrated against in vivo ocular irritancy quantitated as percentage corneal swelling following exposure of rabbits to the same test chemicals. A significant linear correlation between cytotoxicity and ocular irritancy was established only for surfactants and alcohols. For acetates, ketones, and aromatics there was little correlation. The overall poor correlation between cytotoxicity and ocular irritancy was attributed to differences in mechanisms of irritancy. The lack of correlation illustrates that in vitro cytotoxicity data cannot be used to predict the ocular irritancy potential of a broad spectrum of chemicals.

Acetates↗

Methylmercury and the health of autochthons in northwest Quebec.

We conducted a cross-sectional epidemiologic and clinical study to evaluate the nature, magnitude, and frequency of unfavourable health states among residents of northwest Quebec. Of particular interest were the possible occurrence of Minamata disease and any other neurological abnormalities. We also sought to determine whether industrial or naturally-occurring mercury in the region's environment were causally associated with any disorders that might be detected. A total of 321 subjects were studied in four groups with contrasting exposure to point-source mercury from a chlor-alkali plant in the area. Methylmercury in hair served as the marker of subject's ingestion of any organic mercury (natural or industrial). Ten pre-chosen target variables, seven clinical and three neurophysiological, were assessed in all subjects. Relationships between mercury in hair and each target variable were calculated. We determined whether gradients in target variables corresponded to gradients in potential exposure of the subjects to the aquatic emissions of the chlor-alkali plant. Minamata disease was not found. Diabetes and alcohol-related health problems assessed as important clinically plausible confounders, were common. Differences in frequency or magnitude of clinical, toxicological, and physiological findings among the contrast groups were small and not of clinical or statistical significance. There were definite relationships between mercury in hair and four target variables despite the low values of mercury measured and the mild nature of the health problems observed. This would suggest that verifiable biological threshold levels for clinical effects, if such exist, may be substantially lower among Canadians than those currently adopted as policy for adults elsewhere. A gradient was found only for two of the ten target variables. Clinically meaningful alternate hypotheses for observed health effects emerge in the data and agree with observations in the field made by consulting clinical experts.

Animals↗

Total radioactive residues and clenbuterol residues in swine after dietary administration of [14C]clenbuterol for seven days and preslaughter withdrawal periods of zero, three, or seven days.

Nine barrows (23.8 +/- 0.9 kg) and 9 gilts (23.1 +/- 0.9 kg) were used to determine the disposition of radiocarbon after oral [14C]clenbuterol (4-amino-alpha-[t-butylaminomethyl]-3,5-dichlorobenzyl [7-(14)C]alcohol hydrochloride) administration and to determine total and parent residues in edible tissues. Three barrows and three gilts, housed in metabolism crates, were fed 1 ppm [14C]clenbuterol HCl for seven consecutive days in three separate trials; a single barrow and gilt from each trial was slaughtered after 0-, 3-, or 7-d preslaughter withdrawal periods. Urine and feces were collected during the dosing and the withdrawal period; edible and inedible tissues were collected at slaughter. Total recovery of radiocarbon was 94.2 +/- 6.5%. Total clenbuterol absorption was greater than 75% for barrows and 60% for gilts. Total radioactive residues in tissues were not different (P > 0.05) between barrows and gilts. Concentrations of parent clenbuterol in liver, kidney, skeletal muscle, adipose tissue, and lung did not differ between barrows and gilts (P > 0.05). Total radioactive and parent residues declined in tissues as withdrawal period increased. After the 0-d withdrawal period, total liver residues (286 ppb) were approximately equal to lung residues, twice those of the kidney, and about 15 times those of adipose tissue and skeletal muscle. After a 7-d withdrawal period, total radioactive residues in liver (15 ppb) were roughly three times greater than lung, kidney, and adipose tissue total residues and about 13 times those of skeletal muscle total residues. Parent clenbuterol represented 79, 63, 42, 67, and 100% of the total radioactive residue in adipose tissue, kidney, liver, lung, and skeletal muscle, respectively, in hogs slaughtered with a 0-d withdrawal period. With increasing withdrawal period, the percentage of total radioactive residue present as parent clenbuterol within edible tissues (including lung) decreased, so that after a 7-d withdrawal period, 7, 16, and 29% of the total residue was composed of parent clenbuterol in kidney, liver, and lung, respectively. After a 7-d withdrawal period, parent clenbuterol exceeded the European maximum residue limit (0.5 ppb) 4.6-fold in liver and 2.4-fold in lung. In muscle, clenbuterol was approximately 40 times the limit after a 0-d withdrawal period but had dropped below 0.5 ppb after a 3-d withdrawal period. Results from this study indicate that clenbuterol HCl is well absorbed in swine and that the use of clenbuterol in this species in an off-label manner is inconsistent with human food safety standards used in developed countries.

Animals↗