bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurements of cardiopulmonary response in awake rats during acute exposure to nearambient concentrations of ozone
Authors: Tepper Jeffrey S. , Wiester Mildred J. , Weber Mary F. , Ménache Margaret G. 
Published: October 2006

AbstractCardiopulmonary responses during acute exposure to near‐ambient (< 1.0 ppm) concentrations of ozone (O3) have not been reported for the unanesthetized rat. Such data on species sensitivity are crucial for the extrapolation of animal data to man. Therefore, this study was conducted to obtain functional measurements on awake rats using head‐out plethysmographs and intrapleural or carotid artery catheters during a 135‐min exposure to 0.0, 0.12, 0.25, 0.5 or 1.0 ppm O3. Carbon dioxide was added during alternate 15‐min periods of the exposure to increase ventilation, much like the use of exercise in human O3 exposure studies. The results established that frequency of breathing was increased and tidal volume was decreased as a function of both the concentration and the duration of exposure. Breathing mechanics and cardiopulmonary measures were only marginally affected. Differences in the response of individual rats revealed that as O3 concentration increased, the proportion of rats responding and the magnitude of the response was increased. These data indicate that, for similar functional responses, the rat's sensitivity to O3 is comparable to that observed in man.
Cardioteratogenic dose of ethanol in the chick embryo results in egg white concentrations comparable to human blood alcohol levels
Authors: Bruyere Harold J. , Kapil Ram P. 
Published: October 2006

AbstractThree‐day‐old chick embryos were exposed to a dose of ethyl alcohol (0.32 ml of 50% ethanol) that we previously demonstrated produces cardiac malformations in 96.6% of the animals. Ethanol was administered into the air sac at 72–80 h of incubation. Samples of egg white were drawn at 2, 6 and 24 h after treatment and analyzed by capillary gas–liquid chromatography. Ethanol concentrations were significantly higher at 6 and 24 h after exposure than at 2 h (P < 0.01), but there were no differences in mean concentrations between 6 and 24 h (P > 0.2). Furthermore, concentrations (43–303 mg dl−1) were comparable to human blood alcohol levels during intoxication. These results suggest that the cardioteratogenic doses of ethanol administered to chick embryos in a previous study are not excessive in terms of potential human embryo exposure.
Acetylation of 5‐aminosalicylate by hamster colon arylamine N‐acetyltransferase
Authors: Tucker Mark A. , Smith Timothy J. 
Published: October 2006

AbstractRecent evidence suggests that 5‐aminosalicylate acts as an anti‐inflammatory agent by virtue of its ability to act as a free‐radical scavenger. The major metabolite, N‐acetyl‐5‐aminosalicylate is not an effective free‐radical scavenger. We have demonstrated that an arylamine N‐acetyltransferase from hamster colon can directly acetylate 5‐aminosalicylate, suggesting that the colon may have the ability to modulate the activity of this agent through metabolic inactivation.
Differential mutagenicity of two dihydrophenalene congeners: Examination of formaldehyde generation and reactive intermediate formation as possible mechanisms
Authors: Petry T. W. , Jolly R. A. , Aaron C. S. , Schwende F. J. 
Published: October 2006

AbstractCompounds in the dihydrophenalene series are currently under investigation as potential antipsychotic agents. The mutagenicity of two compounds in this series was evaluated in several strains in the Ames Salmonella assay with and without S9 activation. U‐65,556A (2,3‐dihydro‐N,N‐dimethyl‐1H‐phenalen‐2‐amine HCI) was less mutagenic than its monomethyl analogue, U‐64,273A. Two hypotheses—the release of formaldehyde and the formation of macromolecular reactive intermediates—were evaluated as possible mechanisms for the observed mutagenicity. Formaldehyde release during biotransformation of U‐65,556A but not U‐64,273 was demonstrated, as measured by trapping with the Nash reagent. Thus, formaldehyde release does not correlate with the mutagenic potency of these compounds. Covalent binding of U‐65,556A‐[3H] equivalents to rat hepatic protein was observed, but binding to DNA, which is considered the more critical target molecule, was not observed. These data suggest that reactive intermediate formation does not explain the mutagenicity of U‐65,556A in the Ames Salmonella assay. Follow‐up studies were conducted to assess the possible contribution of tritium exchange to the observed covalent binding to protein by quantitatively recovering 3H2O from incubations containing U‐65,556A‐[3H] and rat liver microsomes. Data indicate that enzyme‐dependent formation of 3H2O does occur but that this phenomenon does not account for U‐65,556A‐[3H]‐derived, proteinbound tritium in covalent binding studies.
Toxicity of 2‐methyl‐5,6‐cyclopentapyrimidine (MCPP)
Authors: Kennedy Gerald L. 
Published: October 2006

Abstract2‐Methyl‐5,6‐cyclopentapyrimidine (MCPP, CAS No. 36274–29–0) is a white dusty solid with a powerful lingering odor and is formed as a by‐product in the polymer synthesis of an experimental polymer. The acute toxicity following both oral and inhalation exposures and the effects of repeated inhalation exposures in rats were determined. Mutagenic activity was assessed using Salmonella as the indicator organism. The chemical is moderately toxic, with the lethal dose following a single oral administration being 90 mg kg−1. Doses ≧ 130 mg kg−1 produced strong convulsions. Excessive salivation, hyperactivity and twitching were seen at 90 mg kg−1 and only mild initial weight loss was seen in surviving rats (≦ 60 mg kg). Liver injury was produced at doses as low as 17 (but not at 12) mg kg−1. The material was highly toxic by inhalation, with the approximate lethal concentration in rats following single 4‐h exposures being 9 ppm. Convulsive‐like movements were seen at ≦ 9 ppm (not at 2 ppm). Histological findings suggest that MCPP causes dilation of blood vessels with hyperemia of various organs apparent in rats exposed to 1 ppm and sacrificed 1 or 2 days post‐exposure. No evidence of liver or central nervous system damage was seen. Repeated (nine daily 4‐h exposures) inhalation of 2 ppm MCPP failed to produce any signs of a toxic response. No mutagenic activity was seen. The material needs to be considered as a potent acute toxin.
Calcium antagonists can be classified using in vitro toxicity and potency indices
Authors: Shrivastava Ravi , John Gareth , Massingham Roy 
Published: October 2006

AbstractThe toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage‐operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.
The Ca2+‐transport‐atpase of human erythrocytes as an in vitro toxicity test system—acute effects of some chlorinated compounds
Authors: Janik F. , Wolf H. U. 
Published: October 2006

AbstractInvestigations to determine the inhibitory activity on the Ca2+‐transport‐ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4‐chlorophenol. 2,4‐dichlorophenol, 2,6‐dichlorophenol, 3,4‐dichlorophcnol, 2,3,4‐trichlorophenol, 2,3,4,5‐tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)‐camphene, toxaphene, dichlorodiphenyltrichloroethane (UDT), lindane, endrin, dieldrin, α‐endosulfan, β‐endosulfan, paraquat, diallate, 2,4‐dichlorophenoxyaceticacid (2,4‐D) and 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T).Some of the compounds investigated display an inhibitory effect on the Ca2+‐transport‐ATPase at very low concentrations. The in vitro results obtained in this enzyme assay can be correlated directly with the results of other in vitro assays and with the results of in vivo investigations in different species in whkh an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca2+‐transport‐ATPase indicates a toxic effect of these compounds to cell functions.Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the cellular toxicity of various compounds.
Haematological and hepatotoxic effects of silken styles of corn in albino rats
Authors: Garg D. K. , Goyal R. N. 
Published: October 2006

AbstractThe alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maize Linn.) at 50, 100 and 150 mg kg−1 daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses.The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maize Linn.) are not significantly toxic at low and medium doses (50 and 100 mg kg−1).
Effects of 3‐methylcholanthrene or diethyl maleate on the hepatotoxicity of acetaminophen
Authors: Szymańska J. A. , Swietlicka E. A. , Piotrowski J. K. , Skrzypińska‐Gawrysiak M. , Sporny S. 
Published: October 2006

AbstractThis report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg−1 with or without pretreatment with 3‐methylcholanthrene (3MCh) or diethyl maleate (DEM).The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione.Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidation.
The pathological effects of glove and condom dusting powders
Authors: Kang N. , Griffin D. , Ellis H. 
Published: October 2006

AbstractDusting powders are used on latex gloves and condoms. They help to release these products from their moulds during manufacture and facilitate processing and donning. Dusting powders are also used on contraceptive diaphragms, sanitary napkins and in toiletries. There are numerous dusting powders in current use around the world. At present a consensus exists about the best dusting powder to use on surgical gloves, based on data about the safety of these agents in humans, as well as their manufacturing qualities. No such consensus exists for the use of dusting powders in other situations. However, there is uncertainty about whether dusting powders used in situations other than on surgical gloves are responsible for harmful effects. This study uses intraperitoneal injections in rats to examine the pathological effects of dusting powders that are in current use on surgical gloves and condoms. We suggest that dusting powders may be a source of morbidity when used in situations other than on surgical gloves and confirm the findings of previous investigators that the dusting powders we tested differ in their ability to produce pathological effects.
Spontaneous renal neoplasms in rats
Authors: Chandra M. , Riley M. G. I. , Johnson D. E. 
Published: October 2006

AbstractSpontaneous renal neoplasms in the rat are uncommon. This paper presents the incidence and histopathological features of various long‐term developing renal tumors observed in control rats from 17 carcinogenicity studies (1340 males and 1329 females) in Sprague‐Dawley rats and 10 carcinogenicity studies (530 males and 530 females) in Fischer‐344 (F‐344) rats. Renal cell adenoma (0.08% in Sprague‐Dawley and 0.28% in F‐344), lipoma/liposarcoma (0.37% in Sprague‐Dawley and 0.75% in F‐344) and transitional cell carcinoma (0.07% in Sprague‐Dawley and 0.09% in F‐344) were observed in both Sprague‐Dawley (0.49%) and F‐344 (1.13%) rats. Pulmonary metastasis was observed from one case of transitional cell carcinoma. Renal cell carcinoma with metastasis to the lung and liver was seen in one F‐344 rat. In addition, transitional cell papilloma and nephroblastomas were also observed in Sprague‐Dawley rats. Metastases from nephroblastoma were seen in the lungs and renal lymph node in two cases. In both rat strains, the tumor incidence was higher in males than in females.
Sensory and pulmonary irritation of aliphatic amines in mice: A structure–activity relationship study
Authors: Gagnaire F. , Azim S. , Simon P. , Cossec B. , Bonnet P. , de Ceaurriz J. 
Published: October 2006

AbstractThe expiratory bradypnea indicative of upper airway irritation in mice was evaluated during a 15‐min oronasal exposure to increasing concentrations of sixteen aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, the sixteen amines were tested for pulmonary irritation by measuring the decrease in respiratory rate of (non‐anaesthetized) tracheally cannulated mice (RD50 TC). The RD50 and RD50 TC values and their ratios were related to n‐octanol/water partition coefficients (log P). The RD50 values associated with exposure to saturated amines ranged from 17 to 300 ppm. The RD50TC values for these saturated amines ranged from 35 to 489 ppm. The RD50 and RD50TC values of saturated amines were closely related to the n‐octanol/water partition coefficient, indicating that the more lipophilic amines are more irritant for the upper and lower respiratory tracts. The RD50TC/RD50 values were much less closely related to the n‐octanol/water partition coefficient.Based on the results, tentative standards are suggested for the studied amines.
Dibromomethane and carbon monoxide in the rat: Comparison of the cardiovascular and metabolic effects
Authors: Fozo Michael S. , Penney David G. 
Published: October 2006

AbstractThe goals of this study were to examine the cardiovascular and metabolic responses to a dihalogenated methane and to compare them to inhaled CO. One group of male Sprague‐Dawley rats received an i.p. injection of either 3 or 6 mmol kg−1 dibromomethane (DBM) diluted 1:3 with sesame oil. Measurements of carboxyhemoglobin (COHb), rectal body temperature (BT), heart rate, systolic blood pressure (BP) and blood glucose and lactate concentrations were made at times 0, 30, 60, 120, 240, 360, 480, 600, 720, 840, 1020, 1440 and 1680 min. A second group of rats received only sesame oil and was tested in the same manner. A third group of rats breathed 225 ppm CO for 120 min before being tested. Peak COHb levels were 16% 8 h after 3 mmol kg−1 DBM, 18% 12h after 6 mmol kg−1 DBM and 17% in the CO‐exposed group. The sesame oil controls exhibited no elevation in COHb. The BT dropped by ca. 1°C in both the DBM‐ and CO‐exposed rats, while there was no BT change in the sesame oil controls. The BT dropped by 1.0°C and 1.2°C after 6h in the 3 and 6 mmol kg−1 DBM groups, respectively, and by 0.9°C after 120 min in the CO‐exposed group. The CO‐exposed rats displayed a 12 mmHg decrease in systolic BP, while both doses of DBM failed to produce any significant BP change. The BP in the sesame oil controls remained constant. There were no significant changes in heart rate or in blood glucose or lactate in any of the experimental groups. The lack of a BP response in the DBM rats may be due to DBM interferring with the rat's normal response to CO, or to the effects of dissolved CO vs. COHb. Dibromomethane uptake results in the development of significant and prolonged COHb saturation, at a level similar to that resulting from inhalation of 225 ppm CO. Although BT regulation is impaired, DBM appears not to have significant effects on BP, heart rate or blood glucose and lactate concentrations.
Cimetidine prevents and partially reverses CCl4‐induced liver cirrhosis
Authors: Muriel Pablo , Mera Elvia , Castillo Carlos , Mourelle Marisabel 
Published: October 2006

AbstractLiver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3·). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4‐induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg−1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, γ‐glutamyl transpeptidase (γ‐GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, γ‐GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co‐treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
Hemolysis and deformability of erythrocytes exposed to butoxyacetic acid, a metabolite of 2‐Butoxyethanol: II. Resistance in red blood cells from humans with potential susceptibility
Authors: Udden Mark M. 
Published: October 2006

Abstract2‐Butoxyethanol causes hemolysis in rodents but not in humans. 2‐Butoxyethanol‐induced hemolysis is primarily due to the effect of its metabolite 2‐butoxyacetic acid (BAA). 2‐Butoxyacetic acid did not cause hemolytic effects when incubated with blood from a limited number of normal individuals. Because 2‐butoxyethanol is contained in many consumer products, the possibility that there may be human subpopulations susceptible to hemolysis by BAA was examined. 2‐Butoxyacetic acid was incubated with red blood cells from healthy young and older individuals and with red blood cells from patients with hereditary spherocytosis and sickle cell disease. After incubation of red blood cells with or without 2.0 mM BAA for up to 4 h, conditions that readily hemolyzed rat red blood cells, there was no increase in hemolysis or changes in mean cellular volume or morphology. The deformability of erythrocytes treated with BAA was also measured using a nuclepore filtration technique. No changes in deformability due to treatment with BAA were detected. Although BAA is a potent cause of hemolysis in rats, red blood cells in humans, including the elderly and patients with two disorders marked by chronic hemolysis, were not susceptible to BAA‐induced hemolysis or loss of deformability.
Clinical effects of organophosphorus cholinesterase inhibitors
Authors: Sidell Frederick R. 
Published: October 2006

AbstractNerve agents, highly toxic organophosphorus cholinesterase inhibitors, inhibit acetylcholinesterase and cause an accumulation of acetylcholine. Clinical effects depend on the route and amount of exposure and include miosis, bronchoconstriction, excessive secretions, vomiting, seizures, and cessation of respiratory and cardiac activity. Eye effects include miosis, engorgement of ocular vessels, pain, and a decrease in light sensitivity. Therapy consists of atropine, a cholinesterase reactivator (pralidoxime), and ventilation as needed.
Evaluation of an accelerated aging medium for acrylic bone cement based on analysis of nanoindentation measurements on laboratory‐prepared and retrieved specimens
Authors: Lewis Gladius , Xu Jie , Dunne Nicholas , Daly Catherine , Orr John 
Published: October 2006

AbstractThe thrust of the study was a critical evaluation of the efficacy of a medium (30% v/v H2O2, at 60°C) that has been suggested in a literature report as being suitable for simulating the oxidative aging process, seen in vivo, in the acrylic bone cement mantles of total hip and knee joint replacements. For this purpose, quasi‐static and dynamic nanoindentation measurements were used to obtain material properties—elastic modulus, E; hardness, H; and the variation of the storage and loss moduli with the frequency of the applied indenting force—of Palacos®R acrylic bone cement specimens after various periods of immersion (7, 14, 21, and 28 days) in the aging solution, and of specimens prepared from cement mantles retrieved from cemented total hip joint replacements after various times in vivo (0.92–21 years). Also, best‐fit relationships were obtained between E and time in the H2O2 solution (t), H and t, E and in vivo time (T), and H and T. This body of results points to the possibility that the aging solution is effective, although the evidence is not conclusive. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Incorporation of 2(S)‐methylbutanoic acid‐1‐14C into the structure of mevinolin
Authors: Willard Alvin K. , Smith Robert L. 
Published: October 2006

AbstractA route to mevinolin () bearing (S)‐2‐methylbutanoic acid ‐1‐14C as the ester side chain has been developed. The structure of mevinolin () was degraded and selectively protected to provide the alcohol in three steps. Incorporation of 14C was accomplished by acylation of alcohol with (R,S)‐2‐methylbutyryl chloride‐1‐14C. Cleavage of the silyl ether protecting group in the resulting mixture of esters provided the two diastereoisomers and which were separated by reverse‐phase liquid chromatography. Mevinolin ‐ 14C () was also converted to the ammonium salt of the corresponding dihydroxy acid.