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Biomedical subjects

H D Mercer

Publications and source records attributed to H D Mercer.

At least 19 recordsLinked to original sources

Biological effects of electric fields on agricultural animals.

The biological effects of electric fields has been intensively studied in laboratory animals. Most of the effects relating to exposure to electric fields have been observed under artificial conditions and at exceptionally intense fields (40-100 kV/meter). Few studies have been completed in agricultural animals, yet this class of animal probably receives the greatest exposure under actual field conditions. The objective of this paper was to summarize the available scientific data for agricultural animals. Based upon limited experimental data, and a number of years experience with animals under high-voltage lines, it appears that electric fields of 10 kV/m or less do not represent a biological hazard to agricultural animals.

Animals↗

Excretion of [3H]prednisolone in clinically normal and experimentally infected bovine udders.

The excretion rate of [3H]prednisolone from clinically normal and experimentally infected udders of 10 lactating cows was studied. Each quarter of 6 cows was injected with a single dose of [3H]prednisolone mixed with non-radioactive prednisolone equivalent to 10 mg in 10 ml of peanut oil base. Each of the remaining 4 cows was given 40 mg of nonradioactive prednisolone and [3H]prednisolone in 60% ethanol IV. Control and postadministration samples of blood, milk, and urine were examined for radioactivity. The effects of [3H]prednisolone were evaluated in the same cows, first in clinically normal udders, then 2 weeks later in udders experimentally infected with Streptococcus agalactiae. Absorption and elimination of prednisolone were the same before and after induced infection. Within 3 hours after intramammary injection, 95% of the labeled prednisolone was absorbed systemically, less than 5% of this dose was recovered in milk, and 29% was excreted in urine. After IV injection of [3H]prednisolone, less than 0.2% of the total radioactivity was recovered in milk and less than 46% was excreted in urine. Clinical mastitis induced by S agalactiae was moderate. Circulating blood leukocytes and somatic cells in the milk of normal cows remained essentially unchanged. The leukocyte response to induced infection was rapid in blood and milk. Large numbers of leukocytes were noticed in the milk and a severe leukopenia occurred. Prednisolone treatment did not alter the number of somatic cells in milk or reduce the inflammatory response of experimentally infected cows.

Animals↗

Jimson weed seed toxicity in cattle.

A subacute experiment was undertaken for 14 days. The results obtained from these studies suggest that: 1) unless a highly Jimson weed seed contaminated feed is ingested (greater than 0.09% of body weight) or force fed, death should be a rare consequence of Jimson weed seed contamination; 2) Jimson weed seed toxicity in cattle as a result of feed contamination appears a self-limiting problem (rumen atony and anorexia prevent further intoxication until the blood levels of alkaloids are reduced to allow normal ruminant intestinal function); 3) cattle may exhibit signs of atropine toxicity at contamination levels of 881 seed/kg of feed or higher; 4) rumen fluid from heifers fed diet containing 4,408 Jimson weed seed had the greatest VFA concentration change from day 0 to 7; 5) in vitro fermentation of diets resulted in no difference in IVDMD values, but VFA concentration values tended to increase with increased concentrations of Jimson weed seed in the diet.

Alkaloids↗

Use of the double-isotope single-injection method for estimating renal function in normal cross-bred swine.

The double-isotope single-injection method to estimate renal function which utilizes the radiolabeled chemicals [131I]sodium iodohippurate and [125I]sodium iothalamate was evaluated in swine. A total of 46 normal, cross-bred swine were used to determine the applicability of this method for measuring the glomerular filtration rate and effective renal plasma flow. The mean glomerular filtration rate in pigs was determined to be 5.33 +/- 0.82 ml/kg of body weight/minute for [125I]sodium iothalamate with a biological half-life (T 1/2) of 39.18 +/- 7.44 minutes. The mean effective renal plasma flow was determined to be 19.25 +/- 3.12 ml/kg of body weight/minute for [313I]sodium iodohippurate, with a T 1/2 of 18.45 +/- 1.74 minutes. These values are more closely related to the glomerular filtration and effective renal plasma flow values reported for dogs and cats than they are to values reported for man. The method is rapid and reliable; results are available 6 to 8 hours after the experiment. This method is advantageous when information about renal function variables is a prerequisite to pharmacokinetic or toxicologic studies.

Animals↗

Effect of feeding chlortetracycline on the reservoir of Salmonella typhimurium in experimentally infected swine.

Swine were fed either a diet containing 110 mg of chlortetracycline (CTC) per kg (100 g/ton) or a control diet and were inoculated orally with Salmonella typhimurium that was either susceptible or resistant to CTC. The quantity, duration, and prevalence of fecal elimination of S. typhimurium, as well as the effect of CTC on the transmission of S. typhimurium from infected to uninfected swine, were determined. When animals were infected with CTC-resistant S. typhimurium, CTC increased the quantity (P < 0.05), duration (P < 0.05), and prevalence (P < 0.01) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. When animals were infected with CTC-susceptible S. typhimurium, CTC reduced the quantity (between 7 and 10 days postinfection) (P < 0.01), duration (P < 0.05), and prevalence (P < 0.05) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. Resistance to tetracycline was transferred in vivo to 4 and 6% of the susceptible infecting S. typhimurium recovered from the untreated and treated groups, respectively. The increased reservoir of S. typhimurium and the transfer of resistance to susceptible S. typhimurium have implications for both animal and public health.

Animal Feed↗

Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry.

Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5-1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with (131)I-sodium-iodohippurate and (125)I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained.

Animals↗

Use of the double-isotope, single-injection method for estimating renal function in normal and polybrominated biphenyl-exposed dairy cows.

A method is described for conducting a rapid and efficient renal function test in dairy cattle. The method, adapted from methods used for man and dogs, utilizes radiolabeled 131I-sodium iodohippurate to determine effective renal plasma flow (ERPF) and 125I-sodium iothalamate to determine glomerular filtration rate (GFR). The mean GFR for adult cattle was determined to be 2.8 +/- 0.4 ml/kg/minute with a biological half-life of 35.5 +/- 1.4 minutes. The mean ERPF was found to be 10.5 +/- 1.9 ml/kg/minute with a half-life of 17.9 +/- 0.6 minutes. These values are comparable with those in man, but are lower than values in dogs. A toxcity study was done with dairy cattle exposed to polybrominated biphenyls (PBB). Efforts were made to determine the amount of time required for kidney lesions to develop and, if possible, to delineate the potential site of action of PBB. Apparently PBB do not affect GFR or ERPF, even though they produce nephrotoxic effects. Potential mechanisms to explain these results are described.

Animals↗

Influence of chlortetracycline feeding on salmonellosis in calves. I. Rate and duration of shedding. II. Severity of illness.

Studies were conducted to test the influence of the feeding of chlortetracycline (CTC) on the fecal shedding of S. typhimurium subsequent to experimentally induced infection in calves. Levels of 0, 20, 50, and 100 gm CTC per ton of feed were fed to groups of calves for a two-week period before inoculation and the resulting level of shedding of S. typhimurium quantified. At the 50 gm/ton level, the feeding of CTC was associated with a significantly higher level of shedding than in non-CTC fed controls, and the duration of shedding was longer. Calves fed at 50 and 100 gm CTC/ton were affected much more severely by the inoculation than calves receiving no CTC. The same was true to a lesser extent in the calves fed 20 gm/ton. Observations made on each calf included changes in body temperature, time of onset, severity and duration of diarrhea, straining, and anorexia. Since the fecal output of salmonellae is increased at the level of 50 gm/ton, the authors conclude that this commonly used level of CTC feeding in calves contributes to the size of the salmonella reservoir in nature, thus increasing the risk of exposure to both man and animals alike and otherwise complicates the problems of salmonellosis.

Animal Feed↗

Pathology of experimentally induced polybrominated biphenyl toxicosis in pregnant heifers.

Toxicosis was induced in pregnant Holstein-Friesian heifers by giving polybrominated biphenyls a in gelatin capsules at the rate of 25 g/day. Initially, this dosage was approximately 67 mg/kg of body weight. Clinical signs were anorexia, excessive lacrimation and salivation, diarrhea, emaciation, dehydration, depression, and abortion. Fever was not evident during the experiment. Values for serum glutamic-oxalacetic transaminase, lactic dehydrogenase, blood urea nitrogen, and bilirubin were increased. Changes in packed cell volume, hemoglobin content, total erythrocyte and leukocyte counts, and differential leukocyte counts were minimal and reflected dehydration and secondary infection. The principal urine changes were decreased specific gravity and moderate proteinuria. Gross necropsy findings included dehydration; subcutaneous emphysema and hemorrhage; atrophy of the thymus; fetal death with concomitant necrosis of cotyledons; kidneys that were enlarged, pale tan to gray; thickened wall of the gallbladder; inspissated bile; edema of abomasal folds; mucoid enteritis; linear hemorrhage and edema of the rectal mucosa; and secondary pneumonia. Microscopic changes were most marked in the kidneys, gallbladder, and eyelid. In the kidney, the principal changes were extreme dilatation of collecting ducts and convoluted tubules, with epithelial degenerative changes of cloudy swelling, hydropic degeneration, and separation from the basement membrane. Common changes in the gallbladder were moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria. The changes in the eyelids were characterized by hyperkeratosis, with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands. Clinical signs and lesions of toxicosis did not develop in heifers given the polybrominated biphenyls at the rate of 0.25 mg and 250 mg/day for 60 days. Initially these rates were approximately 0.00065 mg/kg and 0.65 mg/kg of body weight, respectively.

Animals↗

Factors affecting serum oxytetracycline levels in beef calves.

Fifteen Aberdeen Angus steers, 295-364 kg, were dosed with either 4.4 or 11 mg of oxytetracycline hydrochloride/kg im. The antimicrobial activity of the serum was determined periodically, and the resulting data were treated statistically to determine the sources of variation. Variance in serum levels of oxytetracycline activity was attributed to dose, time of bleeding, order of dosing, animal, and assay. The total variance component was proportionately greater for the 11-mg/kg dose than for the 4.4-mg/kg dose. Animal variance increased with the higher dose level of oxytetracycline. The influence of dose on serum level was tested by applying a t test to the mean serum levels and their standard deviations at each bleeding time. The 4.4- and 11-mg/kg serum levels were significantly different (p less than 0.01) at all bleeding times. The 4.4-mg/kg serum levels mutliplied by 2.5 were not significantly different (p less than 0.05) from the 11-mg/kg serum levels at all bleeding times.

Animals↗

Application of pharmacokinetic methods to the drug residue profile.

A pharmacokinetic approach to the delineation of a drug residue profile in food-producing animals has been presented. It is recognized that the determination of a drug withdrawal period is one of the costly developmental procedures in drug development for food animals; thus it is believed that in the early developmental phases, a thorough pharmacokinetic characterization of a drug in the target species would greatly facilitate the design and quality of studies conducted in the later phases of new drug development. It is suggested that drugs that are intended for use in food animals can be characterized kinetically in less costly studies, the results of which might be used to determine the feasibility of developing a drug that might cause serious residue problems. It is also suggested that the pharmacokinetic modeling of a drug in the target animal may provide an essential data base for calculating dosage rates and intervals that directly relate to the efficacy aspects of drug development.

Animals↗

Effects of polybrominated biphenyls on health and performance of pregnant Holstein heifers.

The toxicity of a commercial blend of polybrominated biphenyls was determined in 24 pregnant Holstein heifers that were allotted randomly to one of four experimental groups given 0, .25, 250, or 25,000 mg/day of fire-Master BP-6. The polybrominated biphenyls were mixed with finely ground corn and given by bolus for 60 days or until the animal became moribund. Average body weight of heifers at onset of experiment was 381 kg. No clinical signs of toxicosis were evident in heifers fed 0, .25 or 250 mg/day. Toxicosis was induced in heifers fed 25,000 mg/day resulting in reduced dry matter intake, body weight, heart rate, and respiration rate. Clinical signs were anorexia, emaciation, dehydration, excessive lacrimation and salivation, diarrhea, depression, and abortion or fetal death. All heifers fed 25,000 mg/day became moribund within 33 to 66 days.

Abortion, Veterinary↗