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Biomedical subjects

D J Schaeffer

Publications and source records attributed to D J Schaeffer.

At least 73 records · Page 4Linked to original sources
PubMed1992

Different neuroendocrine systems modulate pulsatile luteinizing hormone secretion in photosuppressed and photorefractory ewes.

The objective of this study was to determine whether two photoperiod regimens that induce anestrus in the ewe-short-day photorefractoriness (SDPR) and long-day photosuppression (LDPS)--act by different neuronal mechanisms. In separate experiments, ovary-intact (INTACT), ovariectomized (OVX), and ovariectomized estradiol-treated (OVX + E) ewes were subjected to three different photoperiodic regimens that resulted in reproductive quiescence: (1) exposure to long days (16L:8D), which caused photosuppression (INTACT, n = 9; OVX, n = 6; OVX + E, n = 5; (2) prolonged exposure to short days (10L:14D)), which caused photorefractoriness (INTACT, n = 10; OVX, n = 6; OVX + E, n = 5); (3) exposure to natural photoperiod, which induced seasonal anestrus (INTACT, n = 11; OVX, n = 6; OVX + E, n = 5). Effect of photoregimen was monitored by measuring progesterone or LH. Drug challenges were made after two sequential estrous cycles were missed in INTACT ewes, after mean LH concentrations dropped below 1 ng/ml in OVX + E ewes, and after LH interpulse intervals increased in OVX ewes. Effects of drug on LH pulse pattern were determined by taking blood samples at 12-min intervals for 8 h after i.v. diluent injection; then for 8 h after i.v. injection of cyproheptadine, a serotonin antagonist (3 mg/kg); and again 7 days later after i.v. injection of diluent or pimozide, a dopamine antagonist (0.25 mg/kg). Cyproheptadine had little effect except to decrease (p = 0.05) mean LH in INTACT anestrous ewes and decrease (p less than 0.01) pulse amplitude in OVX + E SDPR ewes. Pimozide did not affect LH pulse frequency in LDPS ewes. However, pimozide increased LH pulse frequency (p less than 0.005) and mean concentrations (p less than 0.005) in SDPR OVX + E ewes, whereas it suppressed LH pulse frequency (p less than 0.05) and amplitude (p less than 0.03) in SDPR INTACT and SDPR OVX ewes. The results suggest that (1) the role of the dopaminergic system differs in SDPR and LDPS ewes, and that different neuronal systems may effect SDPR and LDPS, (2) the effect of pimozide in SDPR ewes is altered by ovarian steroids, and (3) the serotonergic system has relatively little role in regulating pulsatile LH secretion in any of the three different states of anestrus.

Animals↗
PubMed1992

A scientific basis for proposed quality assurance of a new screening method for tumor-like growths in the planarian, Dugesia dorotocephala.

Various abnormal growths appear on planarians, Dugesia dorotocephala, during and after exposure to polychlorinated biphenyls (PCBs) 28, 110, and 126; Aroclor 1254; cadmium sulfate; and L-buthionine-(R,S)-sulfoximine (BSO). Daily observations under magnification were used to describe the location, development, and morphology of three different types of tumor-like growths ("tumors"). "Post-head tumors" were found to be highly invasive, progressive, and lethal to the animal depending on concentrations and combinations of the compounds used. Survivors from post-head tumors exhibited aberrant morphogenesis, but developmental abnormalities were eventually shed. Post-head tumors occurred within 2 weeks of initial exposure, while "round tail tip tumors" appeared after 2-3 weeks. The rate of progression and invasiveness was greater for the round tail tip tumors. "Pigmented rose thorn tail tumors" occurred in low incidence (4-20%) and appeared to be harmless and noninvasive, requiring months to develop from the first appearance of pigmentation. The aggressive, proliferative, and invasive characteristics of post-head and round tail tip tumors are analogous to those of malignant tumors, while pigmented rose thorn tumors were benign. High dose of cadmium alone were sufficient to initiate the post-head and round tail tip tumors. PCBs potentiated the tumorigenicity of low cadmium doses and enhanced the very low spontaneous incidence of pigmented rose thorn tumors. PCBs also impaired motor activity, causing the graceful gliding locomotion to be replaced by a twisting serpentine movement accompanied by muscular dystrophy. In addition, high (50 micrograms) doses of PCB 110 depressed activity, while lower (5 micrograms) doses and 50 micrograms Aroclor 1254 induced restlessness and enhanced locomotion. These data provide the basis for quality assurance.

Animals↗
PubMed1992

Serum haptoglobin concentration as an indicator of weight gain in pigs.

Serum haptoglobin concentration was investigated as an indicator of weight gain in commercially-reared pigs. The serum haptoglobin concentrations and weights of 40 pigs were monitored on a weekly basis, from weaning to 13 weeks of age. All data were ranked based on the week 13 weights, and divided into high, middle and low weight gain groups. By the fourth week of the study, when the pigs were seven weeks old, serum haptoglobin concentrations could be used to differentiate pigs that would have a high weight gain at the end of the study from those which would have a low weight gain.

Analysis of Variance↗
PubMed1991

Electromyographic assessment of the neuromuscular blockade produced in vivo by anatoxin-a in the rat.

The indirectly evoked compound action potentials (ECAP) of the plantar muscles of the rat were used to investigate the pharmacodynamics in vivo of the neuromuscular blockade produced by anatoxin-a. Onset time to maximum depression and the magnitude of maximum depression in amplitude of the ECAP were dose-dependent. The mean maximum percent depression (+/- S.D.) of the ECAP induced by single, supramaximal stimulations of the posterior tibial nerve after i.v. doses of (+)anatoxin-a hydrochloride at 0, 50, 100, 200 and 800 micrograms/kg were 3 (4), 53 (15), 82 (7), 95 (2), and 100 (1), respectively. The ED50 (95% confidence limits) for depression of the ECAP was 47 mg/kg (39-57 micrograms/kg). Rats administered 200 micrograms/kg or less of (+)anatoxin-a hydrochloride had 75% return of the pretoxin amplitude of the ECAP within 93 min. Animals dosed at 800 micrograms/kg did not have return of neuromuscular function and died despite mechanical ventilation, suggesting a lethal mechanism(s) of action in addition to respiratory paralysis. Percent decrements (+/- S.D.) in the amplitude of the fourth ECAP following repetitive stimulation at 10 Hz were 6 (5), 13 (22), 46 (18) and 59 (8) from (+)anatoxin-a hydrochloride given i.v. at 0, 50, 100 and 200 micrograms/kg, respectively. The decrement observed following repetitive stimulation was attributed to a presynaptic site of action. No change in maximal motor nerve conduction velocity or latency of the ECAP was observed after i.v. administration of (+)anatoxin-a hydrochloride at 100 micrograms/kg. LD50 values (95% confidence limits) for anatoxin-a administered i.v. to mice were 386 micrograms/kg (365-408 micrograms/kg, for (+)anatoxin-a hydrochloride and 913 micrograms/kg (846-985 micrograms/kg) for racemic anatoxin-a hydrochloride. No deaths were observed in mice after i.p. administration of (-)anatoxin-a hydrochloride at doses up to 73 mg/kg.

Action Potentials↗
PubMed1991

A toxicological perspective on ecosystem characteristics to track sustainable development. VII. Ecosystem health.

"Ecosystem health," an emerging science paralleling human and veterinary medicine, has as its goals the systematic diagnosis and treatment of stressed ecosystems. Ecosystems are stressed by physical factors such as boat traffic, biological factors such as introduction of an exotic species, and chemical factors such as pH change. Even if these classes of stressors affect the same trophic levels, the resulting ecosystem disease states have different etiologies because the stress is introduced and propagated by different mechanisms. This paper presents a toxicological perspective on ecosystem sustainability. I discuss how classical toxicological concepts have to be modified when the experimental unit is an ecosystem. When exposures are high, effects are acute and are often measurable (e.g., fish kill). However, when exposures are low and chronic, effects are often hard to separate from the background. Evidence of high risk for lack of sustainable development is the exceeding of ecosystem "threshold criteria."

Biomarkers↗
PubMed1991

Radiographic and histologic effects of chondroitinase ABC on normal canine lumbar intervertebral disc.

Twelve dogs were divided into two equal groups and given lumbar intradiscal injections of 10, 50, or 100 U/ml of chondroitinase ABC reconstituted in sodium acetate buffer. Radiographs of the lumbar spine were made before and after surgery in both groups. Additional films were made at 5 days after surgery in Group I and at 7, 14, and 21 days after surgery in Group II. All spaces injected with 50 or 100 U/ml chondroitinase ABC demonstrated significant radiographic narrowing in both groups compared with uninjected control and buffer injected discs (P less than 0.001). Discs injected with 10 U/ml of chondroitinase ABC showed increased narrowing over time from 7 to 21 days (P less than 0.05). A zone of safranin O depletion was present in the ventral anulus fibrosus adjacent to the nucleus pulposus in all treated discs, indicating proteoglycan loss. All histologic effects of chondroitinase ABC were confined to intervertebral disc tissues. Chondroitinase ABC appears to be effective for chemonucleolysis in dogs.

Animals↗
PubMed1991

Nuclear imaging of the stomach of healthy dogs.

To evaluate the use of technetium pertechnetate (99mTcO4) as a means of estimating gastric mucosal integrity, nuclear images of the empty stomach were obtained from 6 dogs at 20, 40, 60, 120, 180, and 240 minutes after IV administration of the radiopharmaceutical. Blood and gastric secretion samples were collected during the same time intervals. The left lateral-view image of the stomach was used to calculate the relative fraction of the dose in the stomach and the count density ratio. Between 20 and 40 minutes and 40 and 60 minutes, significant differences (P less than 0.001) were apparent in the amount of 99mTcO4 in the stomach. Blood concentration of 99mTcO4 decreased significantly (P less than 0.001), whereas gastric secretion concentration increased significantly (P less than 0.001) over time. Qualitative assessment of the gastric nuclear scans and the statistical analytic results indicated that the optimal time for imaging the canine stomach was between 40 and 60 minutes after radiopharmaceutical administration. In a second study, the same dogs were pretreated with the H2-receptor antagonist cimetidine and the cholinergic antagonist glycopyrrolate to block gastric secretions. Over time, changes in the relative dose fraction in the stomach and the density ratio were the same as values obtained during the experiment performed without use of cimetidine and glycopyrrolate. Results of the study indicate that nuclear imaging with 99mTcO4 outlines normal canine gastric mucosa and that pretreatment with cimetidine and glycopyrrolate has no effect on the quality of the gastric image.

Animals↗
PubMed1991

Use of a nuclear imaging technique to detect gastric wall ischemia.

A nuclear imaging technique of the stomach, using technetium pertechnetate (99mTcO4), was evaluated in healthy dogs. The stomach was first insufflated with room air, then filled with barium sulfate to induce mild distention, outlining the gastric wall. Six dogs were imaged twice: initially without use of drugs that might affect gastric secretion of 99mTcO4, then after pretreatment with cimetidine and glycopyrrolate. These scans established the appearance of the normal (control) stomach and compared the quality of the image in the same dogs not pretreated, then pretreated with cimetidine and glycopyrrolate before administration of 99mTcO4. Avascular defects were then surgically created on the greater curvature of the stomach of the same 6 dogs, and gastroscintigraphy was performed in similar manner. Significant (P less than 0.05) quantitative differences were detected in the gastric images for scans of the avascular area, compared with various control scans. Qualitative assessment had overall accuracy of 90.28%. Results of the study reported here indicate that nuclear imaging can be a valuable diagnostic technique for detecting ischemic areas in the gastric wall of dogs.

Animals↗
PubMed1991

Cocarcinogenesis between cadmium and Aroclor 1254 in planarians is enhanced by inhibition of glutathione synthesis.

Asexual Dugesia dorotocephala planaria continuously exposed to 50 micrograms/beaker of Aroclor 1254 (A1254) and cadmium (Cd) developed tumors after 11 days of continuous exposure to 0.65 or 1.3 mg/liter Cd and after 23 days to 0.13 mg/liter Cd. The tumor rate at 14 days averaged 53% for the survivors in both 0.65 and 1.3 mg/liter Cd + A1254 and 40% at 0.13 mg/liter Cd + A1254. Other groups were either preexposed or coexposed to L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione synthesis. In the presence of A1254 (50 micrograms/beaker), animals continuously exposed to BSO and 0.13 mg/liter Cd first developed tumors at 18 days, with a tumor yield equal to 41% of the survivors. Tumors developed by 6 days at 0.65 mg/liter Cd, with a yield equal to 75% of survivors. At 1.3 mg/liter Cd, BSO did not change the rate or frequency of planarian tumor production. Continuous BSO always produced high mortality over 20 days. In contrast, a 24-h preexposure to BSO caused little mortality. In these groups, tumor yields increased with cadmium concentration (0.13, 0.25, 0.65 mg/liter), and the large cocarcinogenic effect of A1254 was clearly evident. No tumors developed in animals exposed only to 50 micrograms/beaker of Aroclor 1254 or continuously only to 1 mM BSO.

Animals↗
PubMed1990

An experimental model for pharmacokinetic analysis in renal failure.

A renal failure model was developed in the dog to evaluate the effect of varying degrees of renal failure on drug pharmacokinetics. A controlled impairment of renal function was induced by electrocoagulating portions of one kidney and excising the contralateral kidney. The magnitude of renal dysfunction, defined by the percentage of normal glomerular filtration rate (% NGFR), was estimated by 125I-iothalamate total body clearance. The model was evaluated by comparing the pharmacokinetics of oxytetracycline (OTC) before and after the induction of renal failure in two experiments: single intravenous dose (11 dogs); single intravenous and oral doses (8 dogs). Renal failure (RF) was studied in three classes according to % NGFR: less than 25%, severe RF; 25-39%, moderate RF; and greater than or equal to 40%, mild RF. Significant reductions were observed over RF class in OTC pharmacokinetic parameters for elimination and distribution but not for oral absorption.

Acute Kidney Injury↗
PubMed1990

Indoor firing range air quality: results of a facility design survey.

A survey of 611 indoor firing ranges identified features of range design, operation, and maintenance that could affect air quality, a concern because of the lead composition of ammunition fired at the ranges. Features examined included the number of firing positions, location and type of air-handling equipment, maintenance practices, and other standard operating procedures (SOPs). Analysis of the data from the 339 valid responses showed that these ranges vary widely in design, construction, number of firing positions, and frequency of use. Most of these ranges were constructed years ago to the standards in force at the time. Consequently, they do not include many features specified in current standards. Findings from the survey suggest two possible options for ranges concerned about the lead exposure level: design upgrades and SOP changes. Retrofits are costly and design solutions must rely on existing criteria, many of which need verification to ensure their adequacy. Also, more research is needed to define the relationships between ventilation system design and lead exposures at the firing line. A lower cost, more expedient solution is to establish a program of prevention through changes in SOP, such as prohibition of unjacketed lead bullets or establishment of a regular program to monitor the proper operation of ventilation systems. Technology to enhance these preventive measures is being investigated. Possible products include devices for real-time monitoring of ambient air quality and personal lead dosage monitors. This study has underscored the need for further site studies to verify design criteria and to collect chemical and physical data that will help define the nature and extent of problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗