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Biomedical subjects

R L Hale

Publications and source records attributed to R L Hale.

At least 19 recordsLinked to original sources
PubMed2000

Anxiety in mice following acute aspartame and ethanol exposure.

The purpose of the present study was to look at the effect of aspartame on the anxiolytic actions of ethanol. Previous research has shown that ethanol reliably produces an anxiolytic effect on rodent's plus-maze performance. There have been anecdotal reports that aspartame increases anxiety. CD-1 male mice were given i.p. aspartame doses of vehicle, 1000, or 2000 mg/kg, followed 30 min later by i.p. ethanol doses of 1.6 g/kg or vehicle. Animals were then placed in an open field, then tested in the plus-maze. Results determined that the aspartame condition had no significant effect on anxiety-related behavior, nor did it alter the anxiolytic actions of ethanol. Thus, acute high dose exposure to aspartame does not appear to affect anxiety-related behaviors.

Animals↗
PubMed1998

Screening for novel antimicrobials from encoded combinatorial libraries by using a two-dimensional agar format.

A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.

Bacillus subtilis↗
PubMed1995

Production responses to various doses and ratios of estradiol benzoate and trenbolone acetate implants in steers and heifers.

At each of three locations, 400 steers and an equal number of heifers were randomized to 10 treatment groups. The purpose of the studies was to evaluate the response of feedlot steers and heifers to single implants containing a combination of estradiol benzoate (EB) and trenbolone acetate (TBA) at two different ratios each at three doses. The selected ratios corresponded to 1E2(estradiol-17 beta):5TBA and 1E2:10TBA. The two ratios were each tested at three different EB/TBA doses (1:5 at 20/70, 40/140, and 60 mg/210 mg, 1:10 and 14/100, 28/200, and 42 mg/300 mg). The test groups were compared to those given each of the compounds alone (60 mg of EB or 300 mg of TBA), as well as to groups reimplanted with Synovex S or Synovex H implants and untreated controls. Steers (P < .01) and heifers (P < .05) implanted with the 1:10 E2:TBA implants gained faster and had better feed conversion (FC) than their counterparts given 1:5 E2:TBA over the 140-d trial. The results indicated that both estradiol benzoate and trenbolone acetate contributed to the efficacy of the combination implant. Contour plots of ADG and FC indicate that increasing the amount of EB above approximately 36 and 37 mg does not significantly increase the response of steers. The results of these studies indicate that the 28 EB/200 TBA dose is close to optimal for growth promotion and feed conversion in both heifers and steers. In steers, carcass value was increased (P < .01) in all test groups except the group give TBA only. Despite a slight reduction in marbling score and percentage of Choice carcasses, carcasses of steers treated with either 28 mg of EB/200 mg of TBA or 42 mg of EB/300 mg of TBA were more valuable (P < .05) than carcasses from steers in any of the 1:10 ratio EB/TBA groups. Carcass values for groups reimplanted with Synovex S or Synovex H or implanted with EB alone were not significantly different from those for groups implanted with any dose of the 1:10 EB/TBA ratio.

Anabolic Agents↗
PubMed1994

Find your department's rung on the ladder of sophistication.

How highly evolved is your materials management department? Those on the lower rungs of the evolutionary ladder have passive, non-strategic roles and simply react to input from other departments; those that have evolved to higher levels are more active and involved in the organization's strategic decisions.

Decision Making, Organizational↗
PubMed1993

Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal "kindling".

Prior experience with ethanol (EtOH) withdrawal may sensitize an individual to subsequent withdrawal episodes. It has been hypothesized that the progressive intensification of the EtOH withdrawal syndrome following repeated episodes of EtOH intoxication and withdrawal may represent the manifestations of a "kindling" mechanism. The purpose of this study was to develop an animal model of EtOH withdrawal that is sensitive to the effects of prior withdrawal experience. Adult male C3H mice were chronically exposed to EtOH vapor in inhalation chambers prior to withdrawal testing. A multiple withdrawal (MW) group received 3 cycles of 16 hr EtOH vapor separated by 8-hr periods of abstinence; a single withdrawal (SW) group received a single bout of EtOH exposure (16 hr); a third group (SW-CONT) experienced a single withdrawal episode after receiving the equivalent amount of EtOH intoxication as the MW group (16 x 3 = 48 hr), but in a continuous (uninterrupted) fashion; and a fourth group (C) served as controls, not receiving any EtOH exposure throughout the study. Severity of the withdrawal response was assessed by scoring handling-induced convulsions hourly for the first 10 hr and then at 24 hr postwithdrawal. The results indicated that the severity of EtOH withdrawal seizures was significantly greater in animals that had a prior history of withdrawal episodes (MW group) in comparison to a separate group of animals that were tested following a single withdrawal from the same 16-hr intoxication period (SW group).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Withdrawal Delirium↗
PubMed1993

Effects of prenatal ethanol exposure on later sensitivity to the low-dose stimulant actions of ethanol in mouse offspring: possible role of catecholamines.

The purpose of this study was to examine whether prenatal ethanol (EtOH) exposure alters later sensitivity to the low-dose stimulant effects of EtOH. Because the locomotor stimulant effects of EtOH are thought to be mediated, at least in part, by activation of brain monoamine systems, and because prenatal EtOH exposure has been shown to alter brain monoamine activity, it was hypothesized that prenatal EtOH exposure may alter sensitivity to the stimulant actions of EtOH. To test this hypothesis, sensitivity to the locomotor stimulant effects of various challenge doses of EtOH was examined in male and female offspring from prenatal alcohol (A), pair-fed (PF), and lab chow (LC) groups at different ages. In addition, to address the hypothesis further, sensitivity to the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) was examined in these offspring, as well. Results indicated that male offspring prenatally exposed to EtOH exhibited reduced baseline activity and a blunted stimulant response to all challenge doses of EtOH (0.75-1.5 g/kg) in comparison with control offspring at 30 days of age, but these effects appeared to "normalize" at 70 days of age. Female EtOH-exposed offspring also exhibited a reduced baseline level of activity relative to control offspring, as well as a blunted stimulant response to the lowest challenge dose of EtOH (0.75 g/kg) at 30 days of age, and these effects persisted into adulthood. The stimulant response to higher doses of EtOH did not significantly differ among prenatal treatment groups in young or adult female offspring. However, because baseline activity was significantly lower in female EtOH-exposed offspring than control offspring, the stimulant response to these doses of EtOH (1.125 and 1.5 g/kg) was relatively greater than that for PF and LC offspring. Importantly, none of the differences in performance among the prenatal treatment groups could be attributed to an alteration in EtOH pharmacokinetics, because blood EtOH levels measured immediately following the 10-min test session were similar for all prenatal treatment groups across all of the EtOH test doses. Further, a similar response profile as that observed following EtOH challenge at 70 days of age was obtained following phenobarbital challenge (10-40 mg/kg). Finally, whereas AMPT (50-400 mg/kg) dose-dependently antagonized the stimulant effects of EtOH in all prenatal treatment groups, this effect of AMPT was significantly greater in mice prenatally exposed to EtOH in comparison with control offspring.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1992

Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin, which inhibit prostaglandin (PG) synthesis, have a pronounced effect on a broad range of ethanol (EtOH) actions. Given this, it is somewhat surprising that NSAID treatment has not been found to alter major signs of ethanol withdrawal. To date, the only effect found has been indirect, that is, NSAID treatment reduces the efficacy of PG precursor administration in the treatment of ethanol withdrawal via the inhibition of PG formation. However, in those studies reporting negative results NSAID administration was delayed until EtOH withdrawal. Studies demonstrating NSAID-related attenuation of other actions of EtOH have typically employed a pretreatment paradigm in which NSAIDs are administered prior to, not after, ethanol exposure. Thus, it may be that the point in the ethanol exposure/withdrawal episode at which NSAIDs are administered could be crucial in determining their effects of the ethanol withdrawal syndrome. To address this issue, we employed a multiple-exposure "binge drinking" model. On each of 6 treatment days, male BALB/c mice were injected subcutaneously with either acetylsalicylic acid (ASA, 150 mg/kg) or the buffer vehicle, followed 1 h later by either ethanol (4.0 g/kg) or saline (0.9%) by gavage. Ethanol withdrawal severity, as measured by handling-induced convulsions, was determined 2, 4, 6, 8, 10, 12, and 24 h after EtOH gavage. ASA pretreatment was found to significantly reduce handling-induced convulsions in ethanol-intubated animals. In fact, the attenuation was of such a magnitude that the ASA-pretreated ethanol group did not significantly differ in withdrawal severity from non-ethanol-exposed controls. This effect was not likely due to ASA-related alterations in ethanol pharmacokinetics. These findings have relevance for the understanding of the basic mechanisms underlying ethanol dependence, as well as the potential role of PGs in this phenomenon.

Alcoholism↗
PubMed1991

Aspirin dose-dependently reduces alcohol-induced birth defects and prostaglandin E levels in mice.

The purpose of the present study was threefold. The first purpose was to determine if aspirin (ASA) decreases alcohol-induced birth defects in mice in a dose-dependent fashion. The second purpose was to see if the antagonism of alcohol-induced birth defects afforded by ASA pretreatment was related to dose-dependent decreases in prostaglandin E (PGE) levels in uterine/embryo tissue. The third purpose was to determine if ASA pretreatment altered maternal blood alcohol level. In experiments 1 and 2, pregnant C57BL/6J mice were administered ASA (0, 18.75, 37.5, 75, 150, or 300 mg/kg) on gestation day 10. One hour following the subcutaneous injection of ASA, mice received alcohol (5.8 g/kg) or an isocaloric sucrose solution intragastrically. In experiment 1 the incidence of birth defects was assessed in fetuses delivered by caesarean section on gestation day 19. In experiment 2 uterine/embryo tissue samples were collected on gestation day 10 1 hr following alcohol intubation for subsequent PGE analysis. In experiment 3 blood samples were taken at five time points following alcohol intubation from separate groups of alcohol-treated pregnant mice pretreated with 150 mg/kg ASA or vehicle. The results from the three experiments indicated that 1) ASA dose-dependently reduced the frequency of alcohol-induced birth defects in fetuses examined at gestation day 19, (2) ASA decreased the levels of PGE in gestation day 10 uterine/embryo tissue in a similar dose-dependent fashion, and 3) ASA pretreatment did not significantly influence maternal blood alcohol levels. These results provide additional support for the hypothesis that PGs may play an important role in mediating the teratogenic actions of alcohol.

Abnormalities, Drug-Induced↗
PubMed1991

RO15-4513 antagonizes the anxiolytic effects of ethanol in a nonshock conflict task at doses devoid of anxiogenic activity.

RO15-4513 is a partial benzodiazepine inverse agonist that has been reported to antagonize some of the biochemical and neurobehavioral actions of ethanol. However, whether this antagonistic action of RO15-4513 is dependent on the drug exerting its intrinsic (inverse agonist) properties is unclear at present. The purpose of the present study was to examine whether RO15-4513 was capable of antagonizing the anxiolytic effects of ethanol in a nonshock conflict task at doses that, by themselves, do not reveal the compound's intrinsic anxiogenic properties. The consummatory conflict task employed (negative contrast) involves quantifying how animals respond to an abrupt, unexpected reduction in reward (sucrose solution), and is particularly sensitive to the effects of anxiolytic agents, including ethanol. As previously demonstrated, depressed consummatory behavior engendered by reward reduction was significantly alleviated by ethanol (0.75 g/kg). This anxiolytic effect of ethanol, however, was antagonized dose dependently by RO15-4513 (0.1875-3.0 mg/kg). Only the highest dose of RO15-4513 (3.0 mg/kg) showed evidence of further response suppression. Lower doses of RO15-4513 tested did not exert an anxiogenic effect when given alone. Thus the antagonism of EtOH's anxiolytic (contrast-reducing) effects occurred at doses of RO15-4513 (0.375-1.5 mg/kg) that did not exhibit any intrinsic anxiogenic activity. As such, these results suggest that RO15-4513 interacts with the anxiolytic effects of ethanol in a nonadditive fashion in this test situation.

Animals↗
PubMed1990

Indomethacin does not antagonize the anxiolytic action of ethanol in the elevated plus-maze.

The present study was designed to examine whether the prostaglandin (PG) synthesis inhibitor indomethacin (INDO) could antagonize the anxiolytic effects of ethanol (EtOH) in the elevated plus-maze test of anxiety. EtOH (1.6 g/kg) significantly increased the percentage of open arm entries and time spent on the open arms in both inbred C57BL/6J and outbred CD-1 mouse strains. However, this anxiolytic effect of EtOH was not significantly antagonized by pretreatment with INDO (5 and 10 mg/kg) in either strain. EtOH also significantly increased total arm entries in CD-1 mice, but not in the C57BL/6J strain. These data from C57BL/6J mice indicate that the low-dose stimulant properties of EtOH can be dissociated from the anxiolytic action of the drug in the plus-maze task. Finally, although INDO did not antagonize the stimulant effect of EtOH in the plus-maze task (in CD-1 mice), it did attenuate EtOH-induced stimulation of locomotor activity in an open-field arena. Taken together, these results suggest some specificity with regard to the role of PGs in mediating (or modulating) the neurobehavioral actions of EtOH, and further support the notion that the anxiolytic and stimulant effects of EtOH may be mediated by different mechanisms.

Animals↗
PubMed1989

Ethanol-induced locomotor stimulation in C57BL/6 mice following RO15-4513 administration.

The purpose of this study was to examine the effects of two partial benzodiazepine inverse agonists, RO15-4513 and FG-7142, alone and in combination with ethanol on locomotor activity in C57BL/6 mice. When administered alone, 1.5 g/kg ethanol did not significantly influence activity, confirming previous reports indicating this mouse strain is relatively insensitive to the excitatory properties of ethanol. RO15-4513 treatment also did not significantly influence locomotor activity when administered alone. However, coadministration of RO15-4513 (1.5-6 mg/kg) and ethanol markedly increased locomotor activity. Moreover, the unmasking of ethanol's stimulant action by RO15-4513 (6 mg/kg) was completely reversed by pretreatment with the benzodiazepine receptor antagonist RO15-1788. In contrast, FG-7142 (10-20 mg/kg) increased activity to the same extent in both saline and ethanol-injected mice. This effect was blocked by RO15-1788 pretreatment as well. Neither RO15-4513, FG-7142, nor RO15-1788 significantly influenced blood ethanol concentrations. It is suggested that RO15-4513 unmasked the stimulant effects of ethanol by virtue of its ability to antagonize the depressant properties of ethanol in C57BL/6 mice.

Animals↗
PubMed1989

Contributions of hippocampus and neocortex to the expression of ethanol effects.

The distinctive effects of ethanol on behavior suggest that certain parts of the CNS may be especially sensitive to it. One of the primary candidates is the hippocampal formation. Damage to this structure mimics acute ethanol treatment across a wide variety of behavioral tasks and processes. The possibility of a hippocampal basis for ethanol psychopharmacology was examined in the present experiments. Chosen for behavioral analysis were relatively complex eight-arm radial maze tasks which have independently been shown to be sensitive to ethanol administration and hippocampal lesions. Measures included arm selection predictability, vigilance, and retardation of extinction. Bilateral hippocampal lesions or ethanol injection (1.5 g/kg, IP) produced similar effects. However, hippocampectomy did not disrupt ethanol's influence on any task. Comparatively, neocortical ablation, especially prefrontal, was quite effective in this respect. It blocked or reduced two of the drug's three behavioral effects examined here, without any strong influence of its own, and without altering blood alcohol concentration.

Animals↗
PubMed1988

Sampling behavior in the radial maze and operant chamber: role of the hippocampus and prefrontal area.

Rats were observed in the radial maze and in an operant setting where "errors" were, within limits, impossible to commit. Under these circumstances, the animals were free to seek information from the environment by varying their behavior, if they chose to do so, without penalty of nonreward. Rats with hippocampal, but not prefrontal or parietal damage, sampled fewer successive arm choices in the maze and exhibited a greatly reduced sensory analysis of the maze and its context. In operant chambers equipped with multiple levers, only hippocampal lesion narrowed the variety of interresponse intervals, which resulted in rhythmic responding. In contrast, the distribution of responses across the three response targets was not influenced by central nervous system injury. This pattern of information deprivation imposed by the hippocampal lesion parallels the profile of performance of such animals on more conventional tasks that depend on such information for optimal performance. Importantly, the sampling deficits were not direct outcomes of the hippocampal damage. Close scrutiny revealed that the rigidity developed over time, albeit quite rapidly. Thus the narrowed behavioral variation following hippocampectomy depends on some interactive component of task experience. We argue that reward is the other critical ingredient.

Animals↗
PubMed1988

Subject selection biases in alcoholic samples: effects on cognitive performance.

The effects of subject selection bias in research on cognitive deficits in sober alcoholics were studied in a sample of 523 subjects (98 controls, 276 ineligible alcoholics, 40 eligible alcoholics who declined to participate, and 144 eligible and participatory alcoholics). All subjects received the Shipley Institute of Living Scale (Vocabulary and Abstracting subscales) and measures of anxiety, depressive symptoms, childhood hyperkinesis and attentional deficit disorders were obtained. Results indicate that current guidelines for alcoholic subject selection are biasing analyses toward support of the null hypothesis. Declined alcoholics performed more poorly on the Shipley Abstracting than did the "Used" group, yet did not differ significantly from the Used alcoholic groups on depression or anxiety. Declined alcoholics did, however, report significantly fewer Hk/MBD symptoms than did other alcoholic groups. ANCOVAs that used the affective and childhood disorders as covariates did not alter the differences in cognitive performance described above.

Adult↗
PubMed1986

Neonatal aldosterone administration alters later response to adrenalectomy and aldosterone infusion in the rat.

Juvenile and adult infusions of mineralocorticoids promote weight gains in rats. However, nothing is known about the effects of very early administration. As such treatments often bring about enduring changes, we examined the impact of neonatal (days 1-5 of life), followed by early adult (days 45-57 of life), administration of aldosterone (ALDO) on the weight gains of free-fed rats. Analysis revealed that neonatal ALDO exposure altered the pattern of weight gain during the later period. Specifically, acute neonatal exposure increased weight gain in adrenalectomized young adult rats. At the same time, it appeared to reduce the effects of chronic ALDO exposure in these animals.

Adrenalectomy↗
PubMed1984

Profile analysis of a referral sample.

This investigation demonstrates the use of Skinner's Modal Profile Analysis technique to uncover the underlying classification structure in a group of children (n = 235) referred for psychological evaluations by their public school teachers. Data were acquired on children's intellectual development, academic achievement, and social adjustment. The profile solution identifies three profiles of children with each profile containing two distinct types. Thus, six types (groups) were identified. This three-profile (six-group) solution is able to classify 81% of the referral sample. However, the statistical solution to the classification question did not correspond to the system by which the children were classified in their respective schools. While a discriminant analysis using profile elevation, scatter, and shape scores as the predictor variables and the child's classification in the school as the criterion of interest indicates a statistically significant ability to predict the child's school label, for all practical purposes the predictive ability is not useful.

Affective Symptoms↗
PubMed1982

Validation of a systems-actuarial computer process for multidimensional classification of child psychopathology.

Tested diagnostic classifications of child psychopathology produced by a computerized technique known as multidimensional actuarial classification (MAC) against the criterion of expert psychological opinion. The MAC program applies series of statistical decision rules to assess the importance of and relationships among several dimensions of classification, i.e., intellectual functioning, academic achievement, adaptive behavior, and social and behavioral adjustment, to perform differential diagnosis of children's mental retardation, specific learning disabilities, behavioral and emotional disturbance, possible communication or perceptual-motor impairment, and academic under- and overachievement in reading and mathematics. Classifications rendered by MAC are compared to those offered by two expert child psychologists for cases of 73 children referred for psychological services. Experts' agreement with MAC was significant for all classification areas, as was MAC's agreement with the experts held as a conjoint reference standard. Whereas the experts' agreement with MAC averaged 86.0% above chance, their agreement with one another averaged 76.5% above chance. Implications of the findings are explored and potential advantages of the systems-actuarial approach are discussed.

Achievement↗