PubMed Health⌕ Search

Biomedical subjects

J R Bailey

Publications and source records attributed to J R Bailey.

At least 37 records · Page 2Linked to original sources
PubMed1992

Myoglobin supported oxygen consumption in isolated rat hearts under dysoxic conditions.

Oxygen consumption was assessed in contracting, isolated rat hearts subjected to Langendorff perfusion. Initially, hearts were perfused with Krebs-Henseleit bicarbonate medium (KHB). Some hearts were treated with a 10 min pulse of medium containing 0.05 mM phenylhydrazine to oxidize approximately 78% of myoglobin to a state incapable of binding oxygen. Stepwise reduction in input PO2 resulted in a decline in oxygen consumption (MO2) in control and treated hearts. Phenylhydrazine treatment had no effect upon MO2 in hearts perfused with medium having a PO2 of about 585 mmHg or higher. However, at an input PO2 of approximately 370 mmHg, MO2 was decreased to 60% of the level at an input PO2 of 710 mmHg in untreated hearts and significantly lower to 32% of initial level in myoglobin blocked hearts. In subsequent experiments, hearts were perfused with KHB containing human red blood cells (RBCs) to elevate the oxygen content of the perfusate. The addition of RBCs to medium having a PO2 of approximately 140 mmHg resulted in enhancement of MO2 and maintenance of performance. But the preparations were considered to be dysoxic since MO2 with RBCs in the medium (PO2 approximately 140 mmHg) was lower than under perfusion with KHB (PO2 approximately 710 mmHg). This should however not detract from the utility of the model in elucidating myoglobin function under oxygen limiting conditions. At an input PO2 of 140 mmHg hearts treated with phenylhydrazine to impede myoglobin function had a significantly lower MO2 and viability than untreated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Quantitative plasma disposition of retinol and retinyl esters after high-dose oral vitamin A administration in the cynomolgus monkey.

A solid-phase extraction technique followed by automated high-performance liquid chromatography sample elution was successfully used to evaluate the effect of three pharmaceutical parameters on the plasma profile of various forms of vitamin A after an oral dose to cynomolgus monkeys. The three parameters evaluated were the chemical form of vitamin A (retinol versus retinyl acetate), the vehicle (acetone/Tween 20/water versus acetone/soybean oil), and the retinol dose (2, 10, and 50 x 10(3) retinol equivalents/kg). The form of the administered compound, retinol or retinyl acetate, appeared to have no major effect on the formation of nonpolar retinoids. The ester profile in plasma differed depending on whether the dose was administered in the water-based or the oil-based vehicle. Irrespective of the vehicle type the predominant retinoid formed was retinyl palmitate/oleate. However, retinol doses in the water-based vehicle formed relatively high concentrations of retinyl laurate and retinyl myristate but no retinyl linolenate. The retinol dose in the oil-based vehicle formed consistent, but relatively minor, concentrations of retinyl linolenate, higher relative concentrations of retinyl linoleate, and no retinyl laurate or myristate. The dose of retinol administered had an impact on the diversity of the nonpolar retinoid profile. The low dose led to the presence of almost exclusively retinyl palmitate/oleate and retinyl stearate, whereas at higher doses the other retinyl esters became major retinol constituents.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

No increase in carcinogen-DNA adducts in the lungs of monkeys exposed chronically to marijuana smoke.

Rhesus monkeys exposed to marijuana smoke either 7 or 2 days/weeks (HI and LO groups, respectively), or ethanol-extracted marijuana smoke for 7 days/week (EM) or sham treatment (SH) for 1 year were sacrificed 7 months following the last exposure. Pulmonary levels of carcinogen-DNA adducts were determined. Although mean or median adduct levels were not statistically different, 15 of 22 adduct measures were highest in the EM group and lowest 12 of 22 times in the SH group. The levels of aromatic carcinogen-DNA adducts seem no higher in the lungs of animals exposed to marijuana smoke than in untreated animals. Ethanol-extracted marijuana may have effects greater than marijuana itself.

Animals↗
PubMed1992

Ciprofloxacin-induced acute interstitial nephritis.

Acute renal failure is a complication attributed to numerous medications. Few cases linked to the newer fluoroquinolones have been described. We report a case of acute interstitial nephritis confirmed by renal biopsy that developed in a patient within days of starting ciprofloxacin therapy. A review of the literature reveals common clinical manifestations of this rare adverse effect. Clinicians should be aware of this potential complication of ciprofloxacin use.

Acute Kidney Injury↗
PubMed1992

Chronic marijuana smoke exposure in the rhesus monkey. II: Effects on progressive ratio and conditioned position responding.

Sixty-two male rhesus monkeys were trained to respond in an operant test battery that included tasks thought to allow measurement of aspects of motivation and color and position discrimination. Subjects were assigned to eight treatment groups (n = 7-8) based upon behavioral performance. There were two behavioral groups: ACTIVE = behavior assessed throughout the 365 days of active exposure and beyond, and RESIDUAL = behavior assessed beginning 2 months after the last exposure. Each behavioral group had four dose groups: HI = smoke from one marijuana (MJ) cigarette/day 7 days/week; LO = MJ smoke only on weekends; EX = smoke from one extracted MJ (placebo) cigarette/day 7 days/week; SH = sham exposure 7 days/week. For the motivation task, both HI and LO ACTIVE groups earned significantly fewer reinforcers than did both ACTIVE control groups during the last several months of exposure. These effects disappeared within 2 to 3 months of cessation of treatment, and no similar effect was present when RESIDUAL groups were tested. Performance of the color and position discrimination task was adversely affected in one of eight HI ACTIVE subjects throughout most of the chronic exposure, and there was a trend toward residual deficits in performance of this task in the HI RESIDUAL group compared to both SH and EX RESIDUAL controls. These data could be interpreted to mean that during periods of chronic use, MJ produces an amotivational-like syndrome in rhesus monkeys and that this syndrome disappears only several weeks to months after the last exposure.

Animals↗
PubMed1991

Frequency of urination and its effects on metabolism, pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in beagle dogs given the carcinogen 4-aminobiphenyl.

The human urinary bladder carcinogen, 4-aminobiphenyl (ABP), is known to undergo hepatic metabolism to an N-hydroxy arylamine and its corresponding N-glucuronide. It has been proposed that these metabolites are both transported through the blood via renal filtration to the urinary bladder lumen where acidic pH can facilitate the hydrolysis of the N-glucuronide and enhance the conversion of N-hydroxy-4-aminobiphenyl (N-OH-ABP) to a reactive electrophile that will form covalent adducts with urothelial DNA. Blood ABP-hemoglobin adducts, which have been used to monitor human exposure to ABP, are believed to be formed by reactions within the erythrocyte involving N-OH-ABP that has entered the circulation from the liver or from reabsorption across the urothelium. To test these hypotheses directly, experimental data were obtained from female beagles given [3H]ABP (p.o., i.v., or intraurethrally). [3H]N-OH-ABP (i.v. or intraurethrally), or [3H]N-OH-ABP N-glucuronide (i.v.). Analyses included determinations of total ABP in whole blood and plasma, ABP-hemoglobin adducts in blood erythrocytes, ABP and N-OH-ABP levels (free and N-glucuronide) in urine, urine pH, frequency of urination (controlled by urethral catheter), rates of reabsorption of ABP and N-OH-ABP across the urothelium, and apparent volumes of distribution in the blood/tissue compartment. The major ABP-DNA adduct, N-(guan-8-yl)-4-aminobiphenyl, was also measured in urothelial and liver DNA using a sensitive immunochemical method. An analog/digital hybrid computer was then utilized to construct a multicompartmental pharmacokinetic model for ABP and its metabolites that separates: (a) absorption; (b) hepatic metabolism and distribution in blood and tissues; (c) ABP-hemoglobin adduct formation; (d) hydrolysis and reabsorption in the urinary bladder lumen; and (e) excretion. Using this model, cumulative exposure of the urothelium to free N-OH-ABP was simulated from the experimental data and used to predict ABP-DNA adduct formation in the urothelium. The results indicated that exposure to N-OH-ABP and subsequent ABP-DNA adduct formation are directly dependent on voiding frequency and to a lesser extent on urine pH. This was primarily due to the finding that, after p.o. dosing of ABP to dogs, the major portion of the total N-OH-ABP entering the bladder lumen was free N-OH-ABP (0.7% of the dose), with much lower amounts as the acid-labile N-glucuronide (0.3% of the dose).(ABSTRACT TRUNCATED AT 400 WORDS)

Aminobiphenyl Compounds↗
PubMed1991

Influence of dose and pharmaceutical formulation of vitamin A on plasma levels of retinyl esters and retinol and metabolic generation of retinoic acid compounds and beta-glucuronides in the cynomolgus monkey.

Retinoid concentrations were analyzed in plasma of nonpregnant female cynomolgus monkeys after oral administration of retinol or retinyl acetate at doses of 2, 10, or 50 mg (as retinol) per kilogram body weight dissolved in acetone/soybean oil (1/9) or acetone/Tween 20/water (1/5/4). All-trans-retinoic acid, 13-cis-retinoic acid, all-trans-4-oxoretinoic acid, and 13-cis-4-oxoretinoic acid as well as the conjugates of retinol and all-trans-retinoic acid with beta-D-glucuronic acid represented major polar plasma retinoids after high doses of vitamin A. The relative bioavailability of vitamin A as well as the biotransformation to more polar retinoids was independent of the molecular form of vitamin A (retinol or retinyl acetate) used for dosing. After administration of 2 mg/kg and, in particular, after a 10 mg/kg dose, the metabolic formation of polar retinoids in plasma was much more extensive with the detergent-based vehicle compared to the oil-based vehicle. At 50 mg/kg, comparable metabolism was observed for both forms. Polar metabolites of retinol were increased in a more than linear fashion with the detergent-based vitamin A preparations between 2 and 10 mg/kg and with the oil-based preparations between 10 and 50 mg/kg. Since retinoic acid compounds have previously been shown to be potent teratogens in various animal species and humans, their metabolic formation may be of significance for the teratogenic activity of high doses of vitamin A. In addition to the dose, the pharmaceutical preparation of vitamin A could therefore be a major determinant of the developmental toxicity of vitamin A.

Animals↗
PubMed1991

Marijuana exposure and pulmonary alterations in primates.

As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

Animals↗
PubMed1991

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Chronic marijuana smoke exposure in the rhesus monkey. I. Plasma cannabinoid and blood carboxyhemoglobin concentrations and clinical chemistry parameters.

This report is the first in a series about a large multidisciplinary study designed to determine whether chronic marijuana (MJ) smoke exposure results in residual behavioral and/or neuropathological alterations in the rhesus monkey. Prior to the initiation of a year of chronic MJ smoke exposure, 64 periadolescent male rhesus monkeys were trained for 1 year to perform five operant behavioral tasks and then divided, according to their performance in these tasks, into four exposure groups (n = 15-16/group): (1) a high dose (HI) group, exposed 7 days/week to the smoke of one standard MJ cigarette; (2) a low dose (LO) group, exposed on weekend days only to the smoke of a standard MJ cigarette; (3) an extracted MJ cigarette (EX) group, exposed 7 days/week to the smoke of one ethanol-extracted MJ cigarette; and (4) a sham group (SH), exposed 7 days/week to sham exposure conditions. Daily exposures for 1 year were accomplished using a mask that covered the subjects' nose and mouth. Average body weights (initially 3.7 +/- 0.5 kg, mean +/- SD) and rates of weight gain (approximately 0.1 kg/month) were the same for all groups throughout the entire experiment. During the first week of exposure, plasma concentrations of delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-THC in the HI group were 59 +/- 7 (mean +/- SE) and 5.5 +/- 1.5 ng/ml, respectively, 45 min after MJ smoke administration and did not change significantly at similar times after exposure throughout the remainder of the year. Whole blood carboxyhemoglobin levels increased to approximately 13% 1 min after exposure to smoke in either the MJ or the EX groups. Comparison of blood chemistry and hematology values before, during, and after exposure indicated no differences for most parameters. During exposure, lymphocytes, alkaline phosphatase and gamma-glutamyl transferase were depressed in the HI group compared to in the SH group. During exposure, aspartate aminotransferase was elevated for both the HI and EX groups, suggesting a general effect of smoke exposure. Because these effects were transient and remained within the range of reported normal values, these data indicate that long-term, experimental exposure to MJ smoke is feasible and does not compromise the general health of the rhesus monkey.

Alkaline Phosphatase↗
PubMed1991

Transplacental passage of a human relaxin administered to rhesus monkeys.

A synthetic version of the human relaxin encoded by the human gene 2 (hR1x-2) was administered to pregnant rhesus monkeys (Macaca mulatta) on gestational days 141-158. Monkeys (three per group) received doses of 100 micrograms/kg or 2000 micrograms/kg as a continuous i.v. infusion over 2 h into a radial vein. One monkey in the low-dose group received, along with the unlabelled hR1x-2, 25.5 microCi/kg of the test material internally labelled with [35S]cysteine. Immunoreactive hR1x-2, as measured by enzyme-linked immunosorbent assay, appeared in all fetuses within 30 min (the first sampling time) of beginning the infusions. Peak fetal plasma levels of hR1x-2 were only 0.8-1.5% of the maternal values. Only 8-15% of the fetal serum radioactivity was hR1x-2. Radioactivity from maternal urine pooled over the 4-h experiment did not elute at the volume corresponding to hR1x-2, but near the column volume.

Animals↗
PubMed1990

Oxygen uptake by isolated perfused fish hearts with differing myoglobin concentrations under hypoxic conditions.

Hearts from three species of fish with varying myoglobin content were perfused with stepwise changes in input perfusate PO2 from approximately 160 to 10 mmHg. Flow through the heart, rate of contraction, and afterload were kept constant. This standardized stroke volume and bulk flow of perfusate to the myocytes since these hearts are nourished by the fluid in the ventricular lumen. In some cases NaNO2 was added to the perfusion medium to decrease existing levels of functional myoglobin. Myoglobin-rich hearts were able to extract a constant amount of oxygen until perfusate PO2 had fallen below 80 mmHg. At this point oxygen uptake began to decline. These hearts consumed oxygen until input PO2 was 10 mmHg or less. When normoxic conditions were restored the myoglobin-rich hearts showed complete recovery. Performance was maintained at a constant level over the entire range of input PO2. Myoglobin-poor hearts and nitrite-treated hearts were unable to sustain constant levels of oxygen consumption in the face of a declining perfusate PO2. These hearts were unable to extract oxygen from the medium and failed at perfusate PO2's of 40 mmHg for naturally myoglobin-poor hearts and 30 mmHg for nitrite-treated hearts. Half-maximal oxygen consumptions were attained by myoglobin-rich hearts at lower input PO2's than either myoglobin-poor or nitrite-treated hearts. The impact of myoglobin in intact heart is apparent at relatively high extracellular PO2's (40-80 mmHg) in this model system.

Animals↗
PubMed1989

Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys.

The acute behavioral effects of marijuana smoke were assessed in rhesus monkeys using a battery of food-reinforced complex operant tasks that included incremental repeated acquisition (IRA, n = 9), conditioned position responding (CPR, n = 8), progressive ratio (PR, n = 8), delayed matching to sample (DMTS, n = 6), and temporal response differentiation responding (TRD, n = 3). Marijuana or placebo smoke was delivered by a specialized face mask 15-min before sessions at exposure levels of 1, 5, 10, and 15 puffs (35cc/puff) or one cigarette smoked to a butt length of approximately 10 mm (approximately 20 puffs). Marijuana smoke caused significant disruptions of performance in all tests except PR after exposure to 10 or more puffs. Generally, response rates decreased or latencies to respond increased. Performance in the PR test was not consistently affected by marijuana exposure. Accuracy of responding was not altered by marijuana smoke at doses lower than those that decreased response rates in the IRA or CPR tests. In the three animals performing under all five schedules, the relative sensitivities for detecting marijuana behavioral effects were DMTS = TRD greater than IRA = CPR greater than PR. These results suggest that performance under operant schedules that are thought to represent some aspect of time perception, short-term memory, learning, motivation, and position discrimination show differential sensitivity to disruption by marijuana smoke, a finding similar to that noted previously for iv THC administration.

Animals↗
PubMed1989

Pharmacokinetics of doxylamine, a component of Bendectin, in the rhesus monkey.

The elimination of doxylamine and metabolites was determined after iv administration of [14C]doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly increased and the polar doxylamine metabolites were significantly decreased as the iv doxylamine succinate dose was increased. The plasma elimination of gas chromatograph (GC)-detected doxylamine was determined after oral administration of Bendectin (doxylamine succinate and pyridoxine hydrochloride) at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose increased, the clearance of doxylamine decreased. A statistically evaluated fit of the oral data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data.

Animals↗
PubMed1989

Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.

MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

3,4-Methylenedioxyamphetamine↗
PubMed1988

Neurochemical and neurohistological alterations in the rat and monkey produced by orally administered methylenedioxymethamphetamine (MDMA).

MDMA is an amphetamine analog prescribed by some health professionals in the field of psychotherapy and used as a recreational drug by the general public. In recent reports, investigators have suggested that MDMA produces acute neurotoxicity when administered by subcutaneous injection. In order to determine if MDMA produces lasting neurochemical alterations after oral administration, groups of six rats (adult male Sprague-Dawley) were dosed by gavage with either 40 or 80 mg/kg of MDMA or saline vehicle once every 12 hr for 4 days. These rats were terminated 2 weeks after the first dose along with an additional group of rats (80 mg/kg) terminated 4 weeks after the first dose. Brain regions including the hippocampus (H), caudate nucleus (CN), hypothalamus (HY), frontal cortex (FC), and brain stem (BS) were analyzed by HPLC with electrochemical detection for concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE). In the CN, 40 mg/kg MDMA produced no change in DA, DOPAC, or HVA, but a 50-60% decrease in 5-HT and 5-HIAA concentrations was observed at 2 weeks. Similar effects were observed at 80 mg/kg at both 2 weeks and 4 weeks. A temporary decrease was also seen in DA (21%) and in HVA (34%) 2 weeks but not 4 weeks after the 80 mg/kg dose regimen. In the H, MDMA (40 or 80 mg/kg) produced no change in NE, but a 50-60% decrease was seen in 5-HT and 5-HIAA concentrations at 2 weeks. Concentrations of 5-HT and 5-HIAA were significantly decreased in the HY and FC by all MDMA treatments, but DA and DOPAC concentrations were not altered as compared to vehicle controls. BS was least affected by treatment with no change in DA, DOPAC, or 5-HIAA concentrations and only a slight decrease in 5-HT (19-33%) concentrations at 2 weeks but not at 4 weeks. To determine the sensitivity of the nonhuman primate to MDMA, a total of nine rhesus monkeys were dosed with vehicle or 5 or 10 mg/kg MDMA (n = 3) by gastric intubation twice per day for 4 days. One month after MDMA dosing, a dose-related reduction from vehicle control values for 5-HT and 5-HIAA was observed. These results indicate that the monkey may be more sensitive than the rat to the persistent serotonergic neurotoxicity of MDMA.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Methylenedioxyamphetamine↗