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D J Schaeffer

Publications and source records attributed to D J Schaeffer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Phototoxicology. 2. Near-ultraviolet light enhancement of Microtox assays of trinitrotoluene and aminodinitrotoluenes.

Coexposure of 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2A), or 4-amino-2,6-dinitrotoluene (4A) to near-ultraviolet (nuv) light (lambda max-354 nm) significantly enhanced their toxicity toward Photobacterium phosphoreum (Microtox bioassay) during 30 min but not 15 min. Based on the slopes of the dose-response lines, the nuv coexposure and dark toxic mechanisms of action for TNT, 2A, and 4A appeared to be similar. nuv coexposure of binary mixtures significantly enhanced (supraadditivity) the toxicity of these compounds to P. phosphoreum. Under normal laboratory lighting, the toxicity of TNT + 2A and 2A + 4A mixtures were supraadditive but the toxicity of TNT + 4A mixtures could be explained by simple addition. Supporting these conclusions, the response curves of alpha-terthienyl, a compound known not to require nuv for toxicity, were similar in the dark and with nuv coexposure. In contrast, angelicin and psoralen, compounds known to require nuv coexposure to damage DNA, gave response curves having different slopes in the dark and with nuv coexposure. The nuv coexposure Microtox assay was able to detect and quantify phototoxicity in psoralen, angelicin, alpha-terthienyl, anthracene, TNT, and aminodinitrotoluenes.

Aniline Compounds↗
PubMed1994

Phototoxicology. 3. Comparative toxicity of trinitrotoluene and aminodinitrotoluenes to Daphnia magna, Dugesia dorotocephala, and sheep erythrocytes.

2,4,6-Trinitrotoluene (TNT) and compounds associated with its production are toxic and phototoxic to a wide range of biota. The planarian Dugesia dorotocephala, but not Daphnia magna, metabolized TNT (1 mg/liter) to 4-amino-2,6-dinitrotoluene (4A; 0.4 mg/liter) and 2-amino-4,6-dinitrotoluene (2A; 0.2 mg/liter). Coexposure to near-ultraviolet (nuv) light enhanced the toxicity of 2A more than that of TNT and 4A. The toxicities of TNT, 4A, and 2A to Du. dorotocephala were all decreased by glutathione (GSH) conjugation. This suggests that all had mechanisms of toxic action involving formation of quinone-GSH conjugates. Dark and light mechanisms for TNT and 2A depended on GSH conjugation, but the specific mechanisms may be different for each compound. The dark and light mechanisms of toxic action for 4A appeared to be fundamentally different in that the dark toxic mechanism of action was less dependent on GSH conjugation. Hemolysis studies using sheep erythrocytes showed that the light-enhanced toxic mechanism of action for TNT, 2A, and/or 4A did not involve cellular membrane damage in response to nuv-induced anions.

Abnormalities, Drug-Induced↗
PubMed1994

Temporal and dose-response features in swine fed corn screenings contaminated with fumonisin mycotoxins.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme and F. proliferatum, induces liver damage and pulmonary edema in swine. We examined the temporal and dose-response features of FB1 toxicosis in male weanling crossbred pigs fed nutritionally balanced diets, containing corn screenings naturally contaminated with fumonisins, for 14 days. Total fumonisins (FB1 and FB2) in diets 1 through 6 were assayed at 175, 101, 39, 23, 5, and < 1 ppm (below detectable concentrations), respectively. Clinical signs, serum biochemical alterations, and morphologic changes were evaluated. Pigs were weighed, and bled for hematologic and clinical chemistry evaluation on days 5 and 14. They were euthanized on day 14, or earlier if respiratory distress was observed. Respiratory distress developed in 3/5 pigs fed diet 1 between days 4 and 6 due to severe pulmonary edema and pleural effusion. Histologic evidence of hepatic injury was present in all pigs fed diets 1 and 2, 3/5 on diet 3, and 1/5 on diet 4. Serum bilirubin and cholesterol concentrations, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and arginase (ARG) activities were elevated in pigs fed diets 1 and 2. Based on liver histopathology, the no observed adverse effect level (NOAEL) for fumonisin toxicity in swine was < 23 ppm total fumosins for the 14-day period. Based on regression analyses of the clinical chemistry profiles at 14 days, the NOAEL was < 12 ppm, with ALP being the most sensitive parameter. In conclusion, pulmonary edema occurred only at the highest fumonisin concentration (175 ppm), while liver damage occurred at much lower concentrations with a NOAEL of < 12 ppm.

Animal Feed↗
PubMed1994

Three-dimensional kinematics of the intact and cranial cruciate ligament-deficient stifle of dogs.

Joint motion was measured for the intact and cranial cruciate ligament (CCL)-deficient stifle in five large dogs using an instrumental spatial linkage and radiophotogrammetry. The linkage was directly attached to the bones using modified bone plates. Motion data were presented in terms of a clinical coordinate system. Stifle kinematics were highly reproducible for a given dog. For intact stifle kinematics, the swing phase included flexion-extension, internal-external rotation and abduction-adduction, while stance-phase kinematics included only flexion-extension. Loss of the CCL altered joint kinematics over the entire gait cycle. At the swing-stance transition, the CCL-deficient stifle demonstrated an abrupt cranial subluxation of the tibia which was sustained throughout stance. At the beginning of the swing phase the CCL-deficient joint returned to the cranial-caudal alignment seen in the intact joint. The dog's stifle was shown to be CCL-dependent during stance. The dog compensated for CCL loss by reducing the external limb load and by carrying the limb in greater flexion throughout the gait cycle, but was unable to prevent joint subluxation during stance. Stifle kinematics are greatly altered following CCL loss. It is the repetitive, mechanical, dynamic subluxation in a CCL-deficient joint which may be the cause of joint degeneration.

Animals↗
PubMed1994

Growth and ovarian function of weanling and yearling beef heifers grazing endophyte-infected tall fescue pastures.

Growth and ovarian function of crossbred beef heifers grazing low and high endophyte-infected tall fescue pastures were studied for 2 successive years. In April of each year, 20 weanling and 20 yearling heifers were included in the study. All heifers were weighed at 28-d intervals for 112 d. Blood samples were collected from each heifer on Day 0 and +7 of each of five 28-d periods and analyzed for progesterone concentration. Heifers with progesterone concentrations >/= 1.5 ng/ml on either or both Day 0 and +7 were classified as having normal cyclic ovaries. High endophyte-infected fescue pastures adversely altered the ovarian activity (P < 0.05) of weanling heifers in both years. In each trial, average weight gains were lower (P < 0.05) in yearling and weanling heifers grazing the high endophyte-infected pastures than in heifers grazing low endophyte-infected pastures. In 1992, heifers were synchronized with PGF(2alpha) administered on Days 101 and 112. Blood samples were collected on 0, 4, 8 and 12 d after the second PGF(2alpha) injection for progesterone analysis. Heifers grazing high and low endophyte-infected pastures were pastured separately with 4 bulls each and were given heatmount detectors. At 96 h, less estrus activity was observed (P < 0.10; power=0.63) in weanling heifers grazing the high vs. low endophyte pastures although pregnancy rates were similar for all groups. Progesterone concentrations suggested that weanling heifers on the high endophyte pastures had a higher incidence of luteal dysfunction after PGF(2alpha) synchronization. In summary, high endophyte-infected pastures decreased growth in both weanling and yearling heifers, ovarian activity and luteal function were adversely altered in weanling heifers with subsequent decreased estrus response to estrus synchronization.

Journal Article↗
PubMed1994

Effect of inhibiting 5 alpha-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep.

The extent to which inhibitory effects of testosterone (T) on LH secretion in the ram are mediated by its metabolite dihydrotestosterone (DHT) is unknown. Our objective was to determine the effect of inhibiting 5 alpha-reductase activity on pulsatile patterns of LH release in castrated, T-treated male sheep. Nine Dorset and six Hampshire castrated male sheep were allocated equally to one of three treatment groups: 1) infusion of T (768 micrograms/kg/day), 2) infusion of the reductase inhibitor (RI) L-651,723 (0.6 mg/kg/day), and 3) T+RI infusion. Treatments were continuously infused for 3 days. Blood samples were collected via an indwelling jugular catheter at 10-min intervals for 4 h immediately prior to (Day 0) and during the final 4 h of infusion (Day 3). Changes in mean LH, LH pulse amplitude, LH interpulse interval (IPI), T, 17 beta-estradiol (E), and DHT were derived for each animal by subtracting values for Day 0 from Day 3. Data were subjected to one-way analysis of variance. The increase in T and E after infusion of T was similar (p > 0.10) in T- and T+RI-treated males and greater (p < 0.01) than in RI-treated males. The increase of DHT was greater (p < 0.01) in T-treated than either T+RI- or RI-treated males whereas the change was similar (p > 0.10) for T+RI- and RI-treated males. T decreased mean LH more (p < 0.01) than RI. T+RI suppressed mean LH more (p < 0.01) than RI but not as much (p < 0.01) as T alone.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1994

UV-A coexposure enhances the toxicity of aromatic hydrocarbons, munitions, and metals to Photobacterium phosphoreum.

Johnson et al. (1993) showed that coexposure to UV-A between 300-400 nm enhanced the toxicity of nitrotoluenes to Photobacterium phosphoreum, a marine bioluminescent bacteria used in the Microtox test (Microbics Inc.). This paper reports that UV-A photoenhanced the toxicity of polynuclear aromatic hydrocarbons, other types of organic compounds, and some transition metals to P. phosphoreum. Coexposure to 400 muw/cm2 for 15 min increased the toxicity of psoralen, alpha-terthienyl, anthracene, acridine, fluoranthene, TNT, Cu2-, As3-, Ni2, and Cd2+. Phenanthrene was photoenhanced after 30 min coexposure at 400 muw/cm2-, and Mn2+ at 800 muw/cm2 after 15 min. Naphthalene was not enhanced at 800 muw/cm2 for 30 min.

Metals↗
PubMed1994

Reversion of bioluminescent bacteria (Mutatox) to their luminescent state upon exposure to organic compounds, munitions, and metal salts.

Mutatox is a new genotoxicity bioassay which uses as the endpoint the bioluminescence produced on reversion of a dark strain of the marine bacterium Vibrio fischeri +/- S9. Reversion can occur by several mechanisms, including base substitution, frame-shift, SOS induction, and DNA intercalation. For screening, Mutatox provides many advantages over the Salmonella typhimurium (Ames) assay: it requires minimal sterility, employs a shorter incubation period, and does not require culture maintenance. Eighteen organic chemicals (phenol, polynuclear aromatic hydrocarbons, nitrotoluenes, others), Na3PO4, and 4 genotoxic metals (Cu2+, Ni2+, As3+, Cd2+) were tested. Most of the organic compounds positive in S. typhimurium assays were positive in Mutatox. None of the metals was genotoxic in V. fischeri, possibly due to poor uptake from the saline medium.

Luminescent Measurements↗
PubMed1994

Hepatic total 3 alpha-hydroxy bile acids concentration and enzyme activities in prednisone-treated dogs.

High serum alkaline phosphatase (ALP) activity is considered a sensitive marker of cholestasis in most mammalian species, including dogs. Induction of high serum ALP activity in association with cholestasis is dependent on high hepatic bile acids concentrations. Treatment of dogs with glucocorticoids also results in high serum ALP activity. The possible causal relation between serum ALP activity and bile acids concentration was investigated in dogs treated with glucocorticoids. The relation of glucocorticoid treatment to changes in the activity of individual ALP isoenzymes, alanine transaminase (ALT) and gamma-glutamyltransferase (GGT) also was investigated. Eight conditioned dogs were given 4 mg of prednisone/kg of body weight, i.m., daily for 10 days. Blood samples were taken prior to treatment and on treatment days 3, 5, 7, and 10. Liver tissue was then taken from each dog. Serum total ALP activity was significantly (P < 0.05) high at day 3 in prednisone-treated dogs. Isoenzyme analysis indicated that this increase was attributable to an increase in the liver ALP isoenzyme (LALP). Significant increases in serum corticosteroid-induced ALP (CALP) and bone ALP were first observed on days 7 and 10, respectively. Serum ALT and GGT activities were significantly increased by day 5. Increased serum or hepatic tissue bile acids concentrations were not observed in prednisone-treated dogs, compared with values in 8 clinically normal (control) dogs, but were high in 3 dogs with complete bile duct ligation. Hepatic activities of LALP, CALP, and GGT were higher in prednisone-treated dogs than values in controls, indicating probable increased hepatic synthesis of these enzymes. Hepatic ALT activity was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1994

Evaluation of topically administered tissue plasminogen activator for intraocular fibrinolysis in dogs.

Fibrin clots were induced in eyes of dogs by injection of autogenous citrated plasma into the anterior chamber. Twenty-four hours after clot formation, one 50-microliters drop of tissue plasminogen activator at a concentration of 5 mg/ml (group 1, n = 7) was administered topically 9 times at 5-minute intervals, or a collagen shield that was hydrated with tissue plasminogen activator at a concentration of 5 mg/ml (group 2, n = 7) was applied. The contralateral eye served as a nontreated control. Serial photographs were taken of the fibrin clots after topical application of tissue plasminogen activator. Computerized morphometric analysis was then used to evaluate changes in cross-sectional surface area of the fibrin clot. There was no significant mean percentage decrease in clot surface area of treated eyes of group-1 dogs or in treated eyes of group-2 dogs. In addition, there was no significant difference in mean percentage decrease in clot surface area between treated eyes of group-1 and group-2 dogs.

Administration, Topical↗
PubMed1993

Planarians as a model system for in vivo tumorigenesis studies.

Planarians can be used to devise whole-animal invertebrate bioassays for screening and as an adjunct to, or replacement for, mammalian tests. This paper proposes using planarians for in vivo tumorigenicity studies of pure compounds and complex environmental mixtures, and for mechanistic studies of tumorigenesis. To accomplish the first two stages of the bioassay validation process described by Balls et al. (1990, ATLA 18, 313-337), the literature on tumorigenicity tests with intact planarians is reviewed. Thirteen of 14 mammalian chemical carcinogens produced tumors (usually of undetermined pathohistology) in planarians. Polychlorinated biphenyls are mammalian carcinogens which are cotumorigens but not complete tumorigens in planaria. Data for other mammalian chemical carcinogens for which the planarian results are incomplete are also presented. Planarian tests using mammalian noncarcinogens, compounds which have not been tested for carcinogenicity in mammals, and radiation are also reviewed. The results indicate that both the specificity and the sensitivity of the planarian tumorigen bioassay are high. Furthermore, first-stage validation data indicate that intact planaria can be used as a developmental toxicity bioassay.

Animals↗
PubMed1993

Comparison of the effects of pulsatile and constant testosterone on the secretion of gonadotropins in the ram.

The objective of the present study was to compare the effectiveness of a pulsatile vs. a constant pattern of testosterone (T) infusion to suppress LH and FSH secretion in wethers. Two separate experiments were conducted. In Exp 1, animals were subjected to each of four different iv infusion regimens for 3 days: 1) constant diluent, 2) constant T (768 micrograms/kg.24 h), 3) pulsatile (one pulse every 4 h) diluent, and 4) pulsatile T (768 micrograms/kg.24 h). Blood samples were collected at 10-min intervals for 4 h both before infusion and during the last 4 h of the infusion. Compared to diluent, T decreased (P < 0.001) mean LH and increased (P < 0.001) LH interpulse interval. The LH interpulse interval was increased more (P < 0.005) by constant T than by pulsatile T. Mean LH was slightly more suppressed (P = 0.052) by constant T than by pulsatile T. LH pulse amplitude did not differ between constant T and pulsatile T. In Exp 2, animals were subjected to each of three different iv infusion regimens for 4 days: 1) constant diluent, 2) constant T (384 micrograms/kg.24 h), and 3) pulsatile (one pulse every 6 h) T (384 micrograms/kg.24 h). Both LH the interpulse interval (P = 0.001) and LH pulse amplitude (P = 0.04) were increased more by constant T than by pulsatile T. Mean LH was suppressed more (P = 0.002) by constant T than by pulsatile T. In both Exp 1 and 2, none of the treatments significantly affected mean FSH. These results indicate that constant T is more effective than pulsatile T in suppressing LH secretion in the ram.

Animals↗
PubMed1993

Morphogenetic action of neurotransmitters on regenerating planarians--a review.

Planarians can be used as invertebrate bioassays to evaluate the role of neurotransmitters on regenerating cells. The influence of the nervous system is crucial to regenerate a normal complete animal. The neurotrophic action of the nervous system has been attributed to the major neurohormones present throughout the animal kingdom. The same type of transmitters found in mammals have been extensively found in many invertebrates, including planarians, but their role in regeneration is unclear. Neurotransmitters and drugs which act on neurohumoral transmission have been used to determine the role of each neurohormone on regenerating planarians. Biochemical and pharmacological mechanisms of neurohormones on regenerative planarians are reviewed, as is their putative role on regeneration. Correlations with the roles of neurotransmitters in the central nervous system of higher organisms are also addressed.

Acetylcholine↗
PubMed1993

Planarians as a model system for in vivo teratogenesis studies.

Planarians are free-living flatworms whose organ systems are capable of carrying out complex metabolic functions similar to those of mammals. The biological similarity of planarians to mammals, and the ease and low cost of culturing planarians in the laboratory, makes them a good in vivo animal for screening and mechanistic studies of acute, chronic, neurobehavioral, reproductive, and developmental toxicology. Because only undifferentiated totipotent stem cells, i.e., neoblasts, are capable of mitosis and differentiation in planarians, all abnormal growths, including tumors, originate from this target cell. This review evaluates planarians for use in developmental toxicology as a screening bioassay for compounds and mixtures, and for mechanistic studies.

Animals↗
PubMed1993

Modification by polychlorinated biphenyls (PCBs) of cadmium induced lesions in the planarian model, Dugesia dorotocephala.

The appearance of abnormal growths on the planarian, Dugesia dorotocephala, in response to cadmium with and without pre-exposure to L-buthionine-R, S-sulfoximine (BSO) and concurrent exposure to the polychlorinated biphenyls (PCBs) Aroclor 1254, PCB 28, PCB 110 or PCB 126 is described. Pigmented rose thorn (PRT) lesions were non-invasive and appeared in response to PCBs. Post-head (PH) lesions developed in up to 100% of the animals within 6-20 days post-dosing, progressed rather rapidly and were highly invasive. Round tail tip (RTT) lesions appeared in lower frequencies within 10-30 days, but progressed extremely rapidly resulting in tail loss within 48 h. We have referred to these types of lesions as "tumors", but they are not necessarily characteristic of vertebrate neoplasms. PCBs interacted with cadmium in a complex way, in some cases increasing total lesions and decreasing time-to-lesion and in other cases having the opposite effects. A three-factor (PCB, PCB dose, Cd dose) nested analysis of variance model was used to determine lesion rates in order to compare PCB potencies as potentiators or antagonists. The Aroclor mixture was always the least potent co-toxicant but appeared to be the most potent antagonist; the coplanar PCB 126 was the most potent co-toxicant. The complex response surfaces and the lack of stoichiometry in dose-response relationships indicate that multiple mechanisms are responsible for PH and RTT lesions in planarians. These results emphasize the complexity of PCB toxicities and suggest further studies to validate the planarian model as a screen for combinations or environmental mixtures which may have altered biological potency in other species.

Animals↗