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Biomedical subjects

L M Newman

Publications and source records attributed to L M Newman.

51 records · Page 3Linked to original sources
PubMed1983

Oxygen consumption and survival prediction in neonatal rats exposed to prenatal hypervitaminosis A.

Fetal exposure to excess vitamin A results in a highly variable degree of lung pathology and high neonatal mortality in the Long-Evans rat. The present study evaluated O2 consumption in newborn of vitamin A-treated, vehicle-treated, and untreated pregnancies on five consecutive postnatal days beginning with the day of delivery (D0). Pregnant female rats were treated by gavage with 160,000 USP units of retinyl acetate dissolved in 0.5 ml corn oil on days 15 through 19 of gestation. Vehicle and undisturbed controls were run concurrently. All animals delivered spontaneously, and the pups were tattooed and individually tested in a closed system consisting of three chambers submerged within a thermostatically controlled water bath at 33 degrees C. Vitamin A-exposed pups, as a group, have significantly lower QO2 (ml O2 consumed/min/kg body weight) values than controls through postnatal day 2 (p less than 0.05). By days 3 and 4 of age, the mean QO2 values of surviving vitamin A-treated pups were similar to those of controls. A QO2 of 30 or greater on day 0 appears to be critical for early neonatal survival of vitamin A-exposed pups, as 87% of the pups with initial QO2 less than 30 died prior to day 4. Oxygen consumption rates in teratogen-exposed pups exhibiting low QO2 on day 0 rarely reached normal levels. In contrast, the occasional control pup with such low initial levels were well within normal limits (means +/- 1 SD) by the following day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Intralitter variation of neonatal rat lung morphology following prenatal maternal hypervitaminosis A.

Prenatal exposure to excess vitamin A (160,000 USP units/day) from days 15 through 19 of gestation results in altered lung morphology, characterized by thickened septal walls and/or large areas of atelectasis and an associated high neonatal mortality. Marked variability in both morphological and physiological expression from this prenatal insult is commonly seen between litters and littermates, making analyses difficult. The present study documents morphological intralitter variation observed in vitamin A-exposed 2-day-old rats as compared to controls. Representative midhilar coronal histological sections of each lung were examined by two methods and the results compared. The first method, although less sensitive, demonstrated that five out of eight experimental rat lungs had a significantly greater percentage of tissue to airway space as compared with undisturbed controls (greater than 43%). The second method, using several morphological criteria and a grid system to score parenchyma into classifications based on the degree of morphological variation and projected functional capability, clearly found significantly increased percentages of poor or nonfunctional lung tissue (P greater than 0.01) in seven out of eight pups exposed to excess vitamin A. This method of ranking the severity of adverse effects on tissue morphology allowed identification of drug-affected newborn and provided a means to quantify the alterations. Such a means for identifying affected individuals from littermates is essential to research methodologies for detecting substances which, when administered during fetal life, produce decrements of postnatal function but no gross structural abnormalities.

Animals↗
PubMed1981

Introduction of late gestational teratogenesis in rat lung by hypervitaminosis A.

Long-Evans black-hooded rats treated via stomach tube with 160,000 USP units of retinyl acetate (vitamin A) in 0.5 ml Mazola corn oil on gestational days 15--19 deliver normal-sized litters with significantly decreased viability. Vitamin A is known to effect the differentiation and to stimulate the growth of epithelial cells. Additionally, lung epithelia undergo marked morphologic and physiologic changes late in gestation. Thus the effects of hypervitaminosis A on developing lung constitute an excellent system for the study of teratogenesis late in gestation. Non-hilar, right lower-lobe sections of lungs from the vehicle control and experimental groups, compared via quantitative light microscopy, revealed no significant difference in gross overall histologic appearance on any given day, either in the total number of airways present in the volume of lung sectioned or in the percent area of any individual airway occupied by cells or by lumen. The only significant difference was in the number of cells per square micrometer in that region of an airway occupied by cells. Additionally, there was a significant difference between the control and experimental mitotic indices on gestational days 18 and 19. Thus in the experimental group the number of cells lining the developing airways increases, while the absolute thickness of this cellular layer remains constant. Transmission electron microscopy (TEM) fails to reveal any morphologic differences between control and treated type II pneumatocytes. The increased number of respiratory cells in what otherwise appears to be normal lung may create a diffusion-perfusion imbalance or other difficulties contributing to the heightened neonatal mortality resulting from teratogen exposure late in gestation.

Animals↗
PubMed1981

Fetal ear malformations induced by maternal ingestion of thalidomide in the bonnet monkey (Macaca radiata).

Gross malformations of the external, middle, and internal ear were seen in fetal monkeys following maternal ingestion of thalidomide. Twenty-five pregnant bonnet monkeys (Macaca radiata) were each given a single oral dose of 10 mg/kg of thalidomide on day 24, 25, 26, 27, 28, or 29, or 30 mg/kg on day 25 or 28 of gestation. (Day of mating is assumed to be day zero of pregnancy). The skeletons, processed and stained with Alizarin Red S, were examined for changes in configuration and/or ossification of the ossicles and temporal bones. Bilateral temporal bones of one case, treated on day 24, were sectioned at 10 microns and examined histologically. Twelve fetuses collected at 70 +/- 3 days of gestation showed no gross ear defects, while 10 out of 13 fetuses collected at 100 +/- 3 days of gestation had structural anomalies similar to those observed in humans. All malformations were severe in fetuses treated on day 24 of gestation and lessened in degree of severity with treatments on days 25-28. Fetuses treated on day 29 were normal. External ear anomalies included microtia with meatal atresia or stenosis, and varying degrees of auricular hypoplasia. Defects of the middle ear were predominantly hypoplasia of malleus, incus, and tympanic ring. Fused ossicles and cochlear and vestibular window abnormalities were only seen in animals treated on day 24. The internal ear exhibited petrosal hypoplasia and delayed ossification of the lateral aspect of the lateral and posterior semicircular canals. Cochlear, vestibular, semicircular, and transcapsular canal defects were confirmed histologically in one case.

Abnormalities, Drug-Induced↗
PubMed1980

The tear-drop capsulectomy and capsulorrhaphy: a new approach in aiding the soft tissue repair of hallux abducto valgus.

Capsular correction is an important part of the repair of hallux abducto valgus. In this paper, the authors discuss the tear-drop method of capsular repair--a method that can be used in all hallux valgus corrections, either alone or in conjunction with the dorsolinear capsulotomy and repair. They believe the tear-drop method has many advantages, among which is the fact that severe splinting and/or casting is not needed and the patient can walk in a surgical shoe almost immediately after surgery. Excellent results were obtained in a high percentage of their 288 cases.

Connective Tissue↗
PubMed1978

Reproduction of the greater bushbaby (Galago crassicaudatus panganiensis) under laboratory conditions.

A breeding colony of Galago crassicaudatus panganiensis was maintained under laboratory conditions for four years, August 1971 to July 1975. The estrous cycle and the gestation period averaged 39 and 132 days in length, respectively. Twinning occurred in 14.5% of the pregnancies. No postpartum estrus was observed, although 1.2 conceptions per female per year were recorded. Breeding occurred throughout the year. Puberty occurred between ten and 18 months of age, the first conception occurred between 15 and 18 months of age, and reproductive capability decreased rapidly between ten and 12 years of age.

Animals↗
PubMed1973

Metabolism of Richettsia tsutsugamushi and Rickettsia rickettsi in irradiated host cells.

The metabolism of Rickettsia tsutsugamushi (Gilliam strain) multiplying in irradiated L cells was investigated by methods involving the use of (14)C-labeled substrates and cycloheximide, an inhibitor of eukaryotic metabolism. Cycloheximide-resistant amino acid and adenine incorporations were appreciably higher in infected than in uninfected cultures during the period from 3 to 5 or 6 days postinoculation. The metabolism of R. rickettsi was similarly studied in primary duck embryo cells, which are more susceptible to infection with this rickettsia than are L cells. A difference in cycloheximide-resistant activity between infected and uninfected cultures was also noted, but was small. This finding is attributed to the more limited growth of R. rickettsi.

Amino Acids↗
PubMed1972

9 -Tetrahydrocannabinol and ethyl alcohol: evidence for cross-tolerance in the rat.

Rats trained in a one-way avoidance situlation were made tolerant to the depressant effects of Delta(9)-tetrahydrocannabinol. Ethyl alcohol (3.2 grams per kilogram, intraperitoneally) did not greatly affect rats that were tolerant to delta(9)tetrahydrocannabinol but depressed the behavior of nontolerant rats. Rats made tolerant to ethyl alcohol were less affected by Delta(9)-tetrahydrocannabinol.

Animals↗
PubMedDate not supplied

Assessment of the effectiveness of animal developmental toxicity testing for human safety.

Evaluations of studies for four well-known human developmental toxicants clearly suggest that a margin of exposure of 1/100th the NOAEL for the most sensitive animal species tested provides adequate safety for the human conceptus. The lowest reported human teratogenic exposures occurred at doses at least one log above the estimated "safe" or acceptable daily exposure based on the most sensitive animal species, that is, 1/100th animal NOAEL. (The MOE ranged from < 1 to 10.). The data and analyses are consistent with the conclusion that, regardless of the type of in utero effect produced in animals, the margin of safety of 100 is likely to protect the human conceptus in utero from developmental perturbation, and it is a scientifically reasonable and conservative default number.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Multiple chemical exposures: synergism vs. individual exposure levels.

Exposure to single chemicals is known to produce congenital malformations in both pregnant animals and humans exposed at sufficiently high intensity. However, real life involves multiple, simultaneous exposures. Using as a database the 43 multiple chemical exposure studies located by Nelson (Teratology 49:33-71; 1994) where synergism was reported, we explored the degree to which such concerns may be realistic from the viewpoint of the current standard developmental toxicity safety evaluation process. Focusing on the assessment of the lowest tested dose of a given agent participating in synergistic activity as compared to its threshold level for eliciting toxicity when administered alone, we found that while the availability of adequate data was limited, all cases, with the possible exception of one, demonstrated synergistic toxic expression only when at least one, and usually both, compounds were used at or above their individual threshold for toxicity. These findings suggest that in animals such phenomena of synergistic chemical interactions are likely to occur only when at least one and more likely both agents are administered at or above their individual threshold for toxicity. To the extent animal studies are predictive of human developmental hazards due to single chemical exposures, available data do not establish multiple chemical exposures as a major human developmental concern.

Animals↗