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Biomedical subjects

R B Paulson

Publications and source records attributed to R B Paulson.

At least 19 recordsLinked to original sources
PubMed1995

A scanning electron-microscopic study of tongue development in the frog Rana pipiens.

Feeding behaviour changes drastically during metamorphosis as larval suction feeders become adult lingual feeders. In order to understand this transition, the general morphological development of the floor of the buccal cavity in embryonic and larval Rana pipiens was studied, up to the completion of metamorphosis, by scanning electron microscopy. Rana pipiens specimens were collected, anaesthetized with tricaine methanesulphonate, staged by the methods of Shumway and Taylor and Kollros, and fixed in 0.1 M phosphate-buffered 2.5% glutaraldehyde. The oropharyngeal floors were dissected and routinely prepared for scanning. The late embryonic period (Shumway stages 21-25) is marked by the appearance on the oropharyngeal floor of two midline premetamorphic lingual papillae (PMLP), located on the second branchial arch just caudal to the hyomandibular groove. The larval tongue anlage, which incorporates PMLP along its anterior border, does not appear until stage V of the premetamorphic developmental span (Taylor-Kollros stages I-XI). Prometamorphosis (stages XII-XIX) is marked by the incorporation of the larval tongue into the adult tongue, the disappearance of the PMLP, and the appearance of the true tongue papillae. The metamorphic span (stages XX-XXIV) marks further rapid growth and differentiation of the adult tongue.

Animals↗
PubMed1994

Behavioral effects of smokeless tobacco on the neonate and young Sprague Dawley rat.

Three dosages of Smokeless Tobacco (ST) extract were given to pregnant Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The three dosages contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), 4.0 mg/kg nicotine (STD-2), and 6.0 mg/kg nicotine (STD-3). Dams were intubated three times per day at 8 a.m., 11 a.m., and 2 p.m., providing total daily ST dosages of 4 mg/kg, 12 mg/kg, and 18 mg/kg, respectively. Controls received equivalent volumes of water by gavage. Dams were allowed to deliver, and all biological mothers raised their own pups. On postnatal day 1 (PND 1), litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included surface righting, negative geotaxis, swimming development, open field activity, and active avoidance in shuttle box. Our results show that the two higher doses resulted in reduced maternal weight gain. During the pre-weaning period, significant pup weight reductions were noted in the STD-2 pups until PND6, and in the STD-3 group until PND15. In the STD-1 group no statistically significant weight reduction was noted on PNDs 1 and 3, but starting with PND6, pup weights surpassed control group weights. This weight difference persisted throughout the post-weaning period also (P < .05 on PND30 and PND42). The STD-3 pup weights continued to be consistently and significantly (P < .05) reduced throughout the post-weaning period (except on PND24); likewise, the STD-2 pups continued to have lower weights, but at a significant level (P < .05) on PND30 only. The incidence of deaths was increased in a dose-related manner. No significant differences were noted for pinna detachment and incisor eruption; however ST-treatment was significant in affecting earlier eye opening and vaginal patency. N significant ST treatment effects were seen on negative geotaxis, but for surface righting a decreased success rate was noted for the ST-treated groups. Significant differences were noted in swimming development, with the STD-2 pups performing best. Open field activity, as expected, increased from the pre-weaning to post-weaning periods. During the pre-weaning period the STD-3 pups were more active, and during post-weaning the STD-1 pups were more active, but no differences were noted in vertical activity or in the number of stereotypical movements. No treatment-related differences were noted in the active avoidance shuttle box.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Teratogenic effects on the neuroepithelium of the CD-1 mouse embryo exposed in utero to sodium valproate.

A causal association has now been recognized between the use of the anticonvulsant drug sodium valproate during pregnancy and the increased incidence of spina bifida in the human population. The objective of this study was to investigate the teratogenic effects of sodium valproate on the cephalic 1) neuroepithelium, 2) extracellular matrix, and 3) embryonic protein content in the CD-1 mouse embryo. Nulliparous female CD-1 mice were dosed intraperitoneally on day 8 of gestation with 340 mg/kg of sodium valproate. On day 10 of gestation, females were killed by cervical dislocation, and all live embryos were assigned to one of the following groups and processed accordingly for: 1) head measurements, 2) scanning electron microscopy, 3) total protein determination, 4) two-dimensional polyacrylamide gel electrophoresis, 5) immunohistochemistry, and 6) light microscopy. Exposure to sodium valproate at the selected dosage resulted in a 30% incidence of neural tube defects in the cranial region of these embryos. Treated embryos showed a significant reduction in head size, indicating a drug-induced microcephaly. No major differences were seen in the total embryonic protein patterns between control and treated embryos. Immunoreactivity to laminin and fibronectin showed a similar distribution in control and treated embryos except in the vasculature pattern of the hindbrain neuroepithelium. The neuroepithelium of the treated embryos showed marked disorganization when it was examined histologically, particularly in the forebrain region. Cells were disoriented, and there was a noticeable loss of intercellular adhesion in the juxtaluminal region. Increased cellular blebbing was apparent at the ependymal surface, and large protrusions of cells were seen invading the neural tube lumen. The lumen was distorted in shape and frequently contained blood cells. Irregularities and gaps were observed in the underlying basal lamina. These results suggest that treatment with sodium valproate during a critical time in neurogenesis in the CD-1 mouse embryo alters the normal architecture of the neuroepithelium, with a loss of integrity at both the basal and apical surfaces. The alterations seen in the neuroepithelium at any of these sites in this animal model could help explain the increased incidence of spina bifida seen in children of epileptic mothers receiving sodium valproate.

Abnormalities, Drug-Induced↗
PubMed1989

Effects of sodium valproate and oxygen on the craniofacial skeletal pattern in the CD-1 mouse embryo.

Growth retardation is a consistent finding in animal studies on the effect of sodium valproate (NaVP) in the embryo. Apart from fetal weight, the state of ossification in the embryo may be regarded as an indication of growth. The present study was to determine what effect sodium valproate at human therapeutic drug plasma levels had on the craniofacial skeletal pattern in the CD-1 mouse embryo relative to oxygen conditions, drug treatment or the interaction of the two. Two NaVP-filled Alzet osmotic minipumps were implanted subcutaneously on day 5 of gestation for continuous delivery of a total daily dosage of 850 mg/kg for 7 days. During this same time period the dams were also exposed to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments. Dams were removed from the oxygen chambers on day 12 and killed on day 18 of gestation. The fetuses were then processed for skeletal evaluation of the craniofacial region. Ossification centers were present in all but six of the skeletal elements studied. The primary ossification delay was in the tympanic bony labyrinth. In addition, there was a decrease in maxillary and mandibular length and cranial base measurements. The greatest toxic effect on the fetus for all skeletal components studied was in the NaVP/hypoxia treated group. This finding suggests that fetal skeletal maturation may be affected by a combination of intrauterine as well as external factors.

Animals↗
PubMed1988

Effects of sodium valproate and oxygen on the CD-1 mouse fetus.

This study reports the effects of valproic acid (VA) on the CD-1 mouse fetus when the drug is administered continuously via osmotic minipumps at human therapeutic drug plasma levels. Two VA-filled Alzet osmotic minipumps were implanted subcutaneously on gestation day 5 for continuous exposure of a total daily dosage of 850 mg/kg on gestation days 5-12. Dams were then exposed continuously to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments during gestation days 5-12, in order to determine if hyperoxic maternal conditions offered a protective environment for the fetus, and conversely, if hypoxia exacerbated teratogenicity. Dams were sacrificed on gestation day 18, and litter and fetal data were collected. It was determined in separate groups under normoxic conditions that the osmotic minipump system maintained VA plasma levels corresponding to human therapeutic levels. Sodium valproate was found to induce developmental toxicity in the CD-1 mouse fetus at human therapeutic drug plasma levels. Fetal weights were reduced, and the number of resorptions, deaths, and hematomas was increased. While hypoxia exacerbated the toxic effect on the fetus, hyperoxia failed to ameliorate the outcome.

Animals↗
PubMed1986

Scanning electron microscopy of developing human deciduous incisor teeth.

The mineralized parts of the teeth of 17 human fetal dentitions, aged 15-38 weeks, were measured mesio-distally and occluso-cervically. The growth pattern of the incisors, with particular emphasis on the changes at the developing incisal edge was studied. Contralateral teeth in the same arch developed at approximately the same rate and with mirror-image morphology. Mineralization started in the upper and lower central incisors, followed by the corresponding lateral incisors. It then progressed at approximately the same rate for both incisors. At first, mesio-distal enamel growth was more significant, but was surpassed by occluso-cervical development later. Five development stages were identified as the incisors developed from a central lobe to the mature form. The main component of growth for the mesial lobe was in the incisal direction, and for the distal lobe in a distal direction, resulting in the characteristic approximal asymmetry of these teeth.

Humans↗
PubMed1985

Teratogenic effects of valproate in the CD-1 mouse fetus.

Valproate sodium has been implicated in the production of spina bifida in humans; this article reports an animal model. Teratogenicity of valproate sodium was studied by oral administration of single doses of 225, 340, and 560 mg/kg to pregnant CD-1 mice on days 7 through 12 of gestation. All fetuses were examined on day 17. Treated fetuses demonstrated external malformations and a decrease in weight. The incidence of malformations was greater at the higher dosage levels of 340 mg/kg and 560 mg/kg, with a predominance of exencephaly, open eyelids, and gross skeletal defects. There was a significant increase in the resorption rate of the fetuses in the treated groups. There was also a significant increase in the malformations observed per litter and per live fetus population when compared with controls.

Abnormalities, Drug-Induced↗
PubMed1985

Scanning electron microscope study of tongue development in the CD-1 mouse fetus.

The objective of this study was to examine three dimensionally the embryonic and fetal stages of tongue development with scanning electron microscopy. Time-bred CD-1 mice were sacrificed at quarter-day intervals on days 10-13, and at half-day intervals on days 13.5-16.5 of gestation. Fetal tongues were dissected and fixed in s-collidine buffered 4% glutaraldehyde at pH7.4, and subsequently processed for SEM viewing. Tongue development was initiated on the 11th day by the appearance of the tuberculum impar and the two lateral lingual swellings on arch I. This was followed by the elevation of the hypobranchial eminence, which unites arches III and IV in the ventral midline, and overgrows arch II anteriorly. During the 12th day, remodeling occurred in areas of arches II and III, forming the root of the tongue. A cone-shaped midline swelling, the epiglottis, appeared in the ventral midline of arches III and IV. By the 13th day, the general proportions of the tongue, occupied by the body, root, and epiglottis, were established. The single circumvallate papilla and fungiform papillae were initiated during the early part of the 13th day, followed on the 15th day by differentiation of filiform and foliate papillae and raised nodules of lingual tonsilar tissue. The SEM study documented the temporal and morphological sequence of events during mouse tongue development. The tuberculum impar persisted to the late fetal stages and may therefore contribute largely to the dorsum of the tongue anterior to the circumvallate papilla.

Animals↗
PubMed1984

Teratogenic effects of dosage levels and time of administration of carbamazepine, sodium valproate, and diphenylhydantoin on craniofacial development in the CD-1 mouse fetus.

The objective of this investigation was to study the teratogenic effects of dosage levels and time of administration of three anticonvulsant drugs (carbamazepine [CMZ], sodium valproate [NaV], and diphenylhydantoin [DPH]) on craniofacial development in the CD-1 mouse fetus. Pregnant females were intubated on each of days 8-10, 11-13, 14-16, and 8-16 of gestation with the following dose levels for each drug: 375, 563, 938 mg/kg CMZ; 225, 338, 563 mg/kg NaV; 50, 75, 125 mg/kg DPH. Appropriate control groups were maintained for each drug. On gestation day 17, pregnant females were killed and implantation sites were recorded as live, dead, or resorbed. All live fetuses were examined for craniofacial defects. Results of examination of 1,398 fetuses indicated that CMZ, NaV, and DPH were teratogenic and embryotoxic at all dose levels. This study indicated that the observed decrease in mean fetal weight was drug-, dose-, and time-dependent. There was a drug-, dose-, and time-dependent increase observed in the number of dead fetuses, whereas the number of resorbed fetuses was observed to be only time-dependent. The observed frequencies of hydrocephalies, secondary palatal clefts, and submucous palatal clefts were significant for all three factors (drug, dose, and time) whereas the observed frequencies of hematomas and exencephalies were significant only for drug and time. Cleft lips were observed only in the highest dose level of DPH. Uterine horn distribution of defects indicated that fetuses located at the proximal end of the horns were less subject to major defects than those fetuses located at the distal end of the uterine horns. Fetuses with craniofacial hematomas were found in the proximal one-third of the uterine horn, resorbed fetuses, and fetuses with submucous palatal clefts in the middle one-third of the uterine horns and dead fetuses and fetuses with exencephalies, cleft lips, and secondary palatal clefts were localized in the distal one-third of the uterine horns. In comparing the effect of drug, dosage, and time on the development of craniofacial malformations in the CD-1 mouse fetus, CMZ was the least teratogenic and embryotoxic of the three anticonvulsant drugs employed in this study.

Abnormalities, Drug-Induced↗
PubMed1981

Teratogenic effects of anticonvulsants.

The incidence of malformations in fetal mice exposed to phenytoin depends on drug dosage and the strain of mice. Animal research also suggests that most anticonvulsants are teratogenic in experimental animals when large doses are used, but the effect of valproate sodium on the fetus is poorly known. Cleft lip and palatal defects have been most extensively studied, but defects have also been noted in eyes, heart, and limb buds. Data from humans are less clearer than the animal data, but human maternal exposure to anticonvulsants may increase infant clefting by threefold to tenfold. If a woman at risk for childbearing is given anticonvulsants for the first time, carbamazepine may be given first. Before pregnancy, the true need for anticonvulsants should be reassessed, but abrupt discontinuation of anticonvulsants during pregnancy is not now recommended.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Behavioral effects of prenatally administered smokeless tobacco on rat offspring.

Two dosages of Smokeless Tobacco (ST) extract were given to gravid Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The low dosage contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), and the high dosage contained ST extract equivalent to 4.0 mg/kg nicotine (STD-2). Dams were dosed three times daily at 8 a.m., 11 a.m., and 2 p.m., thus providing total daily nicotine equivalent dosages of 4 mg/kg/day and 12 mg/kg/day. Controls received equivalent amounts of distilled water by gavage. Dams were allowed to deliver and all experimental pups were fostered to control mothers. On postnatal day 1 (PND 1) litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included: surface righting, negative geotaxis, swimming development, open-field activity, active avoidance in shuttle box, and Cincinnati swimming maze. Our results show that the STD-2 dose resulted in reduced maternal weight gain. Offspring weights were reduced in a dose-related manner, with the most consistent weight deficits seen in the STD-2 group until PND29. Consistent STD-1 weight deficits were seen up to PND 8. The incidence of deaths was increased in the STD-2 dosage group. No significant treatment-related differences were observed in development of physical landmarks. Male STD-2 pups righted faster than controls, and significant differences were noted in swimming development with the STD-1 group of pups performing less effectively than controls. Activity levels, assessed during both pre- and post-weaning periods were not affected. No treatment-related differences were seen in the active avoidance shuttle box or Cincinnati swimming maze tests, which assessed learning. Female brain weights were reduced in the STD-1 treatment group.

Animals↗
PubMedDate not supplied

Parkinson's disease: a review and recommendations for dental management.

Parkinson's disease is one of a group of extrapyramidal diseases characterized by rigidity and tremor. The disease affects about 1 million persons in this country, and is most common in persons older than 55. Parkinson's is disabling and usually progresses from mild to severe, often in less than a decade, and may preclude an individual from accomplishing many activities of daily living, even with current drug therapy. In addition to problems caused by age, dental complications arise from the inability of the individual with Parkinson's to accomplish routine oral hygiene, from changes in salivary flow and due to dysfunction in swallowing. Dental management of individuals with Parkinson's is a multifaceted challenge involving areas of preventive, restorative, and prosthetic dentistry. Support is also required for the psychosocial and behavioral aspects of this common progressive disorder.

Dental Care for Persons with Disabilities↗
PubMedDate not supplied

Alcohol and smokeless tobacco effects on the CD-1 mouse fetus.

Tobacco products and alcohol are commonly used as nonmedicinal drugs by pregnant women, and both are known to cause various effects on the fetus and the newborn. The objective of this study was to examine the fetal effects of both drugs when administered individually and simultaneously to pregnant CD-1 mice at moderate dosages. Specifically, we wanted to determine whether or not the effect on the fetus of these two biologically active substances was additive, ameliorative, or synergistic. A total of 65 CD-1 dams were divided among four groups receiving either ST equivalent to 8 mg/kg nicotine, ethanol (ETOH) 1.8 g/kg, a combination of ST+ETOH in the same dosages, or D-glucose (controls and ST alone) to supply calories equivalent to the dose of ethanol. Mice were dosed three times per day on gestational days 6-15. On gestational day 17 all dams were killed, fetal and placental weights recorded, and the number of resorbed, dead, and malformed fetuses noted. The mean maternal plasma drug levels were: nicotine-321 ng/ml and ethanol-0.105 g%. No significant differences were observed in maternal weight gain, litter size, or in the incidence of resorptions, deaths and/or malformations. Fetal weights were reduced in all three treatment groups (P less than 0.05), with the greatest reduction (13% decrease) recorded in the ST group, followed by a 9% decrease in the ETOH group, and a 7% decrease in the ST+ETOH group. Placentas of the ST group weighed significantly less (P less than 0.05) than controls. Ossification of the fetal skeleton, observed in ten sites, was affected to the greatest extent in the ST group, followed by the ETOH and ST+ETOH groups. Craniofacial measurements were significantly affected (P less than 0.05) in all three treatment groups, compared to controls. We conclude that under these experimental conditions, in terms of fetal growth and ossification, ST had the greatest effect, followed by ETOH and ST+ETOH. The interaction of ST+ETOH was neither additive, synergistic, nor ameliorative.

Analysis of Variance↗
PubMedDate not supplied

Pre- and post-conceptional tobacco effects on the CD-1 mouse fetus.

The objective of this study was to examine the effect of subchronic administration of an aqueous extract of smokeless tobacco (ST) on the development of the CD-1 mouse fetus. Mice were administered ST for approximately 5 weeks: for 2 weeks prior to breeding, during breeding, and during gestational days 0 to 17. Thus the initial peak nicotine levels occurred prior to breeding and not during the critical periods of gestation. Two ST dosages were administered by gastric intubation three times daily: ST/D-1, equivalent to a dose of 12 mg nicotine/kg of body weight, and ST/D-2, equivalent to 20 mg nicotine/kg body weight. Maternal plasma nicotine levels were determined 30 min after the second intubation during the pretreatment and gestational phases of treatment. At these ST dosages, the weight gain of ST-treated dams was not significantly affected in comparison to treated controls. The mean maternal plasma nicotine level for the low-dosage group was 363 ng/ml, and 481 ng/ml for the high-dosage group, with maternal lethality observed at 9.6% and 28.2%, respectively. No significant differences were seen between control and ST/D-1 maternal and/or fetal values, except for placental weights which were heaviest in the ST group (P less than 0.05). Several differences were noted between the ST/D-2 group and controls: fetal weights were reduced by 5.4% (P less than 0.05); decreased ossification was seen in femur measurements and in nine of ten characteristics measured (P less than 0.05); the frequency of resorptions (7.6%) was almost doubled (controls 4.2%); and the frequency of deaths and malformations was not affected. Under these experimental conditions, the low dose produced a negligible effect on the CD-1 mouse fetus and the dam. The high dose demonstrated growth retardation (P less than 0.05), increased embryotoxicity, and a significant decrease in ossification (P less than 0.05).

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Double-rooted maxillary primary canines.

This paper includes morphological descriptions of bifurcated maxillary primary canines. Three major primary canine root types are recognized: A single root without trace of a groove, a root with a faint to distinct labial groove, a root with a broad and deep labial groove in the apical portion of the root.

Child↗