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Biomedical subjects

S G Gilbert

Publications and source records attributed to S G Gilbert.

At least 37 records · Page 2Linked to original sources
PubMed1988

Adverse pregnancy outcome in the monkey (Macaca fascicularis) after chronic caffeine exposure.

Caffeine and the related methylxanthine theophylline are consumed regularly by pregnant women. In a study originally designed to assess the neurotoxic potential of caffeine in the infant, 40 female monkeys (Macaca fascicularis) were divided into three groups and administered caffeine in their drinking water at concentrations equivalent to 0, 10 to 15 or 25 to 35 mg/kg/day of caffeine 7 days a week. After a period of adaptation to caffeine these monkeys were mated with untreated males. Reproductive failure in the form of stillbirths and miscarriages was observed in the treated groups. Subsequently, 12 control monkeys and 1 low-dose monkey were added to the study and most of the original monkeys rebred. The second round of pregnancies confirmed that the treated monkeys had an increased rate of stillbirths and miscarriages. The precise cause of death of the stillborn infants could not be determined. Maternal weight gain and infant birth weights decreased in a dose-related manner. These results indicate that in utero exposure to methylxanthines (caffeine and/or its major metabolite theophylline) adversely affects pregnancy outcome in the monkey.

Abortion, Veterinary↗
PubMed1987

Low-level lifetime lead exposure produces behavioral toxicity (spatial discrimination reversal) in adult monkeys.

Cynomolgus monkeys (Macaca fascicularis) were dosed from birth with 0, 50, or 100 micrograms/kg/day of lead. This regimen resulted in blood lead concentrations of 3, 15, or 25 micrograms/dl, respectively, before withdrawal of infant formula at 200 days of age. Blood lead concentration declined thereafter over the next 100 to 150 days to steady-state concentrations of 3, 11, or 13 micrograms/dl. At 9 to 10 years of age, these monkeys were tested on a series of spatial discrimination reversal problems. The monkey was required to respond on the right-most of two push buttons in order to receive a fruit-juice reward. When the task was learned, the left-most button became correct for a total of 15 such reversals on each of three tasks. The stimuli for the first task included no irrelevant cues, the second task included irrelevant form cues, and the third task included irrelevant form and color cues. Treated monkeys were impaired relative to controls in the presence but not in the absence of irrelevant cues. Moreover, the lower dose group was impaired only during the first task after the introduction of irrelevant stimuli, but not after irrelevant stimuli were familiar. These findings represent behavioral impairment in adult monkeys as a result of lifetime lead exposure resulting in blood lead concentrations that are typical for humans in industrialized environments.

Animals↗
PubMed1987

Sensory testing in non-human primates.

Sensory testing in non-human primates can be used to detect subtle sensory toxicity of chemicals. Examples are given covering the determination of spatial contrast sensitivity in monkeys exposed to methyl mercury as an example of visual psychophysics, and the assessment of vibration sensitivity in monkeys exposed to acrylamide, as an example of somatosensory psychophysics.

Acrylamides↗
PubMed1987

Fatal pneumococcal meningitis in a colony-born monkey (Macaca fascicularis).

This report describes the clinical course and pathological findings in a four-year-old male cynomolgus monkey (Macaca fascicularis) which succumbed to fulminant pneumococcal meningitis. The extremely rapid course of this infection emphasizes the importance of early recognition of the clinical manifestations of meningitis in the correct diagnosis and rapid treatment of the condition.

Animals↗
PubMed1986

Elimination of chronically consumed caffeine in the pregnant monkey (Macaca fascicularis).

Characterization of alterations in caffeine elimination during pregnancy is essential in assessing the potential exposure of the fetus to caffeine and its metabolites. Female monkeys (Macaca fascicularis) were exposed to caffeine in their drinking water 7 days/week before, during and after pregnancy. The low exposure (0.15 mg/ml) corresponded to a level sometimes consumed by pregnant women (10-15 mg/kg/day) whereas the high exposure (0.35 mg/ml) was above average human consumption (25-30 mg/kg/day). Blood samples and 24-hr urine samples were collected every 2 weeks throughout dosing. Caffeine and metabolite concentrations in serum and urine were determined by high-performance liquid chromatography. Before pregnancy, geometric mean serum caffeine concentrations were approximately 1.6 and 4.9 micrograms/ml and serum theophylline concentrations were 6.6 and 13.3 micrograms/ml for the low and high dose groups, respectively. During pregnancy, serum caffeine concentrations increased by approximately 100% for both dose groups and, after parturition, declined to prepregnancy concentrations. Serum theophylline concentrations were usually greater than serum caffeine concentrations and did not change during pregnancy. The amount of caffeine and theophylline excreted in the urine over 24 hr increased during pregnancy and returned to prepregnancy levels after parturition. The results of this study indicate that pregnancy decreased caffeine elimination, resulting in a significant increase in serum caffeine levels. The changes in caffeine elimination may be related to alterations in serum estrogen and progesterone levels.

Animals↗
PubMed1985

Low lead exposure from birth produces behavioral toxicity (DRL) in monkeys.

Cynomolgus monkeys (Macaca fascicularis) were dosed from birth with 100, 50, or 0 micrograms/kg/day of lead. This treatment resulted in blood lead concentrations of 25, 15, or 3 micrograms/dl, respectively, before withdrawal of infant formula at 200 days of age, and steady-state concentrations of 13, 11, or 3 micrograms/dl. At approximately 3 years of age, monkeys were tested on an intermittent schedule, differential reinforcement of low rate (DRL). This schedule required the monkey to withhold responding for a specific time in order to be reinforced. The performance of treated monkeys did not improve as rapidly as controls as measured by increase in reinforced responses and decrease in nonreinforced responses during initial sessions. In addition, treated monkeys exhibited greater between session variability during terminal sessions. These effects were dose related. The results of the present experiment in conjunction with those of previous experiments with this same group of monkeys suggest that blood lead concentrations presently found routinely in the human population may produce neurotoxicity.

Animals↗
PubMed1985

Acute trimethyltin intoxication in the monkey (Macaca fascicularis).

Adult cynomolgus monkeys were administered trimethyltin (TMT) iv in dosages ranging from 0.75 to 4.0 mg TMT/kg and observed for behavioral changes. Animals were subsequently killed for light and electron microscopic examination. TMT showed a dose-related toxicity, with high dose animals (4.0 and 3.0 mg/kg) dying within 24 hr, and low dose animals (0.75 mg/kg) surviving without morphological effects. Animals given 1.10 mg TMT/kg displayed a reproducible clinical course, characterized by tremor, hyperactivity, and ataxia which progressed to stupor and finally unconsciousness. By light microscopy, neuropathology was most pronounced in the CA-3 and CA-4 regions of Ammon's horn. Degenerating pyramidal neurons, micro- and astrogliosis, and neuronophagia were commonly observed. Mild degenerative changes were identified in amygdala, medulla, spinal cord, and Purkinje cells. The fascia dentata remained intact. Ultrastructurally, injured neurons contained accumulations of lysosomes and lysosome-like structures within perikarya and neurites. Demyelination or vascular damage was not observed. Data indicate the monkey to be highly sensitive to TMT, with morphological injury most severe in limbic structures.

Animals↗
PubMed1985

The fate of chronically consumed caffeine in the monkey (Macaca fascicularis).

The metabolic fate of chronically administered caffeine was examined in monkeys. Caffeine and equal parts of citric acid were added to the drinking water of four female monkeys (Macaca fascicularis). The concentration was gradually increased over a 10-week period to 0.35 mg/ml for three of the monkeys. A monkey that was lactating, but had no infant, was exposed to caffeine in the drinking water at a concentration of 0.30 mg/ml. At these doses, administered for up to 50 weeks, there were no overt signs of toxicity as indicated by food and fluid consumption, body weight, or general condition of the monkey. Mean plasma caffeine concentrations were 3.8, 5.7, and 5.9 micrograms/ml, while mean plasma theophylline concentrations were 11.8, 13.0, and 20.1 micrograms/ml, respectively for the monkeys receiving 0.35 mg/ml. Mean plasma caffeine and theophylline concentrations for the lactating monkey were 10.7 and 21.4 micrograms/ml, while mean milk concentrations were 10.5 and 17.6 micrograms/ml, respectively, indicating that caffeine and its major metabolite theophylline are readily excreted in milk. The high plasma theophylline levels indicate that caffeine metabolism in the monkeys differs from that in humans. Theophylline was the main urinary metabolite. In addition, large amounts of 1.3-dimethyluric acid were excreted in the urine but only traces of this metabolite were found in the plasma. After withdrawal of caffeine, plasma caffeine levels decreased to almost zero in the first 24 hr with a half-life of 5.5 hr, and plasma theophylline levels declined with a half-life of 12.7 hr.

Animals↗
PubMed1985

Effect of diet on blood lead concentration in the cynomolgus monkey.

Infant cynomolgus monkeys (Macaca fascicularis) were reared from birth in an infant primate nursery and dosed with lead acetate (2 mg Pb/kg body wt/day) from approximately 100 days of age. The monkeys were switched from an infant formula diet to a diet of primate chow and water at 460 days of age. Beginning at approximately 935 days of age, various diets were fed in the following order: infant formula plus a restricted amount of primate chow, infant formula only, infant formula plus cellulose fiber, infant formula plus phytic acid, cow's milk, and primate chow plus water. Blood lead content was determined throughout the experiment. At 360 days of treatment (approx. 460 days of age) the blood lead concentration was 90 micrograms/dl but decreased to 50 micrograms/dl within 30 days after the diet was changed to primate chow and water. When the monkeys were 935 days of age the introduction of the infant formula plus a restricted amount of primate chow had little effect on blood lead concentrations. However, when primate chow was removed from the diet so that the monkeys were fed infant formula only, there was a rapid increase in blood lead from approximately 40 to 220 micrograms/dl. The addition of cellulose fiber to the infant formula had no effect on blood lead concentrations, whereas the addition of phytic acid caused an abrupt decrease to approximately 85 micrograms/dl. Blood lead concentrations increased to approximately 190 micrograms/dl when cow's milk only was fed and decreased to approximately 55 micrograms/dl when the monkeys were returned to a diet of primate chow and water.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Automated high-performance liquid chromatographic assay for monitoring caffeine and its metabolites in biological fluids of monkeys consuming caffeine.

A recently reported high-performance liquid chromatographic procedure, using a 5 micron C18 reversed-phase column to separate and quantitate caffeine and seven of its metabolites was modified for use with an automatic sampler to allow the continuous analysis of a large number of samples of various biological fluids obtained from monkeys consuming caffeine. The sensitivity for most metabolites was in the range of 0.1-0.3 microgram/ml from a 0.1 ml sample. The repeatability of the method regarding within-day variations was excellent and the absolute retention time for eight standards differed by less than +/- 0.03 min. Excellent repeatability in the day-to-day assay, with almost quantitative recoveries, was found for most of the analyzed compounds in various biological fluids. The standard deviation for the quantitation of all standards was in a range of 0.41-2.01 micrograms/ml, with the standard error less than 0.02. Using this method an analytical chemist could process between 40 and 60 samples of biological fluids in 24 h. The main metabolite of caffeine in the plasma of the monkey was theophylline, while theophylline and 1,3-dimethyluric acid were the major metabolites in urine. A close correlation was observed for the pattern of metabolites found in plasma and milk.

Animals↗
PubMed1982

Early chronic low-level methylmercury poisoning in monkeys impairs spatial vision.

Five monkeys were treated from birth with oral doses of mercury as methylmercury (50 micrograms per kilogram of body weight per day); concentrations in the blood peaked at 1.2 to 1.4 parts per million; and declined after weaning from infant formula to a steady level of 0.6 to 0.9 part per million. There were no overt signs of toxicity. When tested between 3 and 4 years of age under conditions of both high and low luminance, treated monkeys exhibited spatial vision that was impaired compared with that of control monkeys.

Animals↗
PubMed1982

Assessment of the effects of acrylamide, methylmercury, and 2,5-hexanedione on motor functions in mice.

Neurotoxic effects of acrylamide, methylmercury, and 2,5-hexanedione were studied in forth female BALB/c mice. The chemicals were dissolved in distilled water and administered via light-tight drinking bottles. Three control groups were used. The first received distilled water, the second received concentrated saccharin solution to assess the effects of reduced water intake, and the third was maintained on a reduced food diet. Motor functions were quantified by measuring landing foot-spread and rotarod performance. Baseline data were collected before dosing started. Mice were placed, twice weekly, on an accelerating rotarod, and their retention time was recorded. In the landing foot-spread test, the experimenter dropped mice from 15 cm onto a flat, smooth surface once a week. The hindlimb splay was then measured by the examiner. Both experimenter and examiner were unaware of the identity of each group (except of the food deprived group, in the case of the experimenter) during the first exposure. Decreased retention time and increased hindlimb splay were observed in mice after 12 d of exposure to acrylamide. Recovery followed treatment cessation. Increased hindlimb splay preceded an obvious decline of rotarod performance in the group receiving the 10 ppm of methylmercury solution. Mice receiving the 20 and 40 ppm of methylmercury solutions did not display any change in these tests before overt signs of toxicity. 2,6-Hexanedione produced a small decline in performance to a constant level after 85 d of exposure. After dosing termination, performance returned to baseline values. Control groups showed no change in performance on either the rotarod or the landing foot-spread test. Our data show that the rotarod and hindlimb splay tests in mice are about equal in sensitivity to the effects of the neurotoxic chemicals tested.

Acrylamides↗
PubMed1980

Alteration of Acrylonitrile-Methylacrylate-Butadiene Terpolymer by Nocardia rhodochrous and Penicillium notatum.

[C]Barex-210, a terpolymer of acrylonitrile, methylacrylate, and butadiene, was tested for bioconversion. Powdered samples of polymer, each specifically C labeled at different carbon atoms of the polymer, were incubated with either Nocardia rhodochrous or Penicillium notatum in an enriched growth medium for various periods of time. After 6 months of incubation, the C-labeled polymer was transformed from a high-molecular-weight material completely soluble in dimethyl formamide (DMF) into both a lower-molecular-weight form still soluble in DMF and a second form that was no longer soluble in DMF. The amount of C-labeled carbon atoms converted into DMF-insoluble material was 8% of the backbone carbon-carbon atoms and 12% of the side-chain nitrile and acrylate atoms from the acrylonitrile-methylacrylate copolymer and 60% of the elastomer (acrylonitrile-butadiene copolymer) atoms. Metabolism of the polymer was not established from measurements of metabolic CO(2). Evolution of CO(2) amounted to only 0.3, 0.6, 1.8, and 3.3% of these four fractions, respectively. Although the transformation of high-molecular-weight polymer into DMF-insoluble material was rapid in the early stages of microbial growth, the accompanying CO(2) evolution was much slower. Further evidence of polymer alteration was indicated by the infrared spectrum of the insoluble material, which showed a disappearance of the nitrile and methylacrylate peaks.

Journal Article↗
PubMed1979

Isolation and identification of 3,3',5,5'-tetrabis(tert-butyl)stilbenequinone from polyethylene closures containing titanium dioxide and butylated hydroxytoluene.

A yellow compound was isolated from commercially available, discolored, polyethylene ophthalmic closures containing titanium dioxide and butylated hydroxytoluene (I). This compound was present at 7.46 ppm (w/w). It was identified by UV, IR, and mass spectra as 3,3',5,5'-tetrabis(tert-butyl)stilbenequinone (II), a dimer of I. Further structural confirmation was obtained by NMR. Formation of II is catalyzed by titanium dioxide.

Butylated Hydroxytoluene↗
PubMed1977

Chemical modificiation of collagen and the effects on enzyme-binding: mechanistic considerations.

The effect of structural modification on the enzyme-binding capacity of collagen has been studied using beta-galactosidase (E. coli K12) immobilized to collagen membrane by the impregnation procedure. The apparent steady-state activities of the resultant collagen-enzyme complexes were determined as a means of evaluating the enzyme-binding capacity of the modified collagen. In addition, the amount of enzymic protein bound to the collagen support was determined by the tryptophan content of the complex. The tertiary structure of the collage matrix was modified by cross-linking with the difunctional reagent, glutaraldehyde, and by aging in the dry state. Such structural modifications were found to markedly reduce the enzyme (beta-galactosidase) binding capacity of collagen films. The enzyme-binding capacity of the crosslinked collagen membrane was completely restored by proteolytic enzyme treatment of the aged film but only partly so for the glutaraldehyde treated films. Proteolytic enzymes used to treat a dispersion of collagen microfibrils prior to casting into a membrane also resulted in an increase in enzyme-binding. The effect of structural modification of collagen on enzyme-binding and the locus of enzyme attachment are discussed.

Animals↗