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B Bolon

Publications and source records attributed to B Bolon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of 2-methoxyethanol on mouse neurulation.

The potent developmental toxicant, 2-methoxyethanol (2-ME), elicits exencephaly in near-term mouse fetuses following a single maternal treatment early on gestation day (gd) 8. Deleterious morphological consequences to the neurulating embryo shortly after exposure have not been reported. The present study was designed to fill this gap and to investigate the impact of 2-ME treatment on cell death patterns in the embryonic neural folds. Dams were injected subcutaneously with saline, 250 or 325 mg 2-ME/kg 2 hr prior to the beginning of gd 8. The effect of 2-ME on gross and microscopic neural development was examined in conceptuses on gd 9, 6 hr (9:6), 10:6, and 18:0. Compared to saline, 2-ME treatment increased the percentage of embryos with open neural tubes (ONTs) at all gestation days. Although few statistically significant differences (P < 0.05) existed among the ONT rates on the 3 observation days, an interesting biological response occurred. Both high and low 2-ME doses appeared to elicit the greatest incidence of neural tube patency on gd 9:6 (affecting approximately 27% of embryos). During the subsequent 24 hr, recovery occurred and many neural folds apparently closed. Consequently, the ONT incidences on gd 10:6 (approximately 11%) were quite similar to the gd 18 exencephaly rates elicited by both chemical treatments (approximately 15%). A dose response was not seen due to a substantial increase in resorption rates following the 325 mg/kg dose. Compared to the other treatment groups, the low 2-ME dose significantly inhibited embryonic growth as indicated by reduced crown-rump and head lengths and increased incidence of developmentally delayed brain maturation. To evaluate chemically induced changes in cell death, neurulating embryos were collected on gd 8:6 and either immersed in the vital dye, Nile blue sulfate (NBS), or processed for histopathology. In 2-ME-exposed embryos, excessive NBS uptake occurred in neural fold neuroepithelium at sites of nonclosure. Using histopathology, the extent of cell death in the cephalic neural folds was dependent on the 2-ME dose, and the neuroepithelium was more severely affected than the mesenchyme. These observations suggest 1) a trend toward repair and catch-up growth later in gestation which may ameliorate the overt early effects of 2-ME, and 2) an association between enhanced cell death and regions of the neural tube particularly vulnerable to nonclosure.

Animals↗
PubMed1996

Region-specific DNA synthesis in brains of F344 rats following a six-day bromodeoxyuridine infusion.

Prolonged exposure to certain alkylating chemicals induces glial and meningeal tumours in rats, probably resulting from DNA damage to dividing neural cells. The present work evaluated DNA synthesis in the brains of untreated, young adult male F344 rats in order to define a BrdUrd infusion protocol to more adequately assess proliferation in slowly dividing neural cell populations. BrdUrd (2.5 to 160 mg/ml) was administered for 6 days via subcutaneous osmotic pumps. Clinical toxicity was not observed at any dose. The labelling index (LI; % of cells per brain area that incorporated BrdUrd) and unit length labelling index (ULLI; % of cells per meningeal length that incorporated BrdUrd) were calculated for selected regions by counting labelled neural cells in defined areas of the right hemisphere in coronal brain sections. Intensely stained cells were numerous in the cerebral subependymal layer (LI = 35.8%); scattered in cerebral white matter tracts (e.g. corpus callosum and internal capsule; LI = 6.2%) as well as cerebral (ULLI = 4.2%) and cerebellar (ULLI = 3.6%) meninges; and rare in the hippocampus (LI > 0.1%). Mildy stained cells were dispersed in the pons (LI = 2.1%), deep cerebral (LI = 1.8%) and cerebellar (LI = 1.0%) grey matter, and thalamus (LI = 0.3%). Phenotypically, BrdUrd-positive cells in neuropil were glial cell precursors and their progeny, while those associated with meninges were usually located in the superficial subarachnoid space and appeared to be fibrocytes. Using BrdUrd infusion, LI for glial precursors at these sites ranged from two- to 10-fold higher than those reported previously after a brief parenteral pulse dose. These data indicate that continuous BrdUrd infusion for 6 days by subcutaneous osmotic pump is an efficient means of labelling neural cells throughout the brain.

Animals↗
PubMed1995

Role of formate in methanol-induced exencephaly in CD-1 mice.

Mouse embryos develop exencephaly when dams are exposed by inhalation to high concentrations (> or = 10,000 ppm) of methanol on gestational day 8 (GD8; copulation plug = GD0). The present study examined the role of formate, an oxidative metabolite of methanol, in the development of methanol-induced exencephaly in CD-1 mice and cultured mouse embryos. The pharmacokinetics and developmental toxicity of sodium formate (750 mg/kg by gavage), a 6-hr methanol inhalation (10,000 or 15,000 ppm), or methanol gavage (1.5 g/kg) in pregnant CD-1 mice on GD8 were determined. Gross morphological evaluations for neural tube closure status in embryos or exencephaly in near-term fetuses were performed. Decidual swellings and maternal plasma were analyzed for methanol and formate. The mean (+/- S.E.M.) end-of-exposure plasma methanol concentration was 223 +/- 23 mM following the 6-hr, 15,000 ppm methanol inhalation. There were no changes in blood or decidual swelling formate concentrations under any of the methanol exposure conditions. Peak formate levels in plasma (1.05 +/- 0.2 mM; control 0.5 +/- 0.3 mM) and decidual swelling (2.0 +/- 0.2 mM; control 1.1 +/- 0.2 mM) from pregnant mice (GD8) given sodium formate (750 mg/kg, po) were similar to those observed following a 6-hr methanol inhalation of 15,000 ppm (plasma = 0.75 +/- 0.1 mM; decidual swelling = 2.2 +/- 0.3 mM) but did not result in exencephaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Methanol-induced neural tube defects in mice: pathogenesis during neurulation.

A spectrum of cephalic neural tube defects was observed in near-term (gestation day [GD] 17) mouse fetuses following maternal inhalation of methanol at a high concentration (15,000 ppm) for 6 hr/day during neurulation (GD 7-9). Dysraphism, chiefly exencephaly, occurred in 15% of fetuses, usually in association with reduction or absence of multiple bones in the craniofacial skeleton and ocular anomalies (prematurely open eyelids, cataracts, retinal folds). Measurements of cerebrocortical width in grossly normal, methanol-exposed fetuses revealed significant semiquantitative differences in the thicknesses of the frontal cortex and its constituent layers (neuroepithelium, intermediate cortex/subventricular plate, and cortical layer 1) as well as apparent increases in subventricular plate cellularity relative to controls. Subsequently, the early morphogenesis of these neural changes was investigated in neurulating mouse embryos to define tissue-specific patterns of methanol-induced damage that lead to cephalic axial dysraphism. Following daily 6-hr maternal inhalations of 15,000 ppm methanol during GD 7-8, the cephalic neural fold margins were swollen, blunted, and poorly elevated on GD 8.5 and 9 relative to controls. Histopathology of exposed GD 8.5 embryos revealed microcephaly in association with reductions in the cell density and mitotic index of at least 47% in the cranial mesoderm. The mitotic index in the embryonic neuroepithelium was also reduced by 55%, and groups of neural crest cells were displaced to the neural folds dorsal to the foregut (relative to the more ventral location in the facial regions of control embryos). When examined on GD 9.5 and 10.5, maternal methanol exposure (15,000 ppm for 6 hr/day) during GD 7-9 resulted in stunting, delayed rotation, and microcephaly in over 90% of the affected embryos. Persistent patency of the anterior neuropore and prosencephalic hypoplasia were seen in > 40% and up to 90% of embryos, respectively. Shallow optic vesicles, stunted branchial arches, scoliosis, and hydropericardium were also observed. Many 10.5-day-old embryos were edematous. Occult dysraphism, recognized grossly by abnormally narrow cephalic conformation and histopathologically by the absence of mesoderm in the mesencephalon, was present in at least 21% of methanol-exposed embryos on GD 9.5 and 10.5. Nile blue vital dye staining of methanol-exposed embryos revealed no difference in dye accumulation between control and treated embryos on GD 8.5, 9.0, or 9.5. There were no apparent dysmorphogenic effects in control embryos at any stage of development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Lip fibromas associated with retrovirus-like particles in angel fish.

Fibromas were observed on the lips of adult female and juvenile angel fish (Pterophyllum scalare) from 3 Florida farm populations. Tumor prevalence in each population was < 1%. Affected fish were clinically normal except for those with large tumors, which had weight loss caused by physical obstruction of food intake. Fibromas originated as elevated masses from the mucocutaneous junction near the midline of the upper and/or lower lips. Characteristic features included dense fibrous stroma covered by thickened, stratified squamous epithelium, numerous intraneoplastic teeth, and scattered foci of stromal inflammation. Electron microscopy revealed intracytoplasmic type-A retrovirus-like particles in stromal cells from all tumors. Attempts to transmit fibromas, using a cell-free tumor ultrafiltrate, were unsuccessful. The relationship of the intraneoplastic viral particles to the development of lip fibromas in angel fish is uncertain.

Animals↗
PubMed1993

Acute methanol toxicity in minipigs.

The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Average maximum methanol concentrations in plasma, of 3100 +/- 700 (SD), 6200 +/- 2300, and 15,200 +/- 900 micrograms/ml were reached within 0.5 to 4 hr following methanol administration in animals given 1.0, 2.5, or 5.0 g methanol/kg, respectively. The mean initial elimination half-lives of methanol were 9.0 +/- 1.6, 22.4 +/- 6.1, and 18.9 +/- 4.3 hr, for 1, 2.5, and 5.0 g/kg doses, respectively. In 3 minipigs, a transient increase in plasma formate concentration (1.74-3.40 mEq/liter vs control = 0.5 +/- 0.3 mEq/liter) occurred 4 to 30 hr following methanol administration. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuro-ocular toxicosis.

Animals↗
PubMed1993

Phase-specific developmental toxicity in mice following maternal methanol inhalation.

Methanol is toxic to embryos of mice and rats when inhaled by dams at high concentrations. The present studies examined methanol-induced developmental toxicity following inhalation exposure (6 hr/day) of pregnant CD-1 mice to 5000, 10,000 or 15,000 ppm either throughout organogenesis (GD 6-15), during the period of neural tube development and closure (GD 7-9), or during a time of potential neural tube reopening (GD 9-11). Transient neurologic signs and reduced body weights were observed in up to 20% of dams exposed to 15,000 ppm. Examination of near-term fetuses revealed embryotoxicity (increased resorptions, reduced fetal weights, and/or fetal malformations) at 10,000 and 15,000 ppm, while 3-day exposures at 5000 ppm yielded no observable adverse effects. Terata included neural and ocular defects, cleft palate, hydronephrosis, deformed tails, and limb (paw and digit) anomalies. Neural tube defects and ocular lesions occurred after methanol inhalation between GD 7-9, while limb anomalies were induced only during GD 9-11; cleft palate and hydronephrosis were observed after exposure during either period. These findings were consistent with prior reports that maternal methanol inhalation at high levels induces developmental toxicity in a concentration-dependent manner. Furthermore, our data indicate that the spectrum of teratogenic effects depended upon both the timing (i.e., stage of embryonic development) and the number of methanol exposures.

Abnormalities, Drug-Induced↗
PubMed1993

The toxic effects of formate in dissociated primary mouse neural cell cultures.

Primary dissociated mouse cerebrocortical cell cultures containing both neurons and glial cells were used as an experimental model to study the neurotoxic effects of formate, the putative toxic metabolite of methanol. Neural cells were isolated and prepared from the cerebral cortex of fetal CD-1 mice on Gestational Day 15. Mature 7- to 15-day-old monolayer cultures were exposed to formate (0 to 240 mM) for 8 hr at 37 degrees C over a range of extracellular pH (6.0 to 7.6). Cytotoxicity was evaluated by histopathology, changes in membrane integrity (lactate dehydrogenase release, LDH; [14C]adenine nucleotide leakage), and mitochondrial metabolic activity [reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT]. Similar quantitative estimates of cell injury were obtained by LDH release or [14C]adenine nucleotide leakage from prelabeled cells. Exposure of neural cells produced time- and concentration-dependent toxic responses. The concentration of formate that resulted in 50% LDH leakage after an 8-hr incubation was estimated to be 45 mM. As determined by light microscopy, formate (20 to 60 mM) was specifically neuronotoxic, primarily affecting large polygonal neurons. Higher concentrations of formate (> or = 120 mM) induced nonspecific cytotoxicity. MTT reduction appeared to be a more sensitive endpoint by showing significant toxic effects at 20 mM (8-hr incubation), while significant leakage of LDH occurred only at formate concentrations > or = 60 mM. Total intracellular ATP concentration was significantly decreased following a 20 or 40 mM formate exposure for 8 hr. These results are consistent with the hypothesis that formate may inhibit mitochondrial function resulting in decreased intracellular ATP and formate-induced neurotoxicity.

Adenine Nucleotides↗
PubMed1993

An epizootic of Edwardsiella tarda in largemouth bass (Micropterus salmoides).

Edwardsiella tarda, an opportunistic bacterial pathogen, was isolated from dying largemouth bass (Micropterus salmoides) during an epizootic in a eutrophic lake system, Lochloosa Lake, Florida, USA. Approximately 1,500 adult fish died over a 6-wk period during the late summer and early fall of 1991. A mixed population of aerobic bacteria (E. tarda, Aeromonas hydrophila, and Pseudomonas sp.) was isolated from deep cutaneous ulcers and intestines of moribund bass. However, E. tarda in pure culture was the only bacterium isolated from several viscera of several fish; E. tarda may be the etiologic agent responsible for some episodes of seasonal mortality in largemouth bass.

Animals↗
PubMed1992

Biochemical correlates for behavioral deficits induced by secalonic acid D in developing mice.

Humoral signals (neurotransmitters and hormones) control cell division, migration, and differentiation processes which define the organization of brain pathways. Alterations in maternal, fetal, and neonatal biochemistry during critical periods of neurogenesis may irreparably alter the circuitry and, thus, postnatal behavior of young animals. Secalonic acid D (SAD), an ergochrome mycotoxin, causes behavioral and neurochemical deficits in developing mice following prenatal (transplacental) or early postnatal (transmammary) exposure. SAD-induced functional abnormalities include delays in reflex behaviors, integrated neuromuscular activity and strength, stress adaptation responses, and sensory discrimination. These behavioral changes are associated with reductions of brain monoamine neurotransmitter levels in both fetuses and neonates. SAD also alters concentrations of maternal plasma corticosteroids and fetal cyclic nucleotides during midgestation. SAD thus modulates several chemicals in pregnant mice and their fetuses which contribute to brain development, suggesting that this mycotoxin may pose a neuroteratogenic hazard to other immature mammals, including human infants.

Animals↗
PubMed1992

Systemic toxicosis associated with azathioprine administration in domestic cats.

Five cats were treated with an azathioprine suspension (2.2 mg/kg of body weight on alternate days) and 2 cats were given vehicle (controls) for 9 weeks. Complete blood and platelet counts and serum biochemistry variables were monitored weekly. Bone marrow aspirates were evaluated every 3 weeks, and core bone marrow biopsy was performed at the end of the study. Profound neutropenia (less than 600 cells/microliters) was observed in all treated cats, and 1 cat developed pancytopenia. Treatment was discontinued if the WBC count was less than 3,000 cells/microliters. Four weeks after discontinuation of azathioprine, 1 treated cat again was given azathioprine at a lower dosage (1.1 mg of azathioprine/kg on alternate days) and neutropenia recurred within 2 weeks. During treatment, 3 cats developed thrombocytosis, and 2 developed thrombocytopenia. In 4 of 5 cats, neutropenia and thrombocytopenia resolved when azathioprine was discontinued. Bone marrow cytologic examination during treatment revealed reduction of the neutrophil line, with relative increase in monocytes. Core bone marrow biopsy at the completion of the study revealed hypocellular marrow with marked decrease in the myeloid series in cats given azathioprine. One of the cats that was treated with azathioprine had a hypercellular marrow with increased numbers of mature granulocytes and precursors; however, azathioprine had been discontinued 3 weeks prior to biopsy. Alterations in serum biochemical variables were not associated with azathioprine. Two cats that were treated with azathioprine developed respiratory tract infections, and 1 of them was euthanatized during the study.

Animals↗
PubMed1991

Functional deficits produced by 3-methylindole-induced olfactory mucosal damage revealed by a simple olfactory learning task.

Methods for assessing functional consequences of olfactory mucosal damage were examined in rats exposed to 3-methylindole (3-MI). Treatment with 3-MI (400 mg/kg) induced severe degeneration of olfactory sensory epithelium followed by regeneration, fibrous adhesions, and osseous remodeling of the nasal passages. At 100 mg/kg, there was mild Bowman's gland hypertrophy while the sensory epithelium remained intact. Rats receiving 3-MI demonstrated a treatment-related deficit in acquiring an olfactory learning task which was not due to altered cognitive abilities, as determined by subsequent testing in a step-through passive avoidance task. The results confirm the conclusion that alterations in functional indices resulted from 3-MI-induced anosmia and demonstrate the utility of simple learning tasks in assessing functional capacity following olfactory epithelial damage in rats.

Animals↗
PubMed1991

Toxic interactions in the rat nose: pollutants from soiled bedding and methyl bromide.

Interactions between test chemicals and pollutants can confound toxicology studies. To test the sensitivity of the regenerating olfactory epithelium to additional challenge with the olfactory epithelial toxicant methyl bromide (MeBr), Fischer 344 (F344) rats received 2 6-hr inhalation exposures (separated by a 28-day recovery period) to either 0 or 175 ppm MeBr. The regenerating epithelium was resistant to the second MeBr exposure. In addition, histopathologic examination revealed squamous epithelial hyperplasia in the vestibule; inflammation, epithelial necrosis, mucosal erosions, and squamous metaplasia of the respiratory epithelium in the anterior nose; and olfactory sensory cell loss in the dorsal medial meatus. These changes could not be attributed to MeBr, but they were correlated with housing in filter-capped cages between MeBr exposures and were presumably caused by volatile pollutants from soiled bedding. Moreover, olfactory sensory cell loss in the dorsal medial meatus was associated with local resistance to MeBr-induced damage in rats with pollutant-induced changes. Analysis of cage air revealed a progressive increase in ammonia levels between bedding changes (up to 50 ppm), but exposure to 300 ppm ammonia in an additional experiment reproduced only the anterior nasal lesions and not olfactory sensory cell loss. This study demonstrates that 1) regenerating olfactory epithelium is refractory to further MeBr toxicity; 2) pollutants from soiled bedding (in addition to ammonia) produce nasal lesions; and 3) pollutant-induced changes modify the nasal response to inhaled MeBr.

Administration, Inhalation↗
PubMed1990

Systemic amyloidosis in a mare.

A mare with chronic cachexia had multiple skin nodules, abdominal masses (attached and free floating), and large lymph nodes. Fine-needle aspiration cytologic evaluation of a skin mass revealed multinucleated giant cells surrounding eosinophilic material. Histologic evaluation revealed extensive amyloid deposits within the masses, lymph nodes, and the interstitium of many organs. The presence of systemic (visceral) and organ-limited (cutaneous) forms of amyloid is rare in horses. Amyloid congophilia was retained after potassium permanganate oxidation. The fibrils were thus distinct from the AA (secondary) fibrils that are found in most cases of equine amyloidosis, suggesting that this mare may have had primary amyloidosis. Regardless of fibril type, the presence of multinucleated giant cells in association with eosinophilic material in cytologic preparations of skin nodules may suggest a differential diagnosis of amyloidosis in horses.

Amyloidosis↗
PubMed1990

Characteristics of canine melanomas and comparison of histology and DNA ploidy to their biologic behavior.

The biologic behavior of 179 formalin-fixed, paraffin-embedded canine melanomas was correlated with their histologic appearance. In addition, flow cytometric analysis of DNA content was performed on 54 of these tumors. Histologic examination accurately predicted clinical course in 89% of the melanomas with known behavior. Flow cytometry accurately predicted behavior in 93% of tumors with diagnostic histograms and demonstrated malignant features in 100% of metastases from malignant oral tumors; histograms were non-diagnostic for 15% of tumors tested. Histologic examination, flow cytometry, and biologic behavior were in agreement for 93% of the tumors with diagnostic histograms. Interpretive problems were encountered in analyzing heavily pigmented melanomas using this flow cytometry technique.

Age Factors↗
PubMed1989

Behavioral and developmental effects in suckling mice following maternal exposure to the mycotoxin secalonic acid D.

Pregnant mice (dams) were gavaged once on gestational day 13 with 4 ml/kg of dimethylsulfoxide vehicle containing 0 (groups 15, 25 and negative control) or 25 (positive behavioral teratogenic control group) mg/kg of secalonic acid D (SAD). While nursing their offspring, dams were gavaged on postgestational days 1 to 10 with vehicle containing 0 (negative and positive control groups), 15 (group 15) or 25 (group 25) mg/kg/day of SAD. Gestational lengths, maternal pregnancy weights, litter sizes, neonatal sex ratios, neonatal physical appearance and female birth weights were unaffected by prenatal treatment, but male pups born to positive control dams weighed less (p less than 0.05) than negative control group. Compared to negative control, the positive control dams gained significantly more weight while nursing their offspring. Prenatal (positive control) and postnatal (15, 25) SAD exposure delayed ontogeny of surface righting, olfactory discrimination and hindlimb grip behaviors in males and females, and testes descent in males. Negative geotaxis in male and female offspring of group 25 and male offspring of positive control group, as well as times of incisor eruptions of both sexes in groups 15 and 25 were delayed. A significant dose-response effect in olfactory discrimination existed between the groups exposed to postnatal SAD. SAD was behaviorally teratogenic following both prenatal and early postnatal exposure.

Animals↗