Biomedical subjects

Robert L Rogers

Publications and source records attributed to Robert L Rogers.

9 recordsLinked to original sources

PubMed2004

Effect of methoxychlor on various life stages of Xenopus laevis.

The toxicological effects of the organochlorine pesticide methoxychlor were evaluated at various life stages of the South African clawed frog, Xenopus laevis, in an effort to determine stage-specific sensitivity. A battery of four separate assays, including a short-term (4-day) early embryo-larval assay (FETAX) (NF stages 8-46 [Nieuwkoop and Faber, 1994]), 30-day hind limb development assay (NF stages 8-54), 18-day metamorphic climax assay (NF stages 58-66), and 30-day adult reproduction assay were performed. Test concentrations for the FETAX, hind limb development, metamorphic climax, and reproductive assays ranged from 0.0001-1.0 mg/l, 0.0001-0.1 mg/l, 0.0001-0.1 mg/l, and 0.001-0.1 mg/l, respectively. Results from the short-term embryo-larval assay indicated that increased embryo-lethality, malformation, and growth inhibition were not induced at </=1.0 mg/l methoxychlor (maximum soluble concentration). The 30-day hind limb development studies indicated methoxychlor exposure >/=0.01 mg/l delayed hind limb digit differentiation. Follicular hyperplasia of the thyroid glands was noted in specimens exposed to 0.1 mg/l methoxychlor. Results from the 18-day metamorphic climax assay indicated that methoxychlor inhibited the rate of tail resorption in a concentration-dependent manner. Whole body tissue triiodothyronine (T(3)) profiles showed a reduced and delayed surge during climax compared to controls. For the reproductive assessment, adult female X. laevis were super-ovulated and both female and male were then exposed to varying concentrations of methoxychlor. A concentration-dependent reduction in ovary weight and the number of viable oocytes was observed. In exposed male specimens, a concentration-dependent reduction in testis weight and sperm count was found. Methoxychlor was found to accumulate in the ovary, and to a lesser extent in the testis. Based on breeding studies in which exposed females were bred with control males and exposed males bred with control females, the frequency of amplexus, fertilization, and embryo viability was also affected by adult female methoxychlor exposure, and to a lesser extent by male exposure. Overall, these results suggested that sensitivity to methoxychlor is most dramatic during the reproductive and metamorphic phases of the life cycle and least sensitive during early embryo-larval development.

Animals↗

PubMed2004

Evaluation of the developmental and reproductive toxicity of methoxychlor using an anuran (Xenopus tropicalis) chronic exposure model.

The chronic toxicity of methoxychlor to the South African clawed frog, Xenopus (Silurana) tropicalis, was evaluated using a life cycle approach. The chronic exposure period ranged from mid-cell blastula stage [NF (Nieuwkoop and Faber, 1994) stage 8] to 90 days of exposure, during which time the organisms generally completed metamorphosis and emerged as juvenile frogs. Methoxychlor concentrations ranged from 1 to 100 micrograms/l. Methoxychlor concentrations >10 micrograms/l caused delayed development. Organisms exposed to 10 micrograms/l methoxychlor for 30 days showed enlarged thyroid glands with follicular hyperplasia. No increase in mortality or external malformation was observed at any of the test concentrations during early embryo-larval development (NF stage 8 to NF stage 46; ca. 2 days exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted after 90 days of exposure, however. Skewing of the sex ratio toward the female gender decreased ovary weight and number of oocytes, and increased oocyte immaturity and necrosis were noted at methoxychlor concentrations of 100 micrograms/l. Reductions in testis weight and sperm cell count were also detected at 100 micrograms/l methoxychlor. Results from these studies suggested that methoxychlor was capable of altering the rate of larval development, but did not adversely affect early embryo-larval development (2 days of exposure) as manifested in external malformations. Internal malformations, increases in the ratio of phenotypic females, were induced by chronic methoxychlor exposure. In addition, reproductive endpoints, most notably in the female specimens, were adversely affected by methoxychlor exposure. These studies add to the standardization and validation of a useful amphibian test methods capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.

Animals↗

PubMed2004

Aortic disasters.

TAD and AAA are two of the highest risk disease entities in emergency medicine. Emergency physicians should be vigilant in their approach to patients who have symptoms compatible with acute aortic disease. In chest and abdominal pain presentations, the chart must look like there was a search for the TAD and AAA. By having a sound knowledge of atypical cases;, having an appreciation for how subtle TAD and AAA can be; and recording and documenting a thorough history, physical examination, and risk factor profile, the emergency physician may reduce substantially the risk of missing a diagnosis and subsequently being sued. Emergency physicians cannot diagnose every case of acute aortic disease; what they can do is practice with a sound understanding of risk management principles and consider these diagnoses in all patients with chest, back, or abdominal pain.Ultimately, this strategy would provide protection for the patient and the physician.

Acute Disease↗

PubMed2003

The Brugada syndrome.

Brugada syndrome describes the syndrome of sudden cardiac death in the setting of the following electrocardiographic findings: right bundle branch block pattern with ST-segment elevation in the right precordial leads. The right bundle branch block may be incomplete while the ST segment elevation is minimal. The electrocardiographic findings are not constant. Patients suspected of having Brugada syndrome should be promptly referred for electrophysiological testing and treatment. Rapid referral and placement of an implantable cardioverter defibrillator (ICD) is associated with an excellent prognosis, whereas failure to diagnose this condition is associated with a high risk for sudden death. Therefore, it is imperative that all emergency physicians be familiar with the typical ECG manifestations of Brugada syndrome. Three illustrative cases are presented with a review of the syndrome.

Adult↗

PubMed2003

Evaluation of the developmental toxicities of ethanol, acetaldehyde, and thioacetamide using FETAX.

Potential mechanisms of the developmental toxicities of ethanol, acetaldehyde, and thioacetamide were evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X. laevis embryos were exposed to ethanol and thioacetamide in two separate definitive concentration-response tests with and without differentially induced exogenous metabolic activation systems (MAS) or selectively inhibited MAS. Two concentration-response tests were also performed with ethanol metabolites, acetaldehyde and acetic acid. The MAS was treated with 3,4-amino-1,2,4-triazole to modulate CYP2E1 activity, and heat to inactivate flavin containing monooxygenases (FMO) activity. Results from these studies suggested that thioacetamide may be bioactivated by both CYP2E1 and the FMO systems. Ethanol also appeared to be bioactivated by CYP2E1. Acetaldehyde was markedly more potent as a developmental toxicant than ethanol or acetic acid. Binary joint mixture studies conducted with ethanol and acetaldehyde indicated that the parent compound and metabolite acetaldehyde acted in a response additive manner. These results warrant the continued use of FETAX as a means of evaluating mechanisms of developmental toxicity in vitro.

Acetaldehyde↗

PubMed2003

Evaluation of Xenopus tropicalis as an alternative test organism for frog embryo teratogenesis assay--Xenopus (FETAX).

As a formal recommendation from an Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) workshop review of the Frog Embryo Teratogenesis Assay--Xenopus (FETAX) developmental toxicity model, the use of Xenopus tropicalis as an alternative test species for this model was evaluated. Three test substances with varying developmental toxicity potentials were evaluated using FETAX modified to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with isoniazid, methotrexate, and 6-aminonicotinamide. Historical FETAX results with X. laevis were compared to the results from FETAX assays with X. tropicalis. Test with X. tropicalis indicated that each of the compounds possessed teratogenic potential with varying degrees of potency: 6-aminonicotinamide > methotrexate > isoniazid. Based on overt teratogenicity, but not embryo-lethality, results from these studies indicated that these two species responded similarly to the test compounds. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis should be further evaluated as an alternative test organism for the FETAX model.

6-Aminonicotinamide↗

PubMed2002

Effect of endocrine disrupting chemicals on germinal vesicle breakdown in Xenopus in vitro.

Currently, no standardized and well-validated alternative models exist for screening for progesterone-responsive endocrine disrupting chemicals (EDCs). Because of this, a rapid assay for evaluating progestin/antiprogestin activity using Xenopus oocyte germinal vesicle breakdown (GVBD) as a model was evaluated. Five compounds, including progesterone (P), ethinyl estradiol (EE), ethylene glycol monomethyl ether (EGME), cadmium (Cd), and boric acid (B) were used to validate the model on a preliminary basis. Each test material was tested for progestin/anti-progestin activity. The binding affinity of each test material to the oocyte plasma membrane receptor (OPMR) relative to progesterone was then determined. Results from the present studies suggested that both EE and EGME were capable of inhibiting GVBD in a concentration-dependent manner. Cd had a subtle inhibitory effect at high concentrations. B had no effect on GVBD even at concentrations of 100 mg B/L, and thus appears to have no EDC activity in this model. The binding capacity of the test substances to the OMPR relative to progesterone was low. Thus, the relative inhibitory potential of the test materials study was EE > EGME >> Cd > B. However, the relative binding affinity of the toxicants to the OMPR can be expressed as P >> EGME > EE > Cd > B. Although EE was more effective in inhibiting GVBD, EGME appeared to bind more tightly to the OMPR.

Animals↗

PubMed2002

Impact of boron deficiency on Xenopus laevis: a summary of biological effects and potential biochemical roles.

The toxicity of boron has been understood for many years. However, limited data currently exist concerning the nutritional essentiality of B in chordates. Results from an ongoing research program evaluating the nutritional essentiality of B in the South African clawed frog, Xenopus laevis, found that X. laevis fed a low-B diet in a low-B culture media produced a substantially higher number of necrotic eggs and fertilized embryos than frogs fed a boron-sufficient diet. Markedly decreased embryo cell counts at mid-blastula transition and an increased frequency of abnormal gastrulation were also noted in embryos from adult frogs fed the B-deficient diet. By 96 h of development, none of the larvae collected from the B-deficient adults and maintained in low-boron culture media developed normally. Reproductive effects associated with B deficiency in female Xenopus included ovary atrophy, oocyte necrosis, and incomplete oocyte maturation. In males, a decrease in testis weight and sperm count was noted. These studies suggest that these adverse effects resulting from B deficiency could be found during gametogenesis, gamete maturation, embryonic development, and larval maturation. The studies also confirmed that B deficiency was capable of interrupting the X. laevis life cycle. Additional studies evaluating the role of B in the thyroid axis and the oocyte plasma membrane progesterone receptor provide the first line of direct evidence for a biochemical role of boron in X. laevis. Combined together, this research program provides firm evidence that B is nutritionally essential in X. laevis.

Animals↗

PubMedDate not supplied

Comparative sensitivity of Xenopus tropicalis and Xenopus laevis as test species for the FETAX model.

The use of Xenopus tropicalis as an alternative test species for the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) model was evaluated. Five test substances with varying developmental toxicity potential were evaluated using the traditional FETAX (X. laevis) and a modified assay to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with ethanol, semicarbazide, copper, 6-aminonicotinamide (6-AN) and atrazine. In order to evaluate the impact of culture temperature on species sensitivity, tests with X. tropicalis were performed concurrently at 27 degrees C (optimum temperature) and 23 degrees C (traditional FETAX temperature). Tests with X. laevis were performed only at 23 degrees C (optimal for X. laevis). Regardless of culture temperature, tests with X. laevis and X. tropicalis indicated that each of the compounds possessed teratogenic potential: semicarbazide>6-AN>atrazine approximately copper>ethanol. Results from these studies indicated that these two species responded similarly to the test compounds. Xenopus tropicalis was somewhat less sensitive to 6-AN, semicarbizide and atrazine when tested at 27 degrees C than at 23 degrees C. Ethanol, copper and atrazine were reasonably equipotent in X. tropicalis and X. laevis in terms of teratogenic response (EC50 for malformation), whereas 6-AN and semicarbizide were less potent in X. tropicalis than in X. laevis. No substantial differences (order of magnitude) in potency were observed between X. laevis and X. tropicalis with any of the test materials evaluated. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis could be used effectively as a test organism for the FETAX model.

Abnormalities, Drug-Induced↗