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C G Rousseaux

Publications and source records attributed to C G Rousseaux.

At least 19 recordsLinked to original sources
PubMed2005

Trouble shooting in toxicopathology.

Toxicopathology, also referred to as toxicologic pathology, can be defined as the study of structural and functional changes in cells, tissues, and organs that are induced by toxicants (such as drugs, industrial and agricultural chemicals), toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and physical agents (such as heat and radiation); the investigation of the mechanisms by which these changes are induced; and the development of risk assessment and risk management policies based on such information. Toxicologic pathology primarily deals with the morphologic or structural effects of the toxicant and the mechanism by which this structural effect is induced. This article highlights some of the problems that toxicologic pathologists may encounter in obtaining and interpreting pathology lesions. By alerting toxicologists to some of these issues, it is hoped that a better understanding of the use and limitations of toxicologic pathology data will occur.

Animals↗
PubMed1994

Congenital defects as a cause of perinatal mortality of beef calves.

Congenital anomalies occur at low levels in beef cattle. Usually, severe defects result in abortion of the calf or return to service. In cases that do reach term, however, some die while others may survive with or without assistance from the manager. Regardless of whether the calf survives, the fact that abnormal development occurred raises questions as to etiology of the defect(s) and its impact on the herd. By defining the defect and using a logical method of assessing the cause, one can assess the impact of that defect on future herd production.

Animals↗
PubMed1992

Oral administration of D-penicillamine causes neonatal mortality without morphological defects in CD-1 mice.

D-Penicillamine (DPA) causes axial skeletal defects in rats and fetal lethality when given as 0.83% and 1.6% of the diet, but its mechanism of action on the axial skeleton is unknown. We have been using submerged fetal CD-1 mouse limb-bud organ cultures to evaluate the mechanisms of teratogenesis in the developing murine limb. Before attempting to evaluate the in vitro effects of DPA, a dose response morphological teratology study was undertaken using CD-1 mice to determine the effects of DPA on the mouse and determine the potential of using the mouse limb-bud assay to investigate the terata produced by DPA. Groups (n = 8) of nulliparous pregnant mice (vaginal plug = day 0 of gestation) were dosed, via oral gavage, with 0, 250, 500, 1000 and 2000 mg kg-1 DPA for the first 12 days of gestation. Body weights and food consumption were measured daily. On day 18, fetuses were removed by Caesarian section. Two-thirds of the fetal skeletons were stained with alcian blue and alizarin red and then cleared and examined for defects. Soft-tissue defects were examined in the remaining one-third using a modification of the Wilson freehand technique. Maternal body weight gains were not different before day 12 of the experiment, but differed in the interval of day 13-18 (P = 0.004). No group differences were noted in male/female ratios, site of implantation, implantation numbers and number of fetuses. Decreased survivability was seen in the 2000 mg kg-1 group. No treatment-related defects were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1992

The effect of a commercial 2,4-D formulation on chemical- and viral-induced tumor production in mice.

Male CD-1 mice were exposed to a commercial formulation of 2,4-dichlorophenoxyacetic acid (2,4-D), the amine derivative, in the drinking water at concentrations ranging from 0 to 0.163% of the formulated product, equivalent to approximately 0-50 mg kg-1 day-1 2,4-D content. The effect of 2,4-D on urethan-induced pulmonary adenoma formation was evaluated following a 105-day exposure. Urethan-induced sleeping times observed following an i.p. injection of urethan (1.5 mg g-1) after 3 weeks of 2,4-D exposure were not altered by 2,4-D, indicating that 2,4-D did not influence urethan elimination. Pulmonary adenoma production, which was evaluated 84 days after urethan injection, was enhanced by 2,4-D exposure but had no effect on tumor size. The effect of 2,4-D on the incidence of spontaneous murine lymphocytic leukemia was evaluated during the 365-day treatment period. Mortality associated with the leukemia virus was not altered by 2,4-D treatment. Exposure to this commercial 2,4-D product at moderately high levels of exposure may modify the development or expression of certain tumors in CD-1 mice. The mechanism of the co-carcinogenic or tumor-promoting activity associated with 2,4-D exposure remains to be determined.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1992

Role of thiamine status in sulphur induced polioencephalomalacia in sheep.

The effects of excess dietary sulphur were studied in sheep supplemented and unsupplemented with thiamine. The diets contained either 0.19 per cent sulphur (LS) or 0.63 per cent sulphur (HS) in combinations with 14 mg kg-1 thiamine (LB1) or 243 mg kg-1 thiamine (HB1). A total of 56 two-month-old lambs were used. Groups consisting of nine, nine, 22 and 16 lambs were fed LS-LB1, LS-HB1, HS-LB1 and HS-HB1 diets, respectively for 14 weeks. Out of 22 lambs fed the HS-LB1 diet, seven lambs developed neurological signs between the third and eighth week of the trial. Two of these lambs died, three that were in extremis were euthanased, and two recovered completely. All clinically affected animals had extensive malacic lesions in the cerebral cortex, midbrain and brainstem. None of the lambs from the LS groups or HS-HB1 group developed clinical signs. Several clinically normal lambs from the HS-LB1 group had necrotic lesions in their brains at gross and microscopic examination. Supplementation with dietary thiamine prevented development of clinical signs, but did not totally prevent development of microscopic brain lesions. Brain thiamine concentration, transketolase activity and thiamine pyrophosphate (TPP) effect were not different (P greater than 0.05) among groups. There was a strong effect (P less than 0.0001) of dietary thiamine supplementation on blood thiamine concentration and TPP effect. Blood thiamine concentration was higher whereas TPP effect was lower in the thiamine supplemented sheep. Blood and tissue thiamine concentrations in sheep exposed to high dietary sulphur did not indicate either systemic or local thiamine deficiency per se. Increased TPP effect in sheep fed the HS-LB1 diet indicated mild to moderate metabolic thiamine deficiency. Thiamine inadequacy may be an effect of an increased requirement for thiamine in animals exposed to excess dietary sulphur.

Animals↗
PubMed1992

Neuropathologic findings in young male rats in a subchronic oral toxicity study using triethyl lead.

This study was undertaken to ascertain the neuropathologic effects of low level exposure of triethyl lead (3EL) to young male rats. Groups of 20 male Sprague-Dawley weanling rats were given 3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) was given at 200 mg/kg body wt/day as a positive control. Animals (five or six) were perfused with glutaraldehyde following barbiturate anesthesia at the termination of the experiment. These animals and the remaining members of the group received a thorough gross and microscopic postmortem examination. Sections of the central, peripheral, and autonomic nervous systems were examined and lesions scored. No lesions were noted in the brain, but randomly distributed light microscopic changes of spinal cord Wallerian degeneration were noted to increase in a dose responsive manner (rho = 0.48; p < 0.01), with 3EL administration. Ultrastructural examination of selected sections of the lumbosacral nerves, revealed lesions characterized by reduced neurofilaments and neurotubules, and irregular lamellated axoplasmic dense bodies in all animals receiving lead. Organolead was only detected in animals receiving 3EL, but lead cations were detected in all lead-treated animals. The brain lead levels of 1.00 mg/kg/day and 200 mg Pb acetate positive control animals were equivalent. As distinctive ultrastructural lesions were seen in all rats treated with 3EL, we suggest that the no observed adverse effect level (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of thiamin on lead metabolism: organ distribution of lead 203.

The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy.

Administration, Oral↗
PubMed1991

The effects of thiamin on lead metabolism: whole body retention of lead-203.

The effects of thiamin on the whole body retention of led were evaluated in CD-1 mice treated intragastrically or intraperitoneally while exposed to a single dose of lead acetate (100 micrograms) containing 100 mu Ci lead-203. They were administered thiamin (25 or 50 mg/kg body wt.), calcium ethylenediamine tetraacetic acid (CaEDTA) (50 mg/kg body wt.) or their combination in pretreatment or posttreatment regimens for 13 days. Both pre- and posttreatment with thiamin reduced the lead retention compared to the untreated lead-exposed mice, although the different patterns of lead retention were observed. The combined pretreatment (thiamin 50 mg/kg and CaEDTA) and the CaEDTA treatment alone reduced the whole body retention of lead most effectively. Thiamin, CaEDTA and the combined treatments decreased the absorption of lead-203 and the biological half-life of retained lead-203 following oral or intraperitoneal lead exposure. The reduced absorption and enhanced excretion of lead associated with thiamin administration may have therapeutic application for the treatment of lead poisoning.

Absorption↗
PubMed1991

Ovine polioencephalomalacia associated with dietary sulphur intake.

Fifty-six female crossbred two-month-old lambs were housed in individual cages, and fed a basic ration of barley (59%), soybean meal (5%), and alfalfa (32%) prepared to meet NRC nutrient requirements. Four percent of the diet contained a standard salt mix to which the factors inorganic sulphur (S) and thiamine (B1) were added. Four treatment groups were used: low sulphur and normal thiamine (0.19% S, 13.7 mg/kg B1) low sulphur and high thiamine (0.19% S, 243 mg/kg B1), high sulphur and normal thiamine (0.63% S, 13.7 mg/kg B1), high sulphur and high thiamine (0.63% S, 243 mg/kg B1). All animals had free access to water and were offered 1 kg/animal/day of diet for 14 weeks, when necropsy was undertaken. Seven lambs fed unsupplemented (normal B1) diets containing added sulphur developed clinical symptoms of polioencephalomalacia (PEM) between the 3rd and 7th week of the trial. Morbidity (P less than 0.013) and mortality (P = 0.08) differences were attributed to S administration. None of the B1 supplemented lambs developed clinical signs of PEM. Body weight and relative organ weights did not differ among treatment groups. Serial sections of all brains were examined grossly and microscopically. Nonparametric statistical analysis revealed sulphur related effects in the cerebrum, midbrain and hindbrain (P less than 0.0001), no thiamine-related effects or interaction between the factors were seen, except in the amygdaloid body. It was concluded that inorganic sulphur was associated with polioencephalomalacia, and that dietary thiamine may decrease the severity of lesions in some affected areas of the central nervous system.

Animal Feed↗
PubMed1991

Effect of ivermectin on the immune response in mice.

To assess the effect of ivermectin on immune function (antibody production), male CD-1 mice were inoculated with an antigen the day after SC administration of ivermectin (0.2 mg/kg of body weight or 20 mg/kg). Responses were evaluated 5 days after inoculation of the antigen. Antibody production against sheep RBC, a T lymphocyte-, macrophage-dependent response, was enhanced by ivermectin treatment (P = 0.00049). In contrast, antibody production against dinitrophenyl-Ficoll, a T lymphocyte-independent, macrophage-dependent response, was not altered by ivermectin treatment. Results indicate that the immunostimulatory properties of ivermectin are associated with altered function of T lymphocytes, in particular, T-helper lymphocytes. The immunomodulating effects of ivermectin may provide an alternative approach for treatment of disease problems involving immunosuppression.

Animals↗
PubMed1990

The effects of thiamin on the tissue distribution of lead.

The effects of thiamin on the tissue distribution of lead were evaluated in Sprague-Dawley rats exposed to 1000 ppm lead acetate in drinking water and treated daily with thiamin (25 or 50 mg kg-1 body weight, i.p.), calcium ethylenediamine tetraacetic acid (50 mg kg-1 body weight, i.p.) or their combination for 8 weeks. The subtoxic dose of lead did not alter weight gains, feed and water consumption during the treatment period. Thiamin decreased the blood (P less than 0.0001), liver (P less than 0.0001) and kidney (P less than 0.0001) concentrations of lead. Thiamin (50 mg kg-1 body weight) reduced the lead concentrations in tissues more effectively than thiamin (25 mg kg-1 body weight). The combined treatment was more effective than the respective individual treatments.

Animals↗
PubMed1990

Toxicologic studies on a novel antineoplastic bis-Mannich base, derived from a conjugated styryl ketone.

A new bis-Mannich base (NC758) derived from a conjugated styryl ketone has demonstrated activities against human and animal tumors, both in vitro and as xenografts in athymic mice. The present study examined the toxicity of this candidate anticancer drug, when administered intraperitoneally by undertaking LD50, acute dose-response and time-response toxicity studies using CD-1 mice following OECD guidelines. An LD50 of 46.9 +/- 1.4 mg/kg (males) and 65.2 +/- 1.5 mg/kg (females) was calculated using the moving averages method. Signs of toxicity included diarrhea, piloerection, and coma. Gross pathologic findings consisted of an acute fibrinous peritonitis in animals surviving 24 hr or more before death. The acute dose-response study revealed anorexia in mice 24 hr after receiving 25 mg/kg NC758 or more, lasting up to 72 hr in the 50 mg/kg treated group. Neutrophils were significantly elevated in the 25 and 50 mg/kg groups in conjunction with the observed acute peritonitis. Treatment (p = 0.0001), sex (p = 0.0008), and treatment/sex interaction (p = 0.0001) effects were seen in the myeloid-erythroid ratio (MER) of bone marrow. Pathologic changes included thymic necrosis (in all treated mice) and intestinal villous atrophy (in mice treated with 25 and 50 mg/kg). In time-response studies, pathological changes disappeared after 14 days, except for the MER which remained abnormal in males. It was concluded that NC758 was corrosive; hence future studies should utilize the intravenous route, or be given intraperitoneally as divided doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1990

Differentiation of lesions caused by mycotoxin T-2 from autolytic morphologic change in CD-1 mice.

Experiments with topically applied T-2 trichothecene mycotoxin were undertaken to determine whether lesions caused by this toxin could be differentiated from autolysis. Two pathologists, who had previously seen lesions caused by T-2 toxin, graded lesions without knowledge of treatment group and stated whether the animal had received the toxin or not. Both pathologists differentiated T-2 toxin-treated mice up to 6 h post-mortem. Failure to distinguish between treated and control mice resulted in false-negative diagnoses only. It was concluded that the diagnosis of trichothecene mycotoxicosis would probably be missed more than 6 h post-mortem.

Animals↗
PubMed1990

The effects of thiamin on the neurophysiological alterations induced by lead.

The neurophysiological and histopathological alterations were evaluated in Sprague-Dawley rats exposed to 1,000 ppm lead in drinking water and treated with thiamin (25 mg/kg or 50 mg/kg bw), calcium ethylenediamine tetraacetic acid (CaEDTA) (50 mg/kg bw) or their combination for 8 weeks. Alterations in the brain-stem auditory evoked responses (BAERs) were observed during the treatment period. Latency periods associated with the BAERs were increased after 4 weeks of lead exposure. The neurophysiological alterations induced by lead exposure were prevented by thiamin or CaEDTA treatment. The latency periods in the lead exposed rats treated with thiamin, CaEDTA or the combined treatment did not increase in a similar fashion, but resembled more closely the latency periods observed in the rats which were not exposed to lead. The higher dose of thiamin (50 mg/kg) was more effective than the lower dose (25 mg/kg) in the comparable treatment groups. Histopathological examination of the animals did not reveal any pathological changes in the brain, although lesions often associated with lead toxicity were observed in the kidney. The severity of the lesions was not influenced by thiamin or CaEDta treatment. The absence of morphological damage in the CNS in the presence of neurophysiological alterations, indicates that functional deficits may be observed prior to histological evidence of pathological damage.

Animals↗
PubMed1990

Effects of high dietary sulfur on brain functions using evoked potentials technique.

Brain stem auditory-evoked response (BAER) is a noninvasive technique used for detecting neurophysiological abnormalities of the brain stem along the auditory pathway. Brain stem auditory-evoked response recordings were obtained from subcutaneous skin electrodes from two control sheep and 22 other sheep fed high sulfur (S) diets with low or high concentration of thiamine (B1), copper (Cu), and molybdenum (Mo). At least four peaks (I,II,III,IV) of varied amplitude were observed in all animals. Neurophysiological abnormalities due to decreased conductivity and/or excitability of nerve fibers along the auditory pathway were found on the BAER recordings of sheep fed high S diet. Abnormalities of peaks and interpeak latencies within BAER recordings were related to histopathological observations of brain stem lesions. Lesions in the areas of the cochlear nuclei and lateral lemniscus were seen in conjunction with altered BAER components. However, abnormalities in BAER recordings and lesions in the brain stem also occurred in the absence of overt clinical signs. Analysis of interpeak latencies between peaks I and IV revealed significant differences among dietary groups. Sheep given diets low in Cu, Mo, and B1 were affected most. Factorial analysis indicated B1 and interactions among Cu, Mo, and B1 as significant factors influencing interpeak latencies.

Animals↗
PubMed1989

Pharmacology of HI-6, an H-series oxime.

HI-6 is an oxime experimentally developed for reactivation of previously untreatable soman-phosphorylated acetylcholinesterase. It has been shown to be effective in restoring acetylcholinesterase activity after poisoning with other "nerve agents" namely VX and sarin; however, its antidotal qualities for the treatment of organophosphorus pesticide poisoning are not well known. HI-6, and other H-series oximes, apparently act in a number of ways: reactivation of acetylcholinesterase, blockage of ganglia and muscarinic receptors, stimulation of vasopressor and respiratory centre receptors, chemical combination with agents, restoration of neuromuscular transmission, retardation of the formation of the aged inhibitor-enzyme complex, and (or) inhibition of the release of acetylcholine.

Animals↗