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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

Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet, and permethrin: implications of Gulf War chemical exposures.

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/wk for 2 months to 5 mg/kg/d PB in water, po; 500 mg/kg/d DEET, neat, sc; and 500 mg/kg/d permethrin in corn oil, sc). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB "pumps" more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of near-lethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important "buffering" role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neurologic deficits produced by exposure to certain chemical mixtures.

Administration, Oral

Iron complexation with oral deferoxamine in a swine model.

A controversial therapy in the management of acute iron poisoning is the oral administration of deferoxamine which purportedly complexes unabsorbed iron, exerts protection at the cellular level, and/or enhances the renal elimination of ingested iron. To study the effects of oral deferoxamine on iron absorption, fasted male pigs weighing an average of 10 kg simulated potentially toxic iron overdoses in 12 to 24-mo-old children. A control group of 13 pigs received 60 mg elemental iron/kg via oral gavage followed by 50 ml of distilled water. Serum iron (SI) levels were obtained at 0, 1 2, 4, 6 and 8 h post-iron dosing. The study group of 10 pigs received 60 mg elemental iron/kg po followed by 10 g deferoxamine (1 g/kg). SI levels were obtained at the same intervals. There was no mortality in either group. Statistical differences in SI were noted at 6 and 8 h. Characteristic urine discoloration secondary to deferoxamine was noted at 4 h in the study group. Deferoxamine reduced some peak 51 levels but did not diminish the total absorption of iron.

Administration, Oral

A review of the toxicology of air pollutants: toxicology of chemical mixtures.

On a temporal basis, air has immense capacity for moving a large mass of pollutants. Mammals and birds are exposed to pollutants in air by the inhalation (nose and mouth), cutaneous or ocular routes. Most laboratory studies on air pollutants have been limited to single air pollutants and very little research has been done on the complex mixture of compounds that exist in ambient air. Complex mixtures are further complicated by dynamic chemical reactions that occur after the emissions leave point sources. Exposure parameters are also important in the toxicity of air pollutants. Intermittent exposure of monkeys to ozone increased the adverse pulmonary effects. Superimposing spikes of 0.8 ppm nitrogen dioxide on a baseline of 0.2 ppm, as occurs on a calm winter day, increased the susceptibility of mice to bacteria-induced pneumonia. Sulfur dioxide at concentrations of 5 ppm increased pulmonary resistance by 39%. Sulfuric acid is the predominate acid particle in the atmosphere. Exposure for 1 h to > 200 micrograms sulfuric acid/m3 depressed bronchomucociliary clearance. Concentrations of 100 micrograms/m3 of photochemical products caused headaches and 510 micrograms/m3 produced cough and chest pain. For chemical interactions in dose response, nitrogen dioxide is synergistic with ozone and ammonium sulfate. When all 3 chemicals are used in mixture, the response was 340%. Atmospheric conditions, such as fog, can alter the toxicity of air pollutants. The dose response to a single chemical can be altered by chemical mixtures and pre-existing disease conditions. Understanding these relationships is important for establishing no observable adverse effect levels. Mechanisms for multiple chemical interactions are multifaceted. One chemical may interfere with the metabolism or detoxification of another. Others may interact at cell receptors. To understand the effects of multiple chemical interactions of air pollutants, there is a need for a blend of epidemiological, laboratory and field studies. Studies are expensive. In the rural agricultural settings, the economic and environmental health risks are high. Should field observations and chemical problems be used as "red flags" for action?

Air Pollutants

Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats.

Acetaminophen is widely used in human beings for analgesic purposes, but is one of the most frequent causes of poisoning in cats. Acetaminophen-poisoned cats develop methemoglobinemia and sometimes hepatic failure. To determine the benefit of using methylene blue, a treatment for methemoglobinemia, along with N-acetylcysteine (NAC), the recommended treatment for acetaminophen-poisoned cats, groups of 3 male and 3 female cats each were given methylene blue NAC, or both after administration of acetaminophen (120 mg/kg of body weight, PO). Male cats seemed more susceptible than female cats to acetaminophen toxicosis, because 3 males died of hepatic failure (2 cats given acetaminophen/methylene blue and 1 given acetaminophen/NAC/methylene blue). Although NAC alone seemed to elicit the best overall response, methylene blue, alone or in combination with NAC, may be useful in female cats.

Acetaminophen

Total and respirable dust in swine confinement buildings: the benefit of respiratory protective masks and effect of recirculated air.

Caretakers and pigs in dusty environments inhale particles and toxic gases which can cause subclinical illness. We determined the reduction in sampled dust elicited by respiratory masks mounted on glass funnels. Open-faced filters or British cyclones were sampled to measure quantities of dust which the masks had trapped. Respiratory masks reduced the sampled total suspended particulates (open-faced filters) by > or = 75% with NIOSH/MSHA certified protectant (2-tie) masks and > or = 50% with NIOSH/MSHA non-certified comfort (1-tie) masks. Respirable particulates (British cyclones) were reduced by > or = 45% with NIOSH/MSHA certified protectant (2-tie) masks. These data suggest properly worn respiratory protective masks afford significant protection against both total suspended and respirable particulates in swine confinement facilities. Penetration of 3-25% of total aerosol mass through masks allowing only 1% penetration of a silica aerosol with an aerodynamic diameter of 0.6-1.0 microns suggested that measurable portions of the aerosol mass in these confinement houses behaved as if they were less than 1 micron in diameter. Because of the small size of the aerosol, NIOSH/MSHA certified respiratory protective masks should be worn when working in those facilities. We also studied concentrations of ammonia, endotoxin and total and respirable dust particles to determine effects of a recirculation fan which increased the nominal air flow capacity of the building by 10%. Recirculated air had minimal effects on ammonia, total airborne endotoxin or total particulate mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Conditioning

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

Characterization of particles, ammonia and endotoxin in swine confinement operations.

To define the atmospheres swine confinement operations, we measured concentrations of total and respirable dust particles, ammonia and endotoxin in the nursery and grower areas of 4 swine confinement houses. Increased ventilation in spring-summer relative to that in winter reduced concentrations of large dust particles more rapidly than it did smaller particles or ammonia. The greater decrease in large particles correlating to increased room air velocity may reflect larger particles' momentum causing impaction on surfaces. There was significant spatial variation in the concentration of airborne endotoxin within individual swine rooms and pens reflecting different mixing of large feed and smaller manure particles. Smaller particles had 4-fold higher concentrations of endotoxin than did larger particles, suggesting they had higher fecal material concentrations. Total airborne endotoxin and total suspended particulates correlated to the fraction of functional endotoxin contained in large particles, suggesting that small particles (0.5-2.0 micrometers) collide with large particles (50 micrometers). These data suggest that large non-respirable particles remove smaller respirable particles from indoor atmospheres due to kinematic coagulation.

Air Pollution, Indoor

A review of thallium toxicity.

Thallium (Tl) is one of the most toxic of the heavy metals. Its continued use as a rodenticide in many developing countries and its increasing use in an expanding number of new technologies raise concerns about exposure risk to animals and humans. Because Tl and potassium (K) have the same charge and similar ionic radii, Tl follows K distribution pathways and alters and number of K-dependent processes. Possible toxic mechanisms of Tl include ligand formation with protein sulfhydryl groups, inhibition of cellular respiration, interaction with riboflavin and riboflavin-based cofactors, and disruption of calcium homeostasis. The principal clinical features of thallotoxicosis are gastroenteritis, peripheral neuropathy of unknown etiology, and alopecia. The presence of elevated Tl levels in the urine or other biologic materials confirms the diagnosis of Tl poisoning. Treatment with prussian blue (or activated charcoal) will interrupt the enterohepatic cycling of Tl, thus enhancing fecal elimination of the metal. Forced diuresis with potassium loading will increase the renal clearance of Tl, but should be used cautiously because neurologic and cardiovascular symptom may be exacerbated. If recognized and treated early, Tl poisoning carries a favorable prognosis for full recovery.

Animals

Ototoxicity in dogs and cats.

Ears are special sense organs whose principal functions are hearing and maintaining equilibrium. Aminoglycoside antibiotics, erythromycin, polymyxin B, and cisplatin can affect either or both of these functions by binding with, injuring, and/or destroying special receptor cells associated with these functions. Severe hearing loss manifests itself as deafness, whereas loss of equilibrium will present as abnormal righting reflexes, nausea, and vomiting. Damage is proportional to levels of these ototoxins in the endolymphatic fluids. Evidence suggests that toxicity may be influenced by endolymphatic calcium concentrations, and levels of cAMP and cGMP are altered in specialized cochlear cells during ototoxicity, suggesting an additional mechanism for ototoxicity. The administration of salicylates and loop diuretics may potentiate the action of ototoxins, especially aminoglycoside antibiotics, probably by increasing the levels of these toxins in the endolymphatic fluid. Although many of these assessments have been made in laboratory animals, applicability may also be expected in small domestic animals, and extreme care should be taken in prescribing potentially ototoxic drugs to small animals. Cochlear damage from ototoxic compounds occurs initially in the cells detecting high-frequency sounds located at the lower basal region. In aging dogs and humans, this sensitivity of receptors in the lower basal region is enhanced. Early auditory damage is detectable by BAER and cochlear microphonic potentials. Vestibular responses can also be detected early as vestibular ocular reflexes and visual-vestibulo-ocular reflexes. Early detection is especially important because early changes can sometimes be reversible. Cavinton (apovincaminic acid) and fosfomycin represent examples of experimental agents being evaluated in laboratory animals for application as potential treatments to limit the ototoxicity associated with various drugs.

Aminoglycosides

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