Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished monkeys

Undernutrition elicited by a low-protein diet determines a marked reduction of hypophyseal activity and affects the function of the respective target organs. The objective of the present investigation was to study the ultrastructural and quantitative immunohistochemical changes of the different pituitary cell populations in undernourished monkeys that had been previously shown to have significant changes in craniofacial growth. Twenty Saimiri sciureus boliviensis monkeys of both sexes were used. The animals were born in captivity and were separated into two groups at one year of age, i.e., control and undernourished animals. The monkeys were fed ad libitum a 20% (control group) and a 10% (experimental group) protein diet for two years. Pituitaries were processed for light and electron microscopy. The former was immunolabeled with anti-GH, -PRL, -LH, -FSH, -ACTH, and -TSH sera. Volume density and cell density were measured using an image analyzer. Quantitative immunohistochemistry revealed a decrease in these parameters with regard to somatotrophs, lactotrophs, gonadotrophs and thyrotrophs from undernourished animals compared to control ones. In these populations, the ultrastructural study showed changes suggesting compensatory hyperfunction. On the contrary, no significant changes were found in the morphometric parameters or the ultrastructure of the corticotroph population. We conclude that in undernourished monkeys the somatotroph, lactotroph, gonadotroph, and thyrotroph cell populations showed quantitative immunohistochemical changes that can be correlated with ultrastructural findings.

Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.

Neonatal administration of citalopram delays somatic maturation in rats

We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9% NaCl, w/v, sc). Compared to saline, body weight was lower (24.04%, P < 0.01) for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19%, P < 0.01). Tail length was reduced in the Cit20 group (15.48%, P < 0.001) from the 8th to the 21st day. A reduction in mediolateral head axis (10.53%, P < 0.05) was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16%, P < 0.001). A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28%, P < 0.05) from the 13th to the 21stday. Conversely, this axis showed accelerated growth from the 12th to the 21stday in the Cit5 group (13.05%, P < 0.05). Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

Reduced folate carrier 1 (RFC1) is associated with cleft of the lip only

In this report, we have reanalyzed genotyping data in a collection of families from South America based on maternal origin. Genotyping analysis was performed at the Craniofacial Anomalies Research Center at the University of Iowa. These genotypes were derived from genomic DNA samples obtained from blood spots from children born with isolated orofacial clefts in 45 hospitals located in eight countries (Argentina, Bolivia, Brazil, Chile, Ecuador, Paraguay, Uruguay, and Venezuela) collaborating with ECLAMC (Latin American Collaborative Studies of Congenital Malformations) between January 1998 and December 1999. Dried blood samples were sent by regular mail to the Laboratory of Congenital Malformations, Federal University of Rio de Janeiro. Previous findings suggested that mitochondrial haplotype D is more commonly found among cleft cases born in South America. We hypothesized that association of certain genes may depend upon the ethnic origin, as defined by population-specific markers. Therefore, we tested if markers in MTHFR (5,10-methylenetetrahydrofolate reductase) and RFC1 (reduced folate carrier 1) were associated with oral clefts, depending on the maternal origin defined by the mitochondrial haplotype. Transmission distortion of alleles in MTHFR C677T and RFC1 G80A polymorphic variants was tested in 200 mother/affected child pairs taking into consideration maternal origin. RFC1 variation was over-transmitted to children born with cleft lip only (P = 0.017) carrying mitochondrial DNA haplotypes other than haplotype D. Our results provide a new indication that variation in RFC1 may contribute to cleft lip only. Future studies should investigate the association between oral clefts and RFC1 based on more discrete phenotypes.

Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants.

Evaluation of the immune humoral response of Brazilian patients with Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental and growth deficiency, and recurrent respiratory infections. RTS has been associated with CREBBP gene mutations, but EP300 gene mutations have recently been reported in 6 individuals. In the present study, the humoral immune response in 16 RTS patients with recurrent respiratory infections of possible bacterial etiology was evaluated. No significant differences between patients and 16 healthy controls were detected to explain the high susceptibility to respiratory infections: normal or elevated serum immunoglobulin levels, normal salivary IgA levels, and a good antibody response to both polysaccharide and protein antigens were observed. However, most patients presented high serum IgM levels, a high number of total B cell and B subsets, and also high percentiles of apoptosis, suggesting that they could present B dysregulation. The CREBBP/p300 family gene is extremely important for B-cell regulation, and RTS may represent an interesting human model for studying the molecular mechanisms involved in B-cell development.

MSX1 gene and nonsyndromic oral clefts in a Southern Brazilian population

Nonsyndromic oral clefts (NSOC) are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp), 0.169 (173 bp), 0.096 (171 bp) and 0.67 (169 bp). A transmission disequilibrium test with a family-based association test (FBAT) software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005). These results suggest that the CA repeat polymorphism of theMSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.

Longitudinal evaluation of sleep-related breathing disorders in an orthodontic population

Introduction: Les troubles respiratoires du sommeil (TRS), qui représentent une préoccupation croissante pour la santé, ont des effets significatifs sur la santé, le comportement et la performance académique chez l’enfant. Les malformations craniofaciales, l’hypertrophie adéno-amygdalienne et l'obésité, représentent des facteurs de risque importants dans le développement de cette condition. Les symptômes des TRS ont été étudiés dans une étude prospective chez les enfants et adolescents durant leur traitement orthodontique dans un milieu universitaire. Cette étude a cherché à décrire la prévalence et les facteurs de risque principaux des TRS, ainsi que l'impact des différentes interventions orthodontiques sur les symptômes TRS. Matériel et méthodes: dans une étude cohorte prospective, un groupe de 168 sujets âgés de 12 à 21 ans ont été soumis, quatre ans après la prise de données initiale, à un examen craniofacial en plus d'être administré des questionnaires qui ont recueilli des données sur la situation socio-démographique, le bruxisme et les troubles d’ATM, le sommeil et le comportement diurne, et les facteurs neuropsychologiques. Résultats: l'indice de masse corporelle a été augmenté mais est demeurée dans la même catégorie aux deux moments de l'enquête. Il ya eu une augmentation du serrement des dents et des symptômes de l'ATM, une diminution de la taille des amygdales, et une augmentation de la somnolence diurne. La prévalence des TRS n'a pas changé entre l’étude initiale et l’étude de suivi. Aucune intervention orthodontique s'est avérée avoir un effet cliniquement significatif sur les voies aériennes supérieures. Conclusions: la prévalence des symptômes TRS était constante par rapport aux valeurs de base pour la population étudiée, mais a augmenté si rapportée à la population générale. Les traitements orthodontiques ne montrent aucun effet sur les TRS. Mots-clés : apnée du sommeil, craniofacial, prévalence, ronflement, traitement orthodontique, voies aériennes supérieures

Étude rétrospective des malocclusions dento-squelettiques associées à la scaphocéphalie

Introduction : La scaphocéphalie est la craniosynostose monosuturaire la plus commune (1/2000). Celle-ci est causée par la fusion prématurée de la suture sagittale. Une chirurgie corrective de la voûte crânienne peut être effectuée dans la première année de vie de l’enfant. Il n’existe actuellement aucune donnée précise dans la littérature scientifique étudiant l’occlusion chez les patients scaphocéphales, ainsi que les impacts potentiels de la chirurgie de la voûte crânienne sur celle-ci. Objectifs : L’objectif primaire de cette étude est de décrire et comparer la malocclusion dento-squelettique d’un groupe de patients scaphocéphales à une population pédiatrique normale. L’objectif secondaire est d’évaluer la différence au niveau de l’occlusion entre un sous-groupe de patients scaphocéphales ayant eu une chirurgie corrective de la voûte crânienne et un sous-groupe ne l’ayant pas eu. Méthodologie : Quatre-vingt-onze patients scaphocéphales (2-11 ans; 71 garçons) de la banque de données de la Clinique de Craniofacial du CHU Ste-Justine ont formé le groupe expérimental. Tous les patients ont eu un examen orthodontique complet et ont été suivis. Parmi ceux-ci, quarante-quatre avaient eu une chirurgie corrective de la voûte crânienne et quarante-sept n’en avaient pas eu, mais étaient suivis régulièrement à la clinique. Trente-huit (33 garçons; 17 opérés) de ces patients ont eu des radiographies céphalométriques latérales et parmi ceux-ci, un certain nombre ont reçus des suivis de croissance radiologiques. Résultats : Les valeurs cliniques de la classification dentaire, ainsi que la mesure du surplomb horizontal, ont indiqué une augmentation de la prévalence de malocclusions de classe II chez les enfants scaphocéphales. Par contre, les valeurs céphalométriques indicatrices de malocclusion squelettique de classe II (ex. : N-A perp HP, N-B perp HP, N-Pog perp HP, Wits, N-A-Pog) sont demeurées dans les limites de la normale. Certaines valeurs céphalométriques présentent une différence statistiquement significative entre les patients opérés et non opérés (ANS-PNS t2, p=0.025; /1-FH t2, p=0.028), mais ces variations individuelles ne sont pas reliées à la scaphocéphalie. Conclusion : Les enfants scaphocéphales présentent cliniquement davantage de malocclusions de classe II que les enfants normaux. Par contre, les valeurs radiologiques antéro-postérieures et transverses demeurent dans les limites de la normale. La chirurgie corrective de la voûte crânienne n’affecte également pas l’occlusion chez ces patients.

L’effet du port nocturne des prothèses complètes sur le sommeil et la qualité de vie liée à la santé buccodentaire : une étude pilote expérimentale

Problématique : L’édentement et les troubles du sommeil sont des affections chroniques fréquentes chez les personnes âgées et qui peuvent avoir des conséquences défavorables sur le bien-être de ces personnes, ainsi que sur leur qualité de vie. L’édentement pourrait perturber le sommeil par la modification de la structure crânio-faciale et des tissus mous environnants. Cependant, cette relation n'est pas suffisamment documenté. Objectifs : Le but de cette étude pilote était de préparer la mise en œuvre d’une étude clinique randomisée contrôlée concernant l’effet du port nocturne des prothèses complètes sur la qualité du sommeil. Méthodologie : Treize aînés édentés ont participé à cette étude clinique randomisée contrôlée de type croisé. L’intervention consistait à dormir avec ou sans les prothèses durant la nuit. Les participants à l'étude ont été assignés à porter et ne pas porter leurs prothèses dans des ordres alternatifs pour des périodes de 30 jours. La qualité du sommeil a été évaluée par la polysomnographie portable et le questionnaire Pittburgh Sleep Quality Index (PSQI). Les données supplémentaires incluent la somnolence diurne, évaluée par le questionnaire Epworth Sleepiness Scale (ESS), et la qualité de vie liée à la santé buccodentaire, évaluée par le questionnaire Oral Health Impact Profile 20 (OHIP-20). De plus, à travers les examens cliniques et radiologiques, les données des caractéristiques sociodémographiques, de la morphologie oropharyngée, des caractéristiques buccodentaires et des prothèses ont été recueillies. Les modèles de régression linéaire pour les mesures répétées ont été utilisés pour analyser les résultats. Résultats : L’étude de faisabilité a atteint un taux de recrutement à l’étude de 59,1% et un taux de suivi de 100%. Le port nocturne des prothèses dentaires augmentait l’index d'apnée-hypopnée (IAH) et le score PSQI par rapport au non port nocturne des prothèses : (IAH : Médiane = 20,9 (1,3 - 84,7) versus 11,2 (1,9 - 69,6), p = 0,237; le score PSQI : Médiane = 6,0 (3,0 - 11,0) versus 5,0 (1,0 - 11,0), p = 0,248). Cependant, ces différences n'étaient pas statistiquement significatives, sauf que pour le temps moyen d’apnée (plus long avec des prothèses) (p < 0,005) et le temps de ronflement relatif (moins élevé avec des prothèses) (p < 0,05). La somnolence diurne excessive et la qualité de vie liée à la santé buccodentaire étaient semblables pour les deux interventions (le score ESS : Médiane = 4,0 (3,0-10,0) versus 5,0 (2,0-10,0), p = 0,746; le score OHIP-20: Médiane = 31,0 (20,0-64,0) versus 27,0 (20,0-49,0), p = 0,670). L’impact néfaste du port nocturne des prothèses complètes sur le sommeil a été statistiquement significatif chez les personnes souffrant de l’apnée-hypopnée moyenne à sévère (p < 0,005). Conclusion : L’essai clinique pilote a montré que le port nocturne des prothèses complètes a un impact négatif sur la qualité du sommeil des gens âgés édentés, surtout chez les personnes avec l’apnée obstructive du sommeil modérée à sévère. Les résultats doivent être confirmés par l’étude clinique randomisée contrôlée de phase II.

Uso de la Hibridación Genómica Comparativa-Array (HGC-a) en pacientes con retraso global del desarrollo y fenotipo particular. Revisión sistemática de la literatura

Introducción: la hibridación genómica comparativa en una técnica que permite la exploración de las anormalidades cromosómicas. Su utilidad en la aproximación de los pacientes con retraso global del desarrollo o fenotipo dismórfico, sin embargo, no ha sido explorada mediante una revisión sistemática de la literatura. Metodología: realizó una revisión sistemática de la literatura. Se incluyeron estudios controlados, cuasi-experimentales, de cohortes, de casos y controles, transversales y descriptivos publicados en idiomas inglés y español entre los años 2000 y 2013. Se realizó un análisis de la evidencia con un enfoque cualitativo y cuantitativo. Se realizó un análisis del riesgo de sesgo de los estudios incluidos. Resultados: se incluyeron 4 estudios que cumplieron con los criterios de inclusión. La prevalencia de alteraciones cromosómicas en los niños con retraso global del desarrollo fue de entre el 6 y 13%. El uso de la técnica permitió identificar alteraciones que no fueron detectadas mediante el cariotipo. Conclusiones: la hibridación genómica comparativa es una técnica útil en la aproximación diagnóstica de los niños con retraso global del desarrollo y del fenotipo dismórfico y permite una mayor detección de alteraciones comparada con el cariotipo.

Alteraciones respiratorias durante el sueño en niños con Síndrome Down a la altura de Bogotá

Objetivo: determinar la frecuencia de las diferentes alteraciones respiratorias durante el sueño (ARS) e hipertensión pulmonar (HTP) y establecer la saturación de oxígeno (SpO2) en vigilia, sueño y durante los eventos en niños con Síndrome Down (SD) a la altura de Bogotá (2640m) de acuerdo a grupos de edad e IMC. Métodos: estudio descriptivo de corte transversal, se incluyeron todos los niños con SD con sospecha de ARS remitidos a polisonograma (PSG) de octubre de 2011 a enero de 2013 a la Fundación Neumológica Colombina (FNC). Se dividieron en 3 grupos: apnea obstructiva, apnea obstructiva y central, sin apneas. Resultados: 74 niños, el 36,5% mujeres, edad media 4 años. 47,3% presento apnea obstructiva, más frecuente en >2 años, 35,1% apnea obstructiva y central, más frecuente en < 2 años y 17,6 % sin apnea. SpO2 promedio en apnea obstructiva 84,63%, apnea obstructiva y central: 81,8% y sin apnea: 86,85% (p 0,058). 23% presento obesidad, 16% con apnea obstructiva. 53 pacientes tenían ecocardiograma: 28% HTP, 53,3% tuvo apnea obstructiva y 26,7 apnea obstructiva y central, no diferencias significativas. SpO2 promedio en HTP 88,3% vigilia, 86,2% sueño REM, 85,7 % sueño no REM, no diferencia significativa comparada con pacientes sin HTP. Conclusiones: Las ARS son frecuentes en los niños con SD, La desaturación está presente en los niños con SD independiente del tipo de apnea. A todos los niños SD se les debe practicar un PSG en el primer año de vida.

Evaluación de la vía aérea superior en pacientes con sahos mediante cefalometría 3D y multiplanar

Objetivo: determinar parámetros biométricos para evaluación y diagnóstico de pacientes con SAHOS por medio de Cefalometría Tridimensional y reconstrucción Multiplanar escanográfica. Materiales y Métodos: se realizó estudio observacional tipo cross-sectional, con 25 pacientes diagnosticados con SAHOS, a los cuales se les hizo TAC simple de cara con reconstrucción multiplanar y tridimensional, evaluando volumen de vía aérea, longitud, promedio del área en corte transversal, área retropalatal, área reglosal, espacio retrogloso lateral y anteroposterior. Resultados: se incluyeron 25 pacientes y realizaron medidas de volumen, longitud, promedio del área en corte transversal, área retropalatal, área retroglosal y espacios regloso lateral y anteroposterior, realizando análisis estadístico mediante el programa SPSS 17.0 reportando medidas de tendencia central como promedio, media, moda, rango, desviación estándar, y concordancia inter e intra observador. Conclusión: la Cefalometría tridimensional con reconstrucción multiplanar ha mostrado ser un excelente método de evaluación de vía aérea en pacientes con SAHOS, obteniendo propias clasificaciones dentro del estudio de estos pacientes. Sin embargo, ante la escasa literatura y difícil obtención de parámetros de referencia es necesario promover el estudio y la investigación de este método diagnostico en pacientes con SAHOS.

Newborn hearing screening: examining the presence of risk factors for hearing loss

This paper identifies risk factors associated with hearing loss in newborns, including family history, craniofacial abnormalities, and ototoxic medications.

The role of Wnt signalling in the development of somites and neural crest

The Wnt family of secreted signalling molecules controls a wide range of developmental processes in all metazoans. In this investigation we concentrate on the role that members of this family play during the development of (1) the somites and (2) the neural crest. (3) We also isolate a novel component of the Wnt signalling pathway called Naked cuticle and investigate the role that this protein may play in both of the previously mentioned developmental processes. (1) In higher vertebrates the paraxial mesoderm undergoes a mesenchymal-to-epithelial transformation to form segmentally organised structures called somites. Experiments have shown that signals originating from the ectoderm overlying the somites or from midline structures are required for the formation of the somites, but their identity has yet to be determined. Wnt6 is a good candidate as a somite epithelialisation factor from the ectoderm since it is expressed in this tissue. In this study we show that injection of Wnt6-producing cells beneath the ectoderm at the level of the segmental plate or lateral to the segmental plate leads to the formation of numerous small epithelial somites. We show that Wnts are indeed responsible for the epithelialisation of somites by applying Wnt antagonists which result in the segmental plate being unable to form somites. These results show that Wnt6, the only member of this family to be localised to the chick paraxial ectoderm, is able to regulate the development of epithelial somites and that cellular organisation is pivotal in the execution of the differentiation programmes. (2) The neural crest is a population of multipotent progenitor cells that arise from the neural ectoderm in all vertebrate embryos and form a multitude of derivatives including the peripheral sensory neurons, the enteric nervous system, Schwann cells, pigment cells and parts of the craniofacial skeleton. The induction of the neural crest relies on an ectodermally derived signal, but the identity of the molecule performing this role in amniotes is not known. Here we show that Wnt6, a protein expressed in the ectoderm, induces neural crest production. (3) The intracellular response to Wnt signalling depends on the choice of signalling cascade activated in the responding cell. Cells can activate either the canonical pathway that modulates gene expression to control cellular differentiation and proliferation, or the non-canonical pathway that controls cell polarity and movement (Pandur et al. 2002b). Recent work has identified the protein Naked cuticle as an intracellular switch promoting the non-canonical pathway at the expense of the canonical pathway. We have cloned chick Naked cuticle-1 (cNkd1) and demonstrate that it is expressed in a dynamic manner during early embryogenesis. We show that it is expressed in the somites and in particular regions where cells are undergoing movement. Lastly our study shows that the expression of cNkd1 is regulated by Wnt expression originating from the neural tube. This study provides evidence that non-canonical Wnt signalling plays a part in somite development.