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Biomedical subjects

F W Oehme

Publications and source records attributed to F W Oehme.

At least 19 recordsLinked to original sources

Perinatal hypocuprosis affects synthesis and composition of neonatal lung collagen, elastin, and surfactant.

To investigate the role of iron, ascorbate, and fructose on copper depletion and the effect of copper depletion on neonatal lung collagen, elastin, and surfactant, female rabbits were fed a control diet [10 parts per million (ppm) copper], a basal marginal copper diet (1.5 ppm), or a basal diet containing a high concentration of iron (1,750 ppm), ascorbic acid (1%, wt/wt), or fructose (20% of carbohydrates, wt/wt) or a combination of iron, ascorbic acid, and fructose throughout gestation. Whereas 10% of neonates in the control group died in the first 24 h, 27-67% of the offspring of rabbits fed the marginal copper diet died. Birth weight was also lower for the pups of the females fed the marginal copper diets. Lungs of neonates born to females fed iron or ascorbate and marginal copper diets had low levels of copper, high proportions of acid-extractable, high-molecular-weight collagen, and low lysyl-oxidase activities, consistent with incomplete maturation of collagen. The bronchoalveolar lavage fluids of newborns whose mothers were fed marginal copper diets alone or in combination with iron and/or ascorbate had lower levels of total surfactant phospholipids than the fluids from lungs of control newborns. The lower surfactant phospholipid content of these groups could be attributed mainly to lower phosphatidylcholine and, in particular, dipalmitoylphosphatidylcholine levels. These results suggest that high maternal intakes of iron, ascorbate, or their combination in pregnancy deplete biologically available copper, which in turn induces neonatal lung abnormalities.

Animals

The effect of a single oral dose of tri-o-cresyl phosphate on neurotoxic esterase and acetylcholinesterase activities in the central nervous system, erythrocytes and plasma.

This study reports the activity of neurotoxic esterase (NTE) and acetylcholinesterase (AChE) in the blood and central nervous system (CNS) of swine 6, 12, 24 and 48 h after a single oral dose of 800 mg tri-o-cresyl phosphate (TOCP)/kg. At all evaluated intervals, inhibition of NTE activity in leukocytes and the CNS was 88% or higher, with only slight differences in NTE inhibition apparent among the various tissues examined. This extreme inhibition of NTE activity precluded correlation between inhibition of NTE in peripheral leukocytes and the CNS. However, the similarity in NTE response in leukocytes and the CNS following TOCP administration indicates the potential for leukocyte NTE as a biochemical marker for organophosphorus ester-induced delayed neurotoxicity (OPIDN) development. As the distribution pattern of NTE in the CNS of swine closely parallels that of man, these results further suggest that swine may prove a useful animal model for the study of OPIDN. The activity of AChE was highly variable based on time of assay and tissue examined. In general, plasma AChE activity was more severely depressed in all animals and responded more rapidly to TOCP administration. However, erythrocyte AChE more accurately reflected the enzyme's activity in the CNS and the clinical response to TOCP. Based on the data provided by this study, a threshold inhibition of erythrocyte AChE between 59 and 74% is required for production of acute cholinergic signs.

Acetylcholinesterase

Clinical manifestations and leukocyte neurotoxic esterase and red blood cell and plasma acetylcholinesterase activities in swine following a single oral dose of tri-o-cresyl phosphate.

We report the clinical signs and the effects on leukocyte neurotoxic esterase and red blood cell and plasma acetylcholinesterase (AChE) activities in swine orally administered a single dose of tri-o-cresyl phosphate (TOCP) at 400, 800 or 1000 mg/kg. Swine in all dosage groups exhibited signs consistent with inhibition of nervous tissue cholinesterase 3-48 h after TOCP administration. Onset was dose-related, and 2/3 1000 mg/kg dosed swine died 3 or 35 h postdosing. In surviving swine, significant depressions in plasma AChE activity were apparent at 6 h postdosing, ranging from 16-23% of predosing levels. Similar depressions of red blood cell AChE were not observed until 24 h postdosing. Plasma AChE activities appeared to more accurately reflect the development of acute cholinergic signs observed in the 1000 mg/kg dosed swine at 3 h postdosing while red blood cell AChE activities were more consistent with the delayed cholinergic signs exhibited by the 400 and 800 mg/kg dosed swine at 24 h postdosing. All survivors developed signs of delayed neurotoxicity 10-12 d after TOCP administration, and 70% or greater inhibition of neurotoxic esterase activity in leukocytes was apparent during the first 48 h postdosing.

Acetylcholinesterase

The biological activity of glyphosate to plants and animals: a literature review.

Glyphosate is a widely-used broad-spectrum herbicide with little to no hazard to man or the environment. Glyphosate is highly effective against 90 kinds of emerged grasses, brush and broad-leaf weeds. There is no residual soil activity, it does not leach into non-target areas, and it is non-volatile. It is practically nontoxic to mammals, birds and fish, showing no bioaccumulation in the food chain; it is biodegraded into natural products. When used correctly, glyphosate poses no threat to the environment and its inhabitants.

Animals

A literature review of dermatotoxicity.

Dermatotoxicity is the skin's response to chemical substances that produce damage. Penetration of the chemical to the various skin layers is important and may result in irritation, allergic contact dermatitis, contact urticaria, one of various forms of photosensitization, or other cutaneous reactions. The testing of new products or industrial chemicals for potential dermatotoxicity is an important process in protecting the public's health.

Absorption

Immunotoxicity in the bovine animal: a review.

The immune system is a complex biological system involving cellular defenses as well as endogenous and exogenous factors. The potential for immune system exposure to immunotoxins in the environment is well documented. However, caution should be exercised when extrapolating meaningful conclusions from experimental data to assess risk factors to the bovine. Mycotoxins alter immune-mediated activities in cattle and are major immunotoxic risks. Another risk to the bovine is lead. Poor disposal of pollutants in the environment enhances this risk factor. One of the most controllable risk factors is the administration of immunotoxic drugs and biologics. Most of these compounds have minimal immunotoxic activity at recommended dosages. The extra-label use of drugs resulting in super-therapeutic concentrations has increased the probability that certain drugs may act immunotoxicologically.

Adrenal Cortex Hormones

Methylene blue can be used to treat methemoglobinemia in cats without inducing Heinz body hemolytic anemia.

Methylene blue (MB) is the drug of choice in the treatment of methemoglobinemia (MTHB) in humans and most domesticated animals, but is reported contraindicated in cats. Although prolonged treatment of cats for urologic syndromes with MB-containing antiseptics causes Heinz body (HB) hemolytic anemia, there is no evidence to suggest that single or repeated therapeutic doses of MB cause hemolytic anemia. We investigated the efficacy and safety of MB in reversing nitrite-induced MTHB in cats. Forty random-bred adult cats (20 males and 20 females) were divided as follows: Group 1, 1.5 mL saline/kg bw iv (control); Group 2, 1 dose of 1.5 mg MB/kg bw iv; Group 3, 2 doses of 1.5 mg MB/kg bw iv 4 h apart; Group 4 1 dose of 1.5 mg sodium nitrite/kg bw iv; Group 5, 1 dose of 1.5 mg sodium nitrite/kg bw iv followed by 1 dose of 1.5 mg MB/kg bw iv 1 h later; and Group 6, 1.5 mg sodium nitrite/kg bw iv followed in 2 h by 2 doses of 1.5 mg MB/kg iv 4 h apart. One iv dose of MB sufficiently and rapidly reversed MTHB in the cats without increasing circulating HB-containing red blood cells. Giving 2 iv doses of MB without or after sodium nitrite significantly increased the frequency of circulating HB-containing red blood cells. Pre-exposure to sodium nitrite potentiated the HB-inducing effect of 2 doses of MB. Hemolytic anemia was not observed or demonstrated in any of the cats groups.

Anemia, Hemolytic

The effect of various dietary zinc concentrations on the biological interactions of zinc, copper, and iron in rats.

Three groups (14 rats each) were fed one of the following diets for 8 wks: a control purified basal diet containing 12 ppm zinc, 5 ppm copper, and 35 ppm iron; the basal diet with less than 2 ppm zinc; or the basal diet supplemented with 1000 ppm zinc. Rats fed the zinc-deficient diet had decreased weight gain, moderate polydipsia, and intermittent mild diarrhea. The zinc-supplemented rats had a cyclical pattern of food intake and weight loss from weeks 5 to 8. Tissue concentrations suggest that zinc and copper were not mutually antagonistic with chronic dietary imbalances. If tissue element concentrations reflected intestinal uptake, then competition and/or inhibition of intestinal uptake occurred between zinc and iron. The fluctuations in tissue element concentrations that occurred with increased duration of the study were at variance with previous studies of shorter time periods. The dietary proportions of zinc, copper, and iron appear to influence zinc, copper, and iron metabolism at the intestinal and cellular transport levels over a given period of time.

Analysis of Variance

A review of selected herbicides and their toxicities.

Since 2500 BC man has strived to develop methods of orderly pest control (1). These methods included prayer, physical labor, mechanical devices and chemicals. Through chemistry many new pesticides have been developed. Pesticides are "chemicals used to kill a species or a group of species that causes trouble, annoyance or destruction" (2) and include insecticides, rodenticides, fungicides and herbicides. This review focuses on the fastest growing group of pest control agents agents--herbicides. Arsenicals, chlorates, chlorophenoxy acids, biprydyl and substituted phenols are discussed as to their physical and chemical properties, sources, environmental fates, absorption/distribution/elimination, modes of action, toxic effects and recommended treatments.

Animals

Drought increases forage nitrate and cyanide.

To investigate drought-associated increases in concentrations of nitrate and cyanide in animal forage, we compared forage nitrate and cyanide in 1986-87 (annual rainfall 33 in) to nitrate and cyanide in a drought (1988 and 1989; annual rainfall 20 and 27 in, respectively). Fifteen to 20% of the nitrate and cyanide samples from 1986-1987 had sufficiently high concentrations to be of concern (3000 ppm nitrate, 20 ppm cyanide as submitted). Only 4-6% of the 1986-1987 samples had concentrations sufficiently high to produce acute respiratory distress (13,000 ppm nitrate, 50 ppm cyanide as submitted). During 1988 sample numbers had more than doubled, suggesting increased concern for the possibility of nitrate or cyanide intoxication and yielding parallel increases in the number of samples with elevated nitrates or cyanides. By 1989, 25-33% of the samples had concentrations of health concern with respect to either nitrate or cyanide, while 14-19% had concentrations sufficiently high to produce acute respiratory signs. Shortages of forage caused by a 2-y drought were further exacerbated by nitrate and cyanide increases in that feed. Future efforts should concentrate on controlling groundwater nitrate and delivery of nitrate to the plant root-systems.

Animals

A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: II. Copper.

Copper is an essential nutrient for living matter. Through its cuproenzymes, copper displays a variety of metabolic functions. Atomic absorption spectrophotometry, radioisotope studies and establishment of cell and molecular biology have provided the necessary tools to study copper absorption, metabolism, physiology and biochemistry. The vital role of metallothionein in copper homeostasis is examined. Ceruloplasmin represents the molecular link between copper and iron metabolism. The genetic predisposition of copper toxicity has been attributed to the cause of Wilson's disease in humans. The interrelationships between copper and other dietary factors is addressed.

Animals

A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: III. Iron.

Because of its essentiality, iron occurs in tissues of all living matter especially aerobes. Iron compounds have been utilized in various aspects of argo-industry. Iron-binding proteins and their vital role in intestinal uptake, distribution and storage of iron are concisely examined. Ceruloplasmin (cuproenzyme) is imperative for iron mobilization from storage sites for hemoglobin synthesis. There is evidence of relationship between enhance susceptibility to infection and iron deficiency. The extent to which behavioral abnormalities and iron depletion are related remains to be established. The efficacy of chelating agents such as desferroxamine, bicarbonates and ethylene diamine tetraacetic acid (EDTA) against iron overload has been tested.

Anemia, Hypochromic

A review on biochemical roles, toxicity and interactions of zinc, copper and iron: IV. Interactions.

While the major impetus of most of our present knowledge of these metals emphasizes their deficiencies or toxicities, little has been done on their metabolic interactions. Such interactions acknowledge the importance of nutritional deficiencies or toxicities in the biospheres. The effect of dietary zinc supplementation on the bioavailability of copper and iron is a matter of conjecture. Likewise, further research is needed before a unifying hypothesis can be established on the effect of imbalances or interactions among copper and iron. Such mineral imbalance studies will be of value in determining their dietary requirements and in appraising circumstances in which risk to human and animal health may arise.

Animals

A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: I. Zinc.

Zinc is essential for biological functions of all living matter. Zinc is necessary for growth, appetite, testicular maturation, skin integrity, mental activity, wound healing and immunocompetence. Zinc is required for the metabolic activities of over 70 metalloenzymes. The intestinal competition of zinc with copper, iron, lead, calcium and cadmium may accentuate nutritional deficiencies or toxicities from these environmental metals. A unifying hypothesis is not yet established for the effects or imbalances among these elements. These interactions will be of substantial practical importance in estimating dietary recommendations, in validating prophylactic measures, and in the assessment of situations in which human and animal health may be at risk.

Copper

Chemical risk assessment: a review.

People are exposed to a staggering assortment of chemicals and foreign substances. Potential health risks accompany these exposures. Intelligent, informed decisions are needed on which risks can and should be reduced, eliminated, or simply ignored. Therefore, a method of determining the attendant human health risks involved in chemical exposure is necessary. This need has resulted in the evolution of the risk assessment process which was developed to aid in identifying, characterizing and quantifying risks. Risk assessment today is an essential component of regulatory decision-making. In the context of chemical exposure, risk assessment is an evaluation of the risk in human exposure to chemicals in the environment. Quantitative risk assessment (QRA) is the use of experimental laboratory data and/or human epidemiological data in a process to derive a quantitative value for the estimate of the probability of harm occurring to exposed human populations. It is a sophisticated process involving an array of techniques that can be used to identify potential risks to human health. There are 4 components involved in the formalized risk assessment process--hazard identification, toxicity assessment, exposure assessment and risk characterization. These 4 steps collectively address each of 6 key areas identified as essential in characterizing a risk situation involving a chemical exposure. The process of risk estimation involves uncertainties because there are always gaps in knowledge or a lack in understanding mechanisms. These crucial gaps in knowledge are filled when extrapolations, models or assumptions are used. The uncertainties inherent in the risk assessment process are the basis of arguments against the use of the process. Many of these sources of uncertainty inherent in the risk assessment process are examined herein. These include, but are not limited to, modeling methods, understanding mechanisms and pharmacodynamics, exposure data, assumptions and extrapolations. Some new techniques and approaches being applied to the risk assessment process are examined. These include improved models for extrapolating data and quantifying risks, improved laboratory techniques for investigating pharmacodynamic and mechanistic pathways and advancements in quality and application of epidemiological data. The actual concept of uncertainty is being examined and attempts are being made to directly address, quantify and manage uncertainty.

Animals

Ethylene glycol (antifreeze) poisoning in a free-ranging polar bear.

The bright, fluorescent pink-colored remains of a polar bear were found on an Alaskan island with the gravel and snow adjacent to the bear colored bright purple. Traces of fox urine and feces found nearby were also pink. The pink and purple colors were due to rhodamine B, and ethylene glycol (EG) was present in the soil under the carcass. Evidence is given to suggest the bear consumed a mixture of rhodamine B and EG commonly used to mark roads and runways during snow and ice periods. Such wildlife losses could be prevented by substituting propylene glycol for the EG in such mixtures.

Alaska

A study of iron complexation in a swine model.

The treatment of iron poisoning consists of supportive care and efforts to remove or retard the absorption of iron from the gastrointestinal tract. A standard but rarely challenged treatment is to render the unabsorbed iron less soluble by complexing it with bicarbonate or phosphate solution. Another therapy is the use of oral deferoxamine. Bicarbonate and phosphate therapy are known to be associated with adverse outcomes if used inappropriately. Is their use justified? To closely simulate a potentially toxic iron overdose in a 24-month-old child, a swine model was used. Twenty fasted castrated male pigs weighing an average of 14.6 kg (+/- 3.0 kg) were orally dosed with 300 mg/kg FeSO4 (60 mg Fe/kg) and randomly placed into 1 of 4 treatment groups receiving 50 ml of distilled water (control), 5% sodium bicarbonate, 5% sodium dihydrogen phosphate, or deferoxamine (10 g). Sequential serum iron levels were obtained at 0, 1, 2, 4, and 6 hr. There were no significant differences in the absorption of iron, as reflected by serum iron concentrations, in the bicarbonate and phosphate groups when compared to the control group (p greater than 0.05). Deferoxamine therapy reduced iron serum concentrations, ie iron absorption, significantly (p less than 0.05) when compared to the control, bicarbonate and phosphate groups. This study provides evidence that efforts to form digestive tract complexation of iron with bicarbonate or phosphate are of no value.

Administration, Oral

An investigation of metaldehyde and acetaldehyde toxicities in dogs.

Acetaldehyde has been reported, but has not been proven, to be the toxic entity resulting from metaldehyde ingestion. To investigate this, male dogs were given a single dose of 600 mg metaldehyde or acetaldehyde/kg of body wt via stomach tube. Clinical signs were monitored, and plasma and urine were assayed for metaldehyde and acetaldehyde. Vomiting occurred less often and in a significantly lower number of metaldehyde-dosed dogs than in acetaldehyde-dosed dogs. Ataxia and tremors occurred significantly more often in metaldehyde-dosed dogs than in acetaldehyde-dosed dogs. Acetaldehyde was not detected in the plasma or urine of metaldehyde-dosed dogs, however, it was found in a sample of vomitus from one of the metaldehyde-dosed dogs. Metaldehyde was found in plasma and urine of metaldehyde-dosed dogs. Urinary excretion of metaldehyde from the metaldehyde-dosed dogs was less than 1%. Urinary excretion of acetaldehyde from acetaldehyde-dosed dogs was essentially nonexistent. Metaldehyde has a larger role in the mechanism of metaldehyde toxicity than previously thought. While acetaldehyde appeared to be of significantly lesser importance, we could not eliminate it as a factor in metaldehyde toxicity in dogs.

Acetaldehyde