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Biomedical subjects

C N Smith

Publications and source records attributed to C N Smith.

At least 19 recordsLinked to original sources

Macrocytic-megaloblastic anemia in male NIH Swiss mice following repeated exposure to 1,3-butadiene.

Thymic lymphoma/leukemia is the major cause of death in B6C3F1 mice chronically exposed to 1,3-butadiene (BD). Similar to radiation-induced murine thymic lymphoma, the bone marrow is also a major target organ. Because of the association of murine thymic lymphoma with endogenous type-C murine leukemia retroviruses (MuLV) present in the germ line of most strains of laboratory mice, including B6C3F1 and its parent strains, we examined the effects of BD exposure on NIH Swiss mice which do not possess intact endogenous ecotropic MuLV. Male NIH Swiss mice exhibited a macrocytic-megaloblastic anemia following inhalation of 1250 ppm BD for 6 weeks. Treatment-related changes included decreases in circulating erythrocytes, total hemoglobin, and hematocrit and an increase in mean corpuscular volume. An eightfold increase in circulating micronuclei was also observed. The anemia was not accompanied by a significant alteration in mean corpuscular hemoglobin concentration, an increase in circulating reticulocytes, or an increase in circulating nucleated erythrocytes. These findings are consistent with a treatment-related macrocytic-megaloblastic anemia and indicate that the bone marrow is an important target for BD toxicity in mice independent of MuLV background and expression.

Anemia, Macrocytic

Macrocytic-megaloblastic anemia in male B6C3F1 mice following chronic exposure to 1,3-butadiene.

In the present study exposure to 1,3-butadiene (BD) resulted in a macrocytic-megaloblastic anemia in male B6C3F1 mice following chronic inhalation of 1250 ppm for 6 to 24 weeks. Treatment-related changes evident after 6 weeks of exposure included a decrease in circulating erythrocytes, total hemoglobin, and hematocrit and an increase in mean corpuscular volume. A leukopenia, due primarily to a decrease in segmented neutrophils, and a five- to sixfold increase in circulating micronuclei were observed after 6 and 24 weeks of exposure. These changes were not accompanied by a significant alteration in mean corpuscular hemoglobin concentration, an increase in circulating reticulocytes, or circulating nucleated erythrocytes. A consistent treatment-related alteration in bone marrow cellularity was not found. However, flow cytofluorometric analysis of bone marrow DNA cell cycle kinetics revealed a 44% increase in proliferative index relative to controls, due primarily to an increase in the proportion of cells in S phase. These findings are consistent with a treatment-related macrocytic-megaloblastic anemia and indicate the bone marrow to be an important target organ for BD toxicity.

Anemia, Macrocytic

Effect of sampling site and collection method on variations in baseline clinical pathology parameters in Fischer-344 rats. II. Clinical hematology.

An analysis of the influence of blood-sampling site and collection method on peripheral hematology parameters was conducted in age-matched male Fischer-344 rats. Sites examined for blood collection were the right ventricle, abdominal aorta, abdominal vena cava, retroorbital plexus, and tail. Collection methods used included syringe (10 ml), Vacutainer(s) (3 ml or 3 ml X 2), and capillary tube. Blood collected from the tail exhibited leukocyte counts approximately twice those of samples samples from other sites. Blood collected from the retroorbital plexus and tail exhibited significant variations in white blood cell count, red blood cell count, hemoglobin, and hematocrit, and differences in leukocyte differential counts of lymphocytes and neutrophils when compared with other sites. Blood collected from the abdominal aorta and in a second Vacutainer from the right ventricle exhibited lower erythrocyte, leukocyte, and platelet counts than that collected from other sites with the exception of the platelet count from tail blood which was lower than that from all other sites. Although parameter values vary with sample site selection, those obtained from right ventricle blood were the least variable and the most consistent when compared with all other methods.

Animals

Effect of sampling site and collection method on variations in baseline clinical pathology parameters in Fischer-344 rats. 1. Clinical chemistry.

An analysis of the influence of blood sampling site and collection method on clinical chemistry parameters was conducted in male Fischer-344 rats. Sampling sites compared included the right ventricle, aorta, vena cava, retroorbital sinus, and tail. Methods of collection included Vacutainer (3 ml sample), syringe (exsanguination), and capillary tube. Nineteen frequently measured clinical chemistry procedures were determined, including serum enzymes, cholesterol, and triglycerides. Significant differences were noted for almost every parameter as a function of sampling site. Samples collected from the right ventricle with a Vacutainer produced the most representative results for most but not all procedures when compared to the overall mean (for all methods). The largest differences were encountered in samples obtained from tail and retroorbital plexus. Exanguination also resulted in significant differences for some parameters when compared to smaller sample volumes obtained from the same site. It was concluded that sampling site and collection method can be a major source of variation in clinical chemistry measurements, and in selection of an appropriate method, one should consider which parameters are likely to be of major interest.

Animals

Theophylline elimination in the pregnant and fetal rabbit.

Aminophylline and theophylline are commonly used to treat asthma. We studied theophylline pharmacokinetics in the pregnant and nonpregnant rabbit as well as in the intrauterine and extrauterine fetus. The t1/2 was increased (p less than 0.05) and the clearance was decreased (p less than 0.05) in the pregnant compared to the nonpregnant rabbit. The t1/2 of theophylline in the newborn rabbit was 43.5 +/- 12.0 hr, approximately 15 times longer than in the nonpregnant rabbit. Twenty-four hours after a 20 min maternal aminophylline infusion, both the intrauterine fetus and maternal serum theophylline concentrations were very similar. The transplacental transfer from the maternal to fetal circulation occurred in less than 1 hr. The maternal to fetal serum ratios for theophylline were similar after a 5-day maternal aminophylline infusion (ratio 1.22 +/- 0.20) or after a 20 min infusion (ratio 1.24 +/- 0.20). Our findings indicate that the newborn rabbit eliminates theophylline very slowly, and maternal aminophylline or theophylline therapy that would result in high peak serum concentrations in the fetus, particularly just before birth, should be avoided.

Aminophylline

The persistence and disappearance by washoff and dryfall of methoxychlor from soybean foliage--a preliminary study.

The persistence and disappearance (washoff or dryfall) of methoxychlor [2,2-bis(p-methoxyphenyl)-1,1,1-trichloroethane] from mature soybean [Glycine max (L.) Merrill] foliage was investigated in a small field plot study under natural rainfall conditions in 1977 and 1978. Residue analyses were conducted using whole plant samples. Methoxychlor washoff rate was 8+/- 4% of the amount on plants (prior to rain) per centimeter of rainfall, regardless of time after application. Total seasonal washoff for 1978 accounted for 33.5% of the applied pesticide; however, 30.5% of the total loss was removed by washoff on the second day after application. Dryfall or dislodgeable residue accounted for less than 1% of the amount applied. The amount of dryfall was significantly greater in plots entered by workers than in those where entry was avoided. More than 19% of the applied methoxychlor was lost as a result of through-fall to the ground during application to the plots. Statistical analyses indicated that within-sample variation for mechanical chopping of plant samples was significantly smaller at the 5% level than for a hand chopping method. Results from this study will be useful in defining research objectives for the development of algorithms to describe the behavior of foliar-applied compounds. Such algorithms are necessary for estimating runoff losses of insecticides to water bodies.

Methoxychlor

Endotoxin clearance after intralipid infusion.

Healthy 6-8-wk-old New Zealand white rabbits were injected with chromium-chloride- or sodium-chromate-labeled E. coli endotoxin after rapid infusion (10 ml/kg in 1 hr) or slow and repeated infusions (40 ml/kg daily for 7 consecutive days) of 10% Intralipid. Endotoxin clearance rates and RES organ uptakes were determined and the results were compared with those of the controls treated with correspondingly equal volumes of 5% D/W instead of fat. In the acute experiment, the clearance rates were similar in all animals during the first 15 min following endotoxin injection. After this phase, however, experimental animals had faster endotoxin clearance and eventually higher organ uptakes than the controls. In the chronic experiment, there was no significant difference in endotoxin clearance rates or total and per-gram organ uptakes between experimental and corresponding control animals infused with 5% D/W instead of fat. Experimental animals, particularly those having received multiple infusions of fat emulsion, showed deposition of polarizable brown pigment inside and outside the reticuloendothelial cells in the liver, spleen, and bone marrow. None of the controls had these pigments in their organs.

Animals

Genetic control of insects of public health importance.

During recent years many advances have been made in the development of insect control by genetic manipulation. These methods include the sterile-male technique, now well known, which depends on ionizing radiation or chemosterilization. The recent field experiment carried out by WHO in Rangoon, Burma, on Culex fatigans has demonstrated that naturally occurring cytogenetic mechanisms such as cytoplasmic incompatibility can be used successfully without the use of radiations or chemosterilants. The paper not only describes the experiment on Culex fatigans but also discusses basic concepts and theoretical considerations involved in genetic control of insects of public health importance. The possibility of using genetic mechanisms for the control of other vector species is also discussed. There are a number of problems which require study before genetic control can be used on an operational scale. These problems and suggestions for future research in this field are also outlined.

Animals