Biomedical subjects

Miroslav Peterka

Publications and source records attributed to Miroslav Peterka.

13 recordsLinked to original sources

PubMed2006

Study of feasibility of the treatment with procainamide hydrochloride and cisplatin in pregnant mice.

Cisplatin is one of the most widely utilized anticancer drugs; nevertheless its use is often hampered by the onset of serious side effects. In spite of its tight binding to DNA, great teratogenic effects do not characterize cisplatin, although its embryolethal and growth retardation activities are quite remarkable. On the basis of our previous observations, demonstrating the usefulness of procainamide hydrochloride for the protection against cisplatin toxic effects in adult mice and rats, we now analyze the feasibility of the combined treatment with cisplatin and the antiarrhythmic drug procainamide hydrochloride in pregnant mice and the possible protective action of procainamide against the embryotoxic activity of cisplatin. Our data, obtained in CD-1 dams after treatment with 8 or 12 mg/kg cisplatin ip, with or without 50 mg/kg procainamide hydrochloride iv, confirm the embryotoxic effects of cisplatin. We also demonstrate that procainamide may be administered with cisplatin without causing an increase in its embryotoxic effects, but slightly improving some embryotoxicity parameters in living embryos such as the fetal weight, the percentage of fetuses with skeletal anomalies, and the number of ossification centres. The mechanism of action of this partially protective activity seems to be linked in part to the lower cisplatin accumulation in fetal tissue, probably due to an interaction of drugs at the level of placenta, in part to the protection of procainamide against maternal toxicity of cisplatin. A relevant result of this research is the suggestion that procainamide hydrochloride might be administered in case of pregnancy to protect against the maternal toxic effects of cisplatin without an increased embryotoxic/teratogenic risk for the offspring.

Animals↗

PubMed2006

Phylogenetic memory of developing mammalian dentition.

Structures suppressed during evolution can be retraced due to atavisms and vestiges. Atavism is an exceptional emergence of an ancestral form in a living individual. In contrast, ancestral vestige regularly occurs in all members of an actual species. We surveyed data about the vestigial and atavistic teeth in mammals, updated them by recent findings in mouse and human embryos, and discussed their ontogenetic and evolutionary implications. In the mouse incisor and diastema regions, dental placodes are transiently distinct being morphologically similar to the early tooth primordia in reptiles. Two large vestigial buds emerge in front of the prospective first molar and presumably correspond to the premolars eliminated during mouse evolution. The incorporation of the posterior premolar vestige into the lower first molar illustrates the putative mechanism of evolutionary disappearance of the last premolar in the mice. In mutant mice, devious development of the ancestral tooth primordia might lead to their revivification and origin of atavistic supernumerary teeth. Similarity in the developmental schedule between three molars in mice and the respective third and fourth deciduous premolar and the first molar in humans raises a question about putative homology of these teeth. The complex patterning of the vestibular and dental epithelium in human embryos is reminiscent of the pattern of "Zahnreihen" in lower vertebrates. A hypothesis was presented about the developmental relationship between the structures at the external aspect of the dentition in mammals (oral vestibule, pre-lacteal teeth, paramolar cusps/teeth), the tooth glands in reptiles, and the earliest teeth in lower vertebrates.

Animals↗

PubMed2006

Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling.

Unlike humans, who have a continuous row of teeth, mice have only molars and incisors separated by a toothless region called a diastema. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. Here, we identify members of the Sprouty (Spry) family, which encode negative feedback regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase signaling, as genes that repress diastema tooth development. We show that different Sprouty genes are deployed in different tissue compartments--Spry2 in epithelium and Spry4 in mesenchyme--to prevent diastema tooth formation. We provide genetic evidence that they function to ensure that diastema tooth buds are refractory to signaling via FGF ligands that are present in the region and thus prevent these buds from engaging in the FGF-mediated bidirectional signaling between epithelium and mesenchyme that normally sustains tooth development.

Adaptor Proteins, Signal Transducing↗

PubMed2005

The developmental relationship between the deciduous dentition and the oral vestibule in human embryos.

In humans, there is no consensus about the developmental relationship between the deciduous dentition and the oral vestibule separating the teeth from the lips and cheeks. The classical concept assumes that two horseshoe-shaped epithelial structures exist: the dental lamina, giving rise to single tooth primordia, and the vestibular lamina running parallel and externally to it, giving rise to the oral vestibule. The aim of this study was to investigate the development of the dental and vestibular laminae in the upper jaw and to determine their developmental relationship in humans from embryonic week 6 to 9. Although a thickening of the vestibular epithelium was always present on serial histological sections, computer-aided three-dimensional reconstructions did not show any continuous vestibular lamina. Several discontinuous epithelial structures (bulges and ridges) occurred transiently at different stages of oral vestibule development. Along the mesiodistal axis, the dental and vestibular epithelia were regionalized in parallel: in the incisive, canine, and 1st and 2nd molar regions. The vestibular ridges fused with the dental lamina distally to the deciduous canine, 1st molar and 2nd molar. These interactions between the developing teeth and vestibular structures are reminiscent of the situation in some reptiles, where single teeth are paired one-to-one with single tooth glands.

Embryonic Development↗

PubMed2004

Origin and developmental fate of vestigial tooth primordia in the upper diastema of the field vole (Microtus agrestis, Rodentia).

OBJECTIVE: Odontogenesis in voles is a convenient model to test hypotheses on tooth development generated from investigations in the mouse. Similar to other rodents, the functional dentition of the vole includes a toothless diastema. At its mesial end, a vestigial tooth bud has been found in the upper jaw of vole embryos. The aim of this study was to analyse the developmental dynamics of vestigial tooth structures in the upper diastema of the field vole and to compare it with the situation in the mouse. DESIGN: The development of odontogenic structures in the upper diastema of the field vole was investigated using serial histological sections and three-dimensional (3D) computer-aided reconstruction. RESULTS: A transient continuous dental lamina in the upper diastema of the field vole extended mesially to the first molar primordium, but was not continuous with the dental lamina in the incisor region. At its mesial limit, a large vestigial tooth primordium was regularly present. A further distinct vestigial bud was located mesially to the first molar primordium. The segmentation of the dental lamina suggested a potential to give rise to further vestiges in the upper diastema of the vole. CONCLUSIONS: In the prospective diastema of the vole exists as in the mouse a continuous dental lamina. Beside the prominent vestigial tooth bud in the mesial diastema, a further large bud was transiently located in front of the molars. The incorporation of dental epithelium into the first upper molar (M(1)) primordium in the vole differs from that in the mouse.

Animals↗

PubMed2004

Three-dimensional analysis of maxillary dental casts using Fourier transform profilometry: precision and reliability of the measurement.

OBJECTIVE: Fourier transform profilometry was used for the three-dimensional measurement of maxillary dental casts to analyze the size and shape of the palate. The objective of this study was to test the accuracy of the measuring system and determine the precision and reliability of the measurement METHODS: Images of dental casts were analyzed using newly developed measuring software. Based on five landmarks located on the alveolar ridge, the measuring software constructed 10 transversal sections of the palate. In each section profile, the width, area, and 23 height variables were assessed. SUBJECTS: Maxillary dental stone casts of 25 healthy girls, 14.1 to 15.3 years of age, were studied. RESULTS: The technical error of measurement exceeded 5% of the size of the measurement only in variables with means less than approximately 3 mm. In fact, such small absolute dimensions were exhibited only by the palate height in anterior profile 2 and the palate height at the margins of other profiles. Reliability of the measurements was found to be very high for the width and area of the profiles. For height measurements, the coefficient of reliability was slightly lower at the profile margins than near the midline. Nevertheless, only three height variables showed a coefficient of reliability lower than 0.90. The coefficients of reliability of other height measurements of profiles 3 through 10 were only sporadically lower than 0.97. CONCLUSION: With regard to the accuracy of the measuring system as well as the precision and reliability of the measurement, this method proved to be a suitable tool for studying palatal morphology.

Adolescent↗

PubMed2004

Three-dimensional morphology of the palate in subjects with unilateral complete cleft lip and palate at the stage of permanent dentition.

OBJECTIVE: Three-dimensional analysis of palate size and shape in patients with complete unilateral cleft lip and palate (UCLP) at the stage of permanent dentition. SUBJECTS: Thirty randomly selected dental casts of boys approximately 15 years old with complete UCLP and 28 dental casts of normal boys of the same age. INTERVENTIONS: All patients underwent lip repair according to Tennison with primary periosteoplasty (mean age 8.5 months) and palate repair by pushback and pharyngeal flap surgery (mean age 4.9 years). MAIN OUTCOME MEASURES: Data on the palate height in 210 defined locations. RESULTS: The palate in patients with UCLP was narrower throughout its whole extent, more anteriorly than posteriorly. From the canines posteriorly, it was also lower, and the difference as compared with controls increased in a posterior direction up to the level of second premolars (up to 30%) and then slightly diminished (to 21% between the first molars). The reduction of area of transverse sections reached 45% between premolars and 39% between first molars. The palate in the anterior portion was highest on the cleft side and in a posterior direction the maximum height of the palate shifted toward the midline and even beyond that line toward the noncleft side. Palatal height did not depend on dentoalveolar arch width. CONCLUSION: The smaller width and height of the palate confirm the substantially reduced space for the tongue in patients with UCLP. The reduction is only slightly larger than in previously examined patients with isolated cleft palate. Palatal vault is asymmetrical, highest anteriorly on the cleft side and posteriorly on the noncleft side.

Adolescent↗

PubMed2003

Embryo-lethal and teratogenic effect of the new platinum compound DPR in pregnant mice.

Embryo-lethal and teratogenic effects caused by the cisplatin-procaine complex cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) were examined in CD-1 mice after a single administration of 7, 14, 21 or 28 mg/kg, injected on day 6, 9, 13 or 16 of pregnancy. At day 18 of pregnancy fetuses were removed and carefully examined for external, visceral and skeletal malformations under a dissecting microscope. A significant reduction of maternal weight gain was observed in pregnant mice after the administration of 21 (day 13) or 28 mg/kg (days 9 and 13) DPR. The exposure to DPR during the organogenesis and early histogenesis periods of prenatal development (administration on day 9 or 13) induced a significant reduction of the mean percentage of live fetuses and a significant increase of the mean percentage of dead and resorbed fetuses. A dose-dependent reduction of fetal body weight was observed in surviving specimens exposed to DPR on embryonic day 9, 13 or 16. The analysis of surviving fetuses killed on day 18 of gestation showed that a few, but statistically significant, external malformations and visceral anomalies were observed after administration of 21 or 28 mg/kg DPR on embryonic day 13. External malformations consisted of three hepato-omphalocele and six palatoschisis (one random palatoschisis was also observed at 21 mg/kg DPR given on day 9), while visceral anomalies included only renal pelvis dilatation. Skeletal anomalies affected fetuses independently of the day of treatment and were more frequent at the highest doses of DPR. They consisted of a delay in skull ossifications, vertebral and sternal anomalies, and formation of extra ribs. A low and non-significant incidence of skeletal malformations (asymmetric sternum) was noticed in fetuses. Our data demonstrated that DPR can cause embryotoxic effects if administered during the period of organogenesis and early histogenesis. Beside embryo-lethality, DPR induced growth retardation and malformations in surviving fetuses.

Abnormalities, Drug-Induced↗

PubMed2003

The developing mouse dentition: a new tool for apoptosis study.

Developing limb or differentiating neural and blood cells are traditional models used to study programmed cell death in mammals. The developing mouse dentition can also be an attractive model for studying apoptosis regulation. Apoptosis is most extant during early odontogenesis in mice. The embryonic tooth pattern is comprised not only of anlagen of functional teeth (incisor, molars), but also of vestiges of ancestral tooth primordia that must be suppressed. Apoptosis is involved in (a) the elimination of vestigial tooth primordia in the prospective toothless gap (diastema) between the incisor and molars and (b) the shaping of germs in functional teeth. This type of apoptosis occurs in the dental epithelium according to a characteristic temporo-spatial pattern. Where apoptosis concentrates, specific signaling is also found. We proposed a hypothesis to explain the stimulation of apoptosis in the dental epithelium by integrating two concepts: (1) The regulation of epithelial budding by positional information generated from interactions between growth-activating and growth-inhibiting signals, and (2) apoptosis stimulation by the failure of death-suppressing signals. During the budding of the dental epithelium, local excess in growth inhibitors (e.g., Bmps) might lead to the epithelial cells' failure to receive adequate growth-activating (apoptosis-suppressing) signals (e.g., Fgfs). The resulting signal imbalance leads to cell "suicide" by apoptosis. Understanding of apoptosis regulation in the vestigial tooth primordia can help to elucidate the mechanism of their suppression during evolution and to identify factors essential for tooth survival. The latter knowledge will be important for developing a technology of tooth engineering.

Animals↗

PubMed2003

Three-dimensional morphology of the palate in subjects with isolated cleft palate at the stage of permanent dentition.

OBJECTIVE: Three-dimensional analysis of palate size and shape in patients with isolated cleft palate at the stage of permanent dentition. DESIGN: Cross-sectional study using Fourier transform profilometry. SUBJECTS: Twenty-nine randomly selected dental casts of approximately 15-year-old boys with isolated cleft palate and 28 dental casts of normal boys of the same age. INTERVENTIONS: All patients were operated on by the same method (pushback and pharyngeal flap surgery) at a mean age of 4.5 years. MAIN OUTCOME MEASURES: Data on the palate height in 210 defined locations (pixels). RESULTS: The palate in isolated clefts is narrower throughout its whole extent and lower from the level of the first premolars. The difference, as compared with controls, increases in a posterior direction. At the level of the first molars, palatal height is reduced by one-quarter, the area of the transversal section by more than one-third. The shaping of the palate vault is, on average, symmetrical with a marked interindividual variability. Palatal height does not depend on the width of the dentoalveolar arch, and the height of the primary palate is not reduced. CONCLUSION: The smaller width and reduced height from the level of the first premolars posteriorly confirm the substantially reduced space available for the tongue in patients with isolated cleft palate. Deviations are on the average symmetrical, and the anterior part of the palate is not shallower.

Adolescent↗

PubMed2002

Asymmetrical morphogenesis and medio-lateral positioning of molars during mouse development.

The functionality of the dentition depends on occlusal relationships between opposing crown surfaces. To investigate the relative changes in positioning of upper and lower molar germs during mouse development, we used serial histological sections of late day 13 (embryonic day (ED)13.5) to early day 18 (ED18) foetus heads and performed computer-aided 3D reconstructions. From ED13.5 to ED15.5. the first lower molar (M1) got a less medial position relative to its upper counterpart (M1); superimposition progressed postero-anteriorly. From ED14.5, the apparent medial displacement of M(1) vs. M1 was partly due to the asymmetrical growth of the M(1) to give rise to the lingual row of cusps, conspicuous at ED17. The superimposition of M(2)/M2 along the medio-lateral axis was observed from their bud stage (ED14.5), and the one of M(1)/M1 was almost complete at ED15.5. However, this was not the final position. as at ED 18, M1 and M2 had a more lateral location than their upper counterparts. Immunostaining showed that differential expression of antigens associated to desmosomes but not to adherens junctions might be involved in the asymmetrical development of M(1) thus contributing to the relative medio-lateral positioning of the first molars at early stages.

Adherens Junctions↗

PubMed2002

Evolutionary implications of the occurrence of two vestigial tooth germs during early odontogenesis in the mouse lower jaw.

The study of closely-spaced developmental stages reveals the occurrence of three distinct dental segments during early odontogenesis in the ICR mouse lower jaw: the mesial (MS), the second rudimentary (R2), and the molar segments. At embryonic day (ED) 12.5, the MS displays an accessory bud, which regresses rapidly and disappears at ED 13.5. The R2 segment reaches a wide bud stage at ED 13.5 and then merges with the mesial end of the emerging first lower molar (M1) cap before ED 15.0. The MS and R2 segments never develop into functional teeth and are classified as vestigial tooth germs. Depending on their developmental chronology and on the position they occupy along the prospective mandibular tooth row, MS and R2 segments are putatively assigned to primordia of a third (dP3) and fourth (dP4) lower deciduous premolar, respectively. Evolutionary implications of these developmental data are discussed.

Animals↗

PubMedDate not supplied

Chernobyl: prenatal loss of four hundred male fetuses in the Czech Republic.

The long-standing higher male birth fraction is considered an indicator of reproduction stability and health. In contrast, a decrease in the male birth fraction has been reported after prenatal exposure to environmental chemical factors. There is generally higher vulnerability of boys to prenatal damage by environmental stress. We formulated a hypothesis that the Chernobyl disaster might also have had a greater negative impact on male than on female fetuses, leading to their selective loss and to a decrease in the male birth fraction. To test this hypothesis, we examined demographic data on monthly natality in the territory of the Czech Republic from 1950 to 1999. The male birth fraction was higher in the Czech Republic each month between 1950 and 1999 except November 1986, when it was significantly (P< 0.05) reduced. This finding suggests a selective negative effect of the Chernobyl accident on male fetuses during the 3rd month of prenatal development.

Abortion, Spontaneous↗