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Biomedical subjects

G A Rockwood

Publications and source records attributed to G A Rockwood.

13 recordsLinked to original sources
PubMed1994

Efficacy of tacrine as a nerve agent pretreatment.

Tacrine (THA) was evaluated in vitro and in vivo as a pretreatment for nerve agent intoxication. In vitro experiments showed that the primary effect of THA was direct inhibition of purified fetal bovine serum acetylcholinesterase (AChE) with a slight effect on slowing the aging rate of nerve agent-inhibited AChE. THA produced significant behavioral effects at doses above 1.7 mg/kg, i.m., in the mouse and 3.4 mg/kg, i.m., in the guinea pig. At the no observable effect level (NOEL) for mice (1.7 mg/kg), THA was effective (P < or = 0.05) in reducing tabun- and soman-, but not sarin-induced lethality in mice. Experiments in the guinea pig showed that at the NOEL (3.4 mg/kg, i.m.) THA was not effective in decreasing lethality due to soman exposure. Since there was significant overlap between pharmacologically effective doses of THA and those which produce behavioral toxicity, THA was not considered a suitable pretreatment for nerve agent intoxication.

Acetylcholinesterase↗
PubMed1990

High-fat diet preference in developing and adult rats.

Diet preference tests in rats have yielded equivocal results, as some investigators have reported a strong preference for diets high in fat over those containing less fat, while others have failed to see this preference. To further explore this unresolved problem, two diet preference experiments were conducted. In Experiment 1, adult rats were maintained for at least three months on one of three powdered diets (control, high-carbohydrate or high-fat). Rats were then given a preference test with all three diets available. Animals from each group overwhelmingly preferred the high-fat diet. To determine whether this preference was also present in younger, developing rats, in Experiment 2, weanling animals were tested with the same three diets as in Experiment 1. As observed with adult animals, weanling rats also showed a strong preference for the high-fat diet. The idea that rats prefer a diet with a relatively high level of fat is supported. Possible explanations for these findings are discussed.

Aging↗
PubMed1988

Bovine leukocyte interferon: characterization and large-scale production.

Natural bovine leukocyte interferon (IFN) was produced in high titer (15,314 U/ml), with Sendai virus as the inducer at 300 hemagglutinating units (HA)/ml and 12 h incubation. Its antiviral activity was completely stable for 30 days at 4 degrees C, -20 degrees C, or -70 degrees C, and 96 h at 37 degrees C, but some activity was lost after 15 min at 56 degrees C. All activity was lost after treatment with trypsin, but pH 2.0 dialysis had no effect. Bovine leukocyte IFN inhibited growth of bovine kidney cells in tissue culture. The system reported could be used to produce bovine leukocyte IFN in quantities sufficient for clinical use in cattle.

Animals↗
PubMed1988

Kinetics of large-scale production of bovine leukocyte interferon, using three viral inducers.

Kinetics of large-scale production of naturally derived bovine leukocyte interferon (IFN) was investigated using Sendai virus, Newcastle disease virus, and infectious bovine rhinotracheitis virus inducers. Cultures were tested for IFN production every 6 hours for 66 hours. The effect of varying the priming dose of Sendai virus from 0 to 50% of total virus dose and the effect of varying the priming time from 0 to 4 hours before induction also were investigated. Other factors explored were effects of varying the fetal bovine serum concentration (from 0 to 8%) and individual cow donors on bovine IFN titers. Highest bovine leukocyte IFN titers (15,314 U/ml) were obtained using Sendai virus (priming dose, 60 hemagglutinating units/ml; inducing dose, 240 hemagglutinating units/ml) and incubating for 12 hours. Up to 24 L (over 360 million U) of naturally derived leukocyte IFN were produced at one time.

Animals↗
PubMed1987

Prenatal alcohol exposure: recent work on behavioral dysfunctions in pre-weanling rats.

This article reviews recent data collected in our laboratory examining the behavioral effects of prenatal alcohol exposure in pre-weanling rats. The behavioral alterations which are discussed include suckling dysfunctions, overactivity, and early learning deficits. Similar behavioral dysfunctions have also been reported in children exposed to alcohol during prenatal development. These similarities are discussed as well as possible insights that might be gained from animal models of fetal alcohol effects.

Animals↗
PubMed1986

Suckling deficits in rat pups exposed to alcohol in utero.

With the aid of a pair-feeding procedure, two groups of pregnant Long-Evans rats were fed a liquid diet containing 35% or 0% ethanol-derived calories during days 6-20 of gestation. A third group was allowed free access to standard lab chow and water throughout pregnancy. At 6-7 or 9-10 days of age, suckling performance by male and female offspring representing the three prenatal treatment groups was examined. The test stimulus was a 6-10-day postparturient, anesthetized dam in which milk letdown was prevented. Compared to both pair-fed and lab chow controls, alcohol-exposed animals exerted a lower maximum suckling pressure, spent less time suckling during the test session, and displayed an altered suckling pattern. These data are consistent with existing clinical and experimental evidence documenting sucking deficits following prenatal alcohol exposure and are discussed in terms of prenatal alcohol-induced CNS impairment.

Age Factors↗
PubMed1982

Naloxone modifies sugar-water intake in rats drinking with open gastric fistulas.

The effects of the opiate antagonist naloxone (NX) on fluid preference and intake were determined in rats drinking with chronically indwelling gastric fistulas. The subjects were tested both after 22.5 hr fluid deprivation, and no deprivation, with open fistulas (sham drinking), as well as with closed fistulas. Following an injection of either saline or NX (0.5-10.0 mg/kg, administered SC), or no injection, the subjects were given the choice to drink water or 10% sucrose, in a two-bottle test, for 1 hr/day. With open fistulas, and following fluid deprivation, the animals sham drank both sucrose and water, but had a strong preference for sucrose. When not fluid deprived, the same animals sham drank sucrose almost exclusively. NX significantly reduced sucrose intake by the sham drinking animals, in both the deprived and not deprived conditions, but did not modify fluid preference. These data support the idea that NX modifies affective reactivity to palatable solutions, and that NX's antidipsogenic actions are not due to feedback from post-absorptional events.

Animals↗
PubMed1981

Intracerebral administration of naloxone and drinking in water-deprived rats.

In 24-hr water-deprived rats, naloxone, at various doses (0, 12.5, 25, 50 micrograms/rat), was administered prior to a 15-min drinking period. Infusions were made bilaterally into each lateral ventricle, frontal cortex, lateral preoptic area, lateral hypothalamus, and caudate nucleus. Naloxone reliably reduced water consumption at 50 micrograms/rat when infused into the lateral ventricles and lateral hypothalamic areas. When comparable doses of naloxone were given by peripheral injection, no effect on drinking was observed. There appeared to be a trend developing for greater sensitivity to naloxone when infusions were made into a particular part of the hypothalamus. These data support the idea that naloxone reduces drinking by acting at central opiate receptors.

Animals↗
PubMed1981

Naloxone reduces fluid intake in rats with open gastric fistulas.

Water-deprived rats, fixed with chronically indwelling gastric fistulas, drank with the fistulas open (sham drinking) for 20 min. The subjects were given three doses of naloxone (0.0, 1.0, and 10 mg/kg, SC) 15 min before the opportunity to sham drink. The mean water intakes on days of 0.0, 1.0 and 10 mg/kg of naloxone were 43.3, 36.3 and 23.1 g, respectively. Naloxone clearly reduced fluid intake in rats engaged in sham drinking. This finding, that naloxone reduces fluid intake when post-ingestional absorption is prevented, lends support to the idea that naloxone modified central neural regulatory processes. The results of these experiments do not support the hypothesis that the endorphins are involved exclusively with drive-reduction.

Animals↗
PubMedDate not supplied

In vitro and in vivo comparison of sulfur donors as antidotes to acute cyanide intoxication.

Antidotes for cyanide (CN) intoxication include the use of sulfane sulfur donors (SSDs), such as thiosulfate, which increase the conversion of CN to thiocyanate by the enzyme rhodanese. To develop pretreatments that might be useful against CN, SSDs with greater lipophilicity than thiosulfate were synthesized and assessed. The ability of SSDs to protect mice against 2LD50 of sodium cyanide (NaCN) administered either 15 or 60 min following administration of an SSD was assessed. To study the mechanism of action of the SSD, the candidate compounds were examined in vitro for their effect on rhodanese and 3-mercaptopyruvate sulfurtransferase (MST) activity under increasing SSD concentrations. Tests were conducted on nine candidate SSDs: ICD1021 (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide dihydrochloride), ICD1022, (3-hydroxypyridin-2-yl N-[(N-methyl-3-aminopropyl)]-2-aminoethyl disulfide trihydrochloride), ICD1584 (diethyl tetrasulfide), ICD1585 (diallyl tetrasulfide), ICD1587 (diisopropyl tetrasulfide); ICD1738 (N-(3-aminopropyl)-2-aminoethyl 2-oxopropyl disulfide dihydrochloride), ICD1816 (3,3'-tetrathiobis-N-acctyl-L-alanine), ICD2214 (2-aminoethyl 4-methoxyphenyl disulfide hydrochloride) and ICD2467 (bis(4-methoxyphenyl) disulfide). These tests demonstrated that altering the chemical substituent of the longer chain sulfide modified the ability of the candidate SSD to protect against CN toxicity. At least two of the SSDs at selected doses provided 100% protection against 2LD50 of NaCN, normally an LD99. All compounds were evaluated using locomotor activity as a measure of potential adverse behavioral effects. Positive hypoactivity relationships were found with several disulfides but none was found with ICD1584, a tetrasulfide. Separate studies suggest that the chemical reaction of potassium cyanide (KCN) and cystine forms the toxic metabolite 2-iminothiazolidine-4-carboxylic acid. An alternative detoxification pathway, one not primarily involving the sulfur transferases. may be important in pretreatment for CN intoxication. Although studies to elucidate the precise mechanisms are needed. it is clear that these newly synthesized compounds provide a new rationale for anti-CN drugs, with fewer side-effects than the methemoglobin formers.

Animals↗
PubMedDate not supplied

Effects of scopolamine on spontaneous alternation and shuttle avoidance in rats exposed to alcohol in utero.

The behavioral effects of the anticholinergic scopolamine were examined in rats exposed to alcohol prenatally. Pregnant Long-Evans rats received isocaloric liquid diets containing either 35% or 0% ethanol-derived calories on Days 6-20 of gestation. A pair-feeding procedure was used, and a lab chow control group was also included. In Experiment 1, adult offspring were tested on a spontaneous alternation task following 1 mg/kg scopolamine or saline. Independent of prenatal treatment, scopolamine caused an increase in the number of trials to alternate. In Experiment 2, offspring were tested on a two-way shuttle avoidance learning task following a 1 mg/kg injection of scopolamine or methylscopolamine. Alcohol-exposed animals injected with methylscopolamine made fewer avoidances than controls on the second day of testing while treatment with scopolamine enhanced avoidance performance to control levels. These data suggest that prenatal exposure to alcohol does not interfere with scopolamine-induced changes in the behavior of adult rats.

Animals↗
PubMedDate not supplied

Nipple attachment behavior in rat pups exposed to alcohol in utero.

Two experiments were conducted to further characterize impaired nipple attachment behavior in 5-day-old rat pups exposed to alcohol prenatally. In Experiment 1, animals were given two different nipple attachment tests. In the pups-on-mother test, which required animals to first locate a nipple, alcohol-exposed pups displayed longer attachment latencies than controls. Furthermore, more than 50% of these pups failed to attach during testing. In the pups-on-nipple test, in which no search for the nipple was necessary, prenatal alcohol did not reliably affect attachment. To assess the extent to which alcohol-exposed pups utilize an olfactory cue for attachment, in Experiment 2, nipple attachment was observed using the pups-on-nipple test before and after olfactory cue removal. Similar to controls, the alcohol-exposed animals only attached to the normally scented nipples. Therefore, prenatal alcohol exposure impaired nipple search performance in young rats, but not attachment once at the nipple. Moreover, these pups performed like controls in response to olfactory cue manipulation. Possible mechanisms for the poor search behavior are discussed.

Animals↗