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Biomedical subjects

L L Hall

Publications and source records attributed to L L Hall.

63 records · Page 4Linked to original sources
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Potential developmental toxicity of anatoxin-a, a cyanobacterial toxin.

Some 2000 species of cyanobacteria (blue-green algae) occur globally in aquatic habitats. They are able to survive under a wide range of environmental conditions and some produce potent toxins. Toxin production is correlated with periods of rapid growth (blooms) and 25%-70% of blooms may be toxic. Anatoxin-a is an alkaloid neurotoxin that acts as a potent neuro-muscular blocking agent at the nicotinic receptor. Acute toxicity, following consumption of contaminated water, is characterized by rapid onset of paralysis, tremors, convulsions and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The current studies were conducted to examine the effect of in utero exposure on postnatal viability, growth and neurodevelopment, to evaluate the potential of in vitro embryotoxicity, and to explore the synergistic relationship between anatoxin-a and the algal toxin microcystin-LR by the oral route. The results of preliminary studies on amphibian toxicity are also reported. Time-pregnant mice received 125 or 200 microg kg(-1) anatoxin-a by intraperitoneal injection on gestation days (GD) 8-12 or 13-17. Pup viability and weight were monitored over a 6-day period. Maternal toxicity (decreased motor activity) was observed at 200 microg kg(-1) in both treatment periods. There were no significant treatment-related effects on pup viability or weight on postnatal day (PND) 1 or 6. The GD 13-17 pups were evaluated on PND 6, 12 and 20 for standard markers of neurodevelopmental maturation (righting reflex, negative geotaxis and hanging grip time). No significant postnatal neurotoxicity was observed. In vitro developmental toxicity was evaluated in GD 8 mouse embryos exposed to 0.1-25 microm anatoxin-a for 26-28 h. Perturbations in mouse yolk sac vasculature were noted from the 1.0 microm concentration in the absence of significant embryonic dysmorphology. Potential algal toxin synergism was tested in mice receiving either 0, 500 or 1,000 microg kg(-1) microcystin-LR by gavage and approximately 50 min later receiving either 0, 500, 1,000 or 2,500 microg kg(-1) anatoxin-a by the same route. No deaths occurred at any dose and no definitive signs of intoxication were observed. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg l(-1) of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient narcosis, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure. The observed delay between initial exposure and death is highly unusual for anatoxin-a.

Animals↗
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Lack of teratogenicity of microcystin-LR in the mouse and toad.

Microcystin-LR (MC-LR) is a cyanobacterial toxin generated by the organism Microcystis aeruginosa. Although the hepatotoxicity of this chemical has been characterized, the potential developmental toxicity in vertebrates has not been well studied. The purpose of this study was to elucidate the effects of this toxin on the in vivo and in vitro development of mammals and the development of an Anuran (toad). Initial acute toxicity experiments with female CD-1 mice were accomplished with MC-LR administered i.p. in saline. Lethality occurred at 128 and 160 microg kg (-1) and histopathology revealed massive hepatic necrosis with diffuse hemorrhage. Developmental toxicity studies were done with MC-LR administered i.p. for 2-day periods: gestation days 7-8, 9-10 or 11-12. Doses used ranged from 2 to 128 microg kg(-1). On gestation day 17, fetuses were weighed and analyzed for gross morphological and skeletal defects. No treatment-related differences were seen in litter size, viability, weight or the incidence of anomalies. Groups of dams dosed with 32-128 microg kg(-1) on gestation days 7-8, 9-10 or 11-12 were allowed to give birth and the growth and development of their pups were followed postnatally. There were no significant effects noted in the offspring of the treated dams. Neurulation-staged CD-1 mouse conceptuses were exposed to 50-1000 nM MC-LR in whole embryo culture for 24 h. No significant increase in abnormalities or developmental delays was observed. Finally, exposure of the developing toad. Bufo arenarum was done from stage 17 (tail bud) for 10 days at concentrations of 1-20 mg l(-1). No effect on morphological development or survival was noted in any exposed groups. These data indicate that microcystin does not appear to affect development adversely in the mouse (in vivo or in vitro) or the toad at the doses and exposure parameters used.

Animals↗
PubMedDate not supplied

Generation and characterization of antibodies against synthetic peptides of porcine zona pellucida ZP3 alpha.

OBJECTIVE: Use of synthetic zona peptides as target immunogens is a promising approach to an anti-fertility vaccine. To elucidate contraceptive epitopes, we raised polyclonal antibodies against synthetic peptides of pig ZP3 alpha and evaluated for immunogenicity, ability to inhibit in vitro boar sperm-pig zona attachment, and cross-reactivity with human zonae. METHODS: Five synthetic peptides were chosen based on hydropathicity analysis of ZP3 alpha, synthesized and coupled to keyhold limpet haemocyanin (KLH). Pairs of male rabbits were immunized with each peptide-KLH conjugate using a multi-site intradermal injection protocol. Resulting antisera were evaluated for immunoreactivity with cognate peptide and ZP3 alpha/EBGD (purified endo-beta-galactosidase-digested ZP3 alpha), contraceptive potential using an in vitro pig gamete bioassay, and cross-reactivity with human zonae using indirect immunofluorescence. RESULTS: All anti-peptide-KLH sera demonstrated immunoreactivity with cognate peptide. Anti-peptide sera, except for anti-alpha-3-KLH serum, were less immunoreactive with ZP3 alpha/ EBGD. Antisera directed against alpha-1-KLH, alpha-2-KLH, and alpha-3-KLH demonstrated significant (P < .00001) inhibition of boar sperm-pig zona attachment. Only anti-alpha-2-KLH and anti-alpha-3-KLH sera cross-reacted with human zonae. CONCLUSION: Synthetic peptides of pig ZP3 alpha are immunogenic, elicit antibodies cross-reactive with human zonae, and have in vitro contraceptive activity. These data support continued investigation of synthetic ZP3 alpha peptides as potential target immunogens for anti-fertility vaccine development.

Amino Acid Sequence↗