Jens Weingärtner

Is It Possible to Prevent Cleft Palate by Prenatal Administration of Folic Acid? An Experimental Study

OBJECTIVE In this study, folic acid was tested for its antiteratogenic effects on experimentally induced cleft palate in animals. DESIGN Eleven pregnant Lew 1 A dams (75 fetuses) received 200 mg/kg procarbazine via gastric tubing on postconception (p.c.) day 14 to induce a cleft palate (CP); seven of the pregnant dams (45 fetuses) were additionally given 4 mg/kg folic acid subcutaneously from the 14th to the 17th day p.c. As a control group, three more pregnant dams (24 fetuses) were not treated with the drugs mentioned above. All fetuses were delivered by Caesarian section on day 20 p.c. OUTCOMES MEASURED All fetuses were weighed and examined macroscopically with a stereomicroscope. Each fetal head was cut into 35 frontal sections and scrutinized histologically. RESULTS None of the control fetuses (n = 24) exhibited a cleft. Without folate administration, 90% of the fetuses (27 of 30) that received procarbazine exhibited a CP. After additional prenatal folate administration, this rate remained virtually unchanged (91%; 41 of 45). However, the proportion of complete (total) CP (4%) was significantly (p <.0001) lower than in the group without folate (53%). Cleft-associated microgenia and microglossia were also significantly less frequent when folate was administered prenatally: microgenia was reduced by 22% (p =.029) and microglossia by 24% (p =.032). CONCLUSIONS On the basis of these results, folate has a partial ameliorating effect on the teratogenicity of procarbazine given to pregnant rats. Additional studies are necessary on the effect of folate in different species, also taking cleft lip and CP into consideration.

Induction and Prevention of Cleft Lip, Alveolus and Palate and Neural Tube Defects with Special Consideration of B Vitamins and the Methylation Cycle

Previous studies on the development of cleft lip, alveolus, palate, and velum and neural tube defects have revealed several shared multifactorial causes. Both anomalies emerge at different times during embryonic development and are not associated with each other unless there is a genetic component to the etiology. Vitamin deficiency disorders are one of several factors contributing to the etiology of these anomalies.Vitamins B6, folic acid and B12 play an essential role in the methylation cycle. A lack of or deficiency in these vitamins thus has severe consequences for the organism, especially the unborn child. Due to its short half-life, vitamin B6 is particularly important for undisturbed embryogenesis and should be taken along with folic acid as a periconceptional supplement to prevent embryonic deformities.This paper is intended to provide the orthodontist (as a member of the interdisciplinary cleft team) with an overview of the issues and etiological significance of vitamin B deficiencies as possible inducers of these embryopathies. This may encourage comprehensive counselling, particularly of parents of children born with deformities who wish to have more children.ZusammenfassungBisherige Untersuchungen zur Entstehung von Lippen-Kiefer-Gaumen-Segel-Spalten und Neuralrohrdefekten brachten eine Reihe gemeinsamer multifaktorieller Ursachen zutage. Beide Fehlbildungen entstehen zu unterschiedlichen Zeitpunkten in der Embryonalentwicklung und treten unter Ausschluss genetischer Ursachen nicht assoziiert auf. Ätiologisch sind für die genannten Fehlbildungen neben anderen Ursachen auch Vitaminmangelstörungen von Bedeutung.Die Vitamine B6, Folsäure und B12 sind maßgeblich am Methylierungszyklus beteiligt. Ein Fehlen oder eine Unterversorgung dieser Vitamine hat somit schwerwiegende Folgen für den Organismus, insbesondere für das ungeborene Kind. Aufgrund einer kurzen Halbwertszeit hat das Vitamin B6 eine besondere Bedeutung für eine reibungslose Embryogenese und sollte deshalb neben Folsäure zusätzlich perikonzeptionell zur Prävention embryonaler Fehlbildungen verabreicht werden.Dem Kieferorthopäden im interdisziplinären Spaltteam soll mit dieser Arbeit eine Übersicht zur Problematik und ätiologischen Bedeutung von Vitamin-B-Mangelzuständen als mögliche Induktoren dieser Embryopathien gegeben werden. Damit bestünde die Möglichkeit einer umfassenden Beratung insbesondere von Eltern fehlgebildeter Kinder mit weiterem Kinderwunsch.

Functional 3-D analysis of patients with unilateral cleft of lip, alveolus and palate (UCLAP) following lip repair.

INTRODUCTION Particular importance is attached to lip repair cleft surgery, as numerous functional and aesthetic aspects have to be taken into account simultaneously. Spatial assessment of function and depiction of dynamic deviations is reasonable for describing surgical outcome in addition to long standing static analysis. This study aimed at 3D analysis of the oral area after reconstruction in patients with unilateral cleft lip, alveolus and palate. PATIENTS AND METHODS Twelve patients with unilateral cleft lip, alveolus and palate who underwent surgery according to Tennison-Randall were enrolled in this study. Soft tissue dynamics was analysed during passive stretching and active contraction of the lips, and photogrammetry was used for comparing relative changes of length and displacement vectors. The spatial coordinates of surgically significant and reproducible landmarks along the red-white lip junction were analyzed. RESULTS Static analysis of the lips revealed a good result with far-reaching symmetry in all cases. Regarding dynamic behaviour, two groups could be distinguished showing clear differences of passive distension and contraction behaviour. CONCLUSION Despite nominally identical surgical techniques and comparable static-morphological outcomes, dynamic analysis revealed differences pointing to a need for optimization.

Histological and histomorphometric study of growth-related changes of cranial sutures in the animal model

INTRODUCTION During the early development, numerous histological and morphometric changes occur in the cranial sutures the exact knowledge of which is of fundamental significance for understanding clinically relevant cranial anomalies. In this paper a histological and histomorphometric longitudinal study of the coronal, sagittal and lambdoid sutures in the rat is reported in relation to age. MATERIAL AND METHODS Forty-eight male Wistar rats (Rattus norvegicus Berkenhout) were raised under standard conditions. Eight animals each were sacrificed at defined time points (10, 14, 28, 42, 70, 98 days post partum) for specimen preparation. Histological preparations of the sagittal, coronal and lambdoid sutures were produced and examined morphologically and histomorphometrically (suture width, height, and area). RESULTS Histologically, three phases of sutural growth with characteristic structural features were found. Histomorphometry reveals a quasi linear increase in height from the 30th to the 98th day post partum. Suture width remained relatively constant in the area of dura mater and periosteum. CONCLUSION The sutures of the test animals studied had a similar growth behaviour primarily consisting of an increase in height with almost constant width. The three-phases of development could be demonstrated histologically in all sutures.

Effect of excessive methionine on the development of the cranial growth plate in newborn rats

OBJECTIVE Methionine is an essential amino acid and pivotal for normal growth and development. However, previous animal studies have shown that excessive maternal intake of methionine causes growth restrictions, organ damages, and abnormal growth of the mandible in newborn animals. However, the effect of excessive methionine on the development of the cranial growth plate is unknown. This study investigated histological alterations of the cranial growth plate induced by high methionine administration in newborn rats. DESIGN Twenty pregnant dams were divided into a control and an experimental group. The controls received a diet for rats and the experimental group was fed from the 18th gestational day with a special manufactured high methionine diet for rats. The high methionine diet was maintained until the end of the lactation phase (day 20). The offspring of both groups were killed at day 10 or 20 postnatally and their spheno-occipital synchondroses were collected for histological analysis. RESULTS The weight of the high-dose methionine treated experimental group was considerably reduced in comparison to the control group at day 10 and 20 postnatally. The cartilaginous area of the growth plate and the height of the proliferative zone were markedly reduced at postnatal day 10 in the experimental group. CONCLUSIONS In summary, the diet-induced hypermethioninemia in rat dams resulted in growth retardations and histomorphological changes of the spheno-occipital synchondrosis, an important craniofacial growth centre in newborns. This finding may elucidate facial dysmorphoses reported in patients suffering from hypermethioninemia.

Development dependent collagen gene expression in the rat cranial base growth plate.

The spheno-occipital synchondrosis is part of the cranial base growth plate and is of crucial importance in craniofacial development. In this investigation, we studied changes in collagen gene expression in the spheno-occipital synchondrosis in order to identify the developmental stages most important for extracellular matrix production and ossification of the rat cranial base growth plate. Gene transcripts of type II and X collagen were most abundant at day 10 postnatally in the spheno-occipital synchondrosis. This observation is assumed to be due to intrinsic genetic factors and local environmental factors.

The role of apoptosis in early embryonic development of the adenohypophysis in rats

BackgroundApoptosis is involved in fundamental processes of life, like embryonic development, tissue homeostasis, or immune defense. Defects in apoptosis cause or contribute to developmental malformation, cancer, and degenerative disorders.MethodsThe developing adenohypophysis area of rat fetuses was studied at the embryonic stage 13.5 (gestational day) for apoptotic and proliferative cell activities using histological serial sections.ResultsA high cell proliferation rate was observed throughout the adenohypophysis. In contrast, apoptotic cells visualized by evidence of active caspase-3, were detected only in the basal epithelial cones as an introducing event for fusion and closure of the pharyngeal roof.ConclusionWe can clearly show an increasing number of apoptotic events only at the basic fusion sides of the adenohypophysis as well as in the opening region of this organ. Apoptotic destruction of epithelial cells at the basal cones of the adenohypophysis begins even before differentiation of the adenohypophyseal cells and their contact with the neurohypophysis. In early stages of development, thus, apoptotic activity of the adenohypophysis is restricted to the basal areas mentioned. In our test animals, the adenohypophysis develops after closure of the anterior neuroporus.

Profiling type I collagen gene expression in growing mandibular structures

We conducted a temporal gene expression analysis with type I collagen in the coronoid process, alveolar process and mandibular angle of the rat. We observed gene expression cross-sectionally across different important physiological time points in the rat postnatal life in order to observe in which developmental stage mandibular development mainly occur. This study indicates prominent type I collagen expression at day 10 postpartum in the mandibular ramus and at day 21 in the alveolar process. These findings correspond well with previously obtained data from proliferation studies in facial bone suggesting that craniofacial growth in the rat occurs mainly between days 10 and 21.