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1.
Mol Med Rep ; 22(4): 2925-2931, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945398

RESUMO

Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4­month­old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three­generation family were subsequently collected, and whole­exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole­transcriptome sequencing, expression analysis and Gene Ontology enrichment analysis were conducted on two groups of patients with phenotypic diversity from the same family. These analyses identified significant differentially expressed genes and enriched pathways in these two groups. Altogether, these findings provide insight into the mechanism underlying the variable expressivity of VWS.


Assuntos
Anormalidades Múltiplas/genética , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Características da Família , Fatores Reguladores de Interferon/genética , Lábio/anormalidades , Mutação de Sentido Incorreto , Polimorfismo Genético , Anormalidades Múltiplas/sangue , Adulto , Anodontia/sangue , Anodontia/complicações , Anodontia/genética , Criança , Pré-Escolar , China , Fenda Labial/sangue , Fenda Labial/complicações , Fissura Palatina/sangue , Fissura Palatina/complicações , Cistos/sangue , Cistos/complicações , Éxons , Feminino , Humanos , Lactente , Fatores Reguladores de Interferon/sangue , Masculino , Anamnese , Pessoa de Meia-Idade , Linhagem , Fenótipo , Transcriptoma
2.
Immunol Med ; 43(3): 130-134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32511082

RESUMO

The aim of the work was a comprehensive assessment of the cytokine system and peripheral blood osteocalcin with the establishment of features of their interconnections in children with congenital cleft lip and palate (CCLP) in comparison with corresponding controls at different age periods. Levels of IL17, IL4, IL6, IL1ß, IFNγ and osteocalcin were analyzed by enzyme immunoassay in the peripheral blood of 80 children (0-12 months, 1-3 years, 4-9 years, 10-15 years) with CCLP and age-appropriate control of healthy individuals (40 people). An analysis of the obtained data shows that in children with CCLP we revealed significant differences between pro-inflammatory (IL1ß, IL6, IL17), regulatory (IFNγ), anti-inflammatory (IL4) cytokines and osteocalcin compared with controls. Differences were found in the content of IL17, IFNγ, IL4 and osteocalcin in healthy children and in children with CCLP in postnatal ontogenesis. Cytokine deregulation of immunosteogenesis in CCLP, leading to a significant deficit of osteocalcin in the first year of life due to imbalance of the cytokine profile: discordant IL17, IFNγ and IL4 were detected. Obtained data are undoubtedly important in the future for developing new strategies for targeted therapy aimed at normalizing osteocalcin levels at different age periods in children with CCLP.


Assuntos
Fenda Labial/imunologia , Fissura Palatina/imunologia , Citocinas/sangue , Mediadores da Inflamação/sangue , Osteocalcina/sangue , Osteogênese/imunologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Fenda Labial/sangue , Fenda Labial/fisiopatologia , Fissura Palatina/sangue , Fissura Palatina/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-1beta , Interleucina-4/sangue , Interleucina-6/sangue , Masculino
3.
Mol Med Rep ; 20(1): 513-528, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115538

RESUMO

Non­syndromic orofacial clefts (NSOC), which include cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), are common congenital birth defects in humans. Accumulating evidence indicates that long non­coding RNAs (lncRNAs) and microRNAs (miRNAs or miRs) play important roles in NSOC; however, the potential regulatory associations between them remain largely unknown. In this study, we performed next­generation RNA sequencing (RNA­seq) to identify transcriptome profiles, including mRNAs, lncRNAs and miRNAs, in patients with CL/P and CPO. A total of 36 lncRNAs, 1,341 mRNAs and 60 miRNAs were found to be differentially expressed in the CL/P group compared to the control group, and 57 lncRNAs, 1,255 mRNAs and 162 miRNAs were found to be differentially expressed in the CPO group compared to the control group. Subsequently, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to validate the expression of selected lncRNAs, miRNAs and mRNAs. In addition, bioinformatics methods were employed to explore the potential functions of ncRNAs and to construct lncRNA­miRNA­mRNA regulatory networks. To the best of our knowledge, this is the first study to comprehensively analyze regulated non­coding RNAs (ncRNAs) in CL/P and CPO, providing a novel perspective on the etiology of NSOC and laying the foundation for future research into the potential regulatory mechanisms of ncRNAs and mRNAs in NSOC.


Assuntos
Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Encéfalo/patologia , Pré-Escolar , Fenda Labial/sangue , Fenda Labial/patologia , Fissura Palatina/sangue , Fissura Palatina/patologia , Biologia Computacional , Feminino , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , MicroRNAs/sangue , RNA Longo não Codificante/sangue , RNA Mensageiro/sangue , RNA Mensageiro/genética , Transcriptoma/genética
4.
Mol Med Rep ; 19(5): 3831-3840, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896870

RESUMO

Congenital heart disease (CHD), and cleft lip and palate (CLP) are currently the most common types of structural malformation in infants. Various methods have been used to identify the disease­associated genes. However, targeted next­generation sequencing (NGS) is not yet considered an option for routine use. Thus, the present study aimed to assess the safety and feasibility of using targeted NGS in patients with CHD concomitant with CLP. Between November 2015 and May 2017, a total of 17 patients with CHD concomitant with CLP, who were excluded from a diagnosis of trisomy syndrome, were selected at The Second Xiangya Hospital of Central South University (Changsha, China). Genomic DNA was extracted from peripheral blood samples of the patients. The copy number variants (CNVs) were determined by conducting a single nucleotide polymorphism (SNP) array with Illumina HumanOmni1­Quad Beadchip, while information on other gene mutations was obtained from targeted sequencing. The functions of gene mutations were then predicted using the PolyPhen­2, SIFT and Mutation Taster tools. Finally, Sanger sequencing was used to verify the mutations. The results identified no pathogenic mutations in CNVs analyzed by high­throughput SNP sequencing. Targeted NGS results demonstrated that 10 patients (58.8%) carried gene mutations, including 4 (23.5%) genetically diagnosed cases and 6 (35.3%) cases with unknown etiology. The 4 known diseases were Opitz G/BBB syndrome caused by MID1 gene mutation, Loeys­Dietz syndrome caused by TGFBR1 gene mutation, Ritscher­Schinzel/3C syndrome caused by KIAA0196 gene mutation and CHARGE syndrome caused by CHD7 gene mutation. The remaining 6 cases were not genetically diagnosed, although they carried candidate genes. In conclusion, the present study demonstrated that targeted NGS was an effective and accurate candidate gene detection method in patients with CHD concomitant with CLP.


Assuntos
Biomarcadores/sangue , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Cardiopatias Congênitas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , Criança , Pré-Escolar , Fenda Labial/sangue , Fenda Labial/complicações , Fenda Labial/genética , Fissura Palatina/sangue , Fissura Palatina/complicações , Fissura Palatina/genética , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/genética , Humanos , Lactente , Masculino
5.
Medicine (Baltimore) ; 97(25): e11224, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924053

RESUMO

BACKGROUND: Orofacial clefts include cleft lip only (CLO), cleft palate only (CPO), and cleft lip with palate (CLP). Previously, we reported the expression profile of plasma microRNAs in CLO, CPO, and CLP, respectively. However, the interaction of each subtype remains poorly investigated. METHODS: In this study, we integrated the expression profiles of plasma miRNAs in these 3 subtypes, and assessed the distinct and overlapping dysregulated miRNAs using Venn diagrams. Their respective target genes reported in the literature were further analyzed using pathway analysis. RESULTS AND CONCLUSION: The results showed that distinct or overlapping signaling pathways were involved in CLO, CPO, and CLP. The common key gene targets reflected functional relationships to the Wnt, Notch, TGF-beta, and Hedgehog signaling pathways. Further studies should examine the mechanism of the potential target genes, which may provide new avenues for future clinical prevention and therapy.


Assuntos
Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , MicroRNAs/sangue , MicroRNAs/genética , Fenda Labial/sangue , Fenda Labial/classificação , Fissura Palatina/sangue , Fissura Palatina/classificação , Epigênese Genética/genética , Humanos , Análise em Microsséries/métodos , Transdução de Sinais/genética
6.
Birth Defects Res ; 110(6): 495-501, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29316356

RESUMO

BACKGROUND: Previous studies have reported an association between maternal zinc deficiency and increased risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring. A high prevalence of zinc deficiency and a high prevalence of NSCL/P have been reported in Ecuador. We postulated that mothers of infants with NSCL/P may have lower serum zinc levels than women from the general population. METHODS: A case series study was conducted from November 2013 to July 2016. Thirty-five healthy mothers of infants with NSCL/P were selected during surgical missions conducted by Operación Sonrisa Ecuador. A single blood sample along with pertinent medical history was collected during personal interviews after 3.6 months postpartum. The prevalence of plasma zinc concentration (PZn) deficiency among the participants was determined and analyzed along with the prevalence of PZn deficiency in Ecuadorian women of reproductive age from the general population. RESULTS: The mean PZn was 11.47 µmol/dm3 . The prevalence of PZn deficiency among the participants was 31.4% (95% CI: 17.1-48.6) and differed significantly from the prevalence of zinc deficiency observed among women from the general population (G2 = 8.66; p < .05). CONCLUSIONS: The results showed that the prevalence of PZn deficiency is lower in a cohort of healthy mothers of infants with NSCL/P than in women from the general population in Ecuador. More studies are required to confirm these findings and evaluate other factors related to NSCL/P pathophysiology in the Ecuadorian population.


Assuntos
Fenda Labial/sangue , Fissura Palatina/sangue , Mães , Zinco/sangue , Equador , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
7.
Laryngoscope ; 127(10): E336-E339, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28543373

RESUMO

OBJECTIVES/HYPOTHESIS: A candidate variant (p.Val496Ala) of the ACSS2 gene (T > C missense, rs59088485 variant at chr20: bp37 33509608) was previously found to consistently segregate with nonsyndromic cleft lip and/or palate (NSCLP) in three Honduran families. Objectives of this study were 1) to investigate the frequency of this ACSS2 variant in Honduran unrelated NSCLP patients and unrelated unaffected controls and 2) to investigate the frequency of this variant in Colombian unrelated affected NSCLP patients and unrelated unaffected controls. STUDY DESIGN: Case-control studies. METHODS: Sanger sequencing of 99 unrelated Honduran NSCLP patients and 215 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. Sanger sequencing of 230 unrelated Colombian NSCLP patients and 146 unrelated unaffected controls for the p.Val496Ala ACSS2 variant was used to determine the carrier frequency in NSCLP patients and controls. RESULTS: In the Honduran population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 4.0 (P = .03), with a carrier frequency of seven of 99 (7.1%) in unrelated affected and four of 215 (1.9%) in unrelated unaffected individuals. In the Colombian population, the odds ratio of having NSCLP among carriers of the p.Val496Ala ACSS2 variant was 2.6 (P = .04), with a carrier frequency of 23 of 230 (10.0%) in unrelated affected and six of 146 (4.1%) in unrelated unaffected individuals. CONCLUSIONS: These findings support the role of ACSS2 in NSCLP in two independent Hispanic populations from Honduras and Colombia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E336-E339, 2017.


Assuntos
Acetato-CoA Ligase/genética , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Acetato-CoA Ligase/sangue , Estudos de Casos e Controles , Pré-Escolar , Fenda Labial/sangue , Fissura Palatina/sangue , Colômbia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Honduras , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos
8.
Oncotarget ; 7(52): 86266-86279, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27863433

RESUMO

Plasma microRNAs (miRNAs) have recently emerged as a new class of regulatory molecules that influence many biological functions. However, the expression profile of plasma microRNAs in nonsyndromic cleft palate (NSCP) or nonsyndromic cleft lip with cleft palate (NSCLP) remains poorly investigated. In this study, we used Agilent human miRNA microarray chips to monitor miRNA levels in three NSCP plasma samples (mixed as the CP group), three NSCLP plasma samples (mixed as the CLP group) and three normal plasma samples (mixed as the Control group). Six selected plasma miRNAs were validated in samples from an additional 16 CP, 33 CLP and 8 healthy children using qRT-PCR. Using Venn diagrams, distinct and overlapping dysregulated miRNAs were identified. Their respective target genes were further assessed using gene ontology and pathway analysis. The results show that distinct or overlapping biological processes and signalling pathways were involved in CP and CLP. Our study showed that the common key gene targets reflected functional relationships to the Notch, Wnt, phosphatidylinositol and Hedgehog signalling pathways. Further studies should examine the mechanism of the potential target genes, which may provide new avenues for future clinical prevention and therapy.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , MicroRNAs/sangue , Fenda Labial/sangue , Fissura Palatina/sangue , Feminino , Ontologia Genética , Humanos , Lactente , Masculino , MicroRNAs/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
9.
Biomed Pharmacother ; 82: 459-66, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27470385

RESUMO

OBJECTIVE: The aim of this study was to determine the expression profile of plasma microRNAs in nonsyndromic cleft lip (NSCL) and their clinical significance as biomarkers. METHODS: Agilent human miRNA microarray chips were used to analyze three NSCL plasma samples (mixed as CL group) and three normal plasma samples (mixed as Control group). Six selected plasma miRNAs were validated using qRT-PCR between another 13 CL and 11 healthy children. The receiver operating characteristic (ROC) curve analysis was applied for three elevated miRNAs, miR-16-2-3p, miR-365a-3p and miR-877-5p. Their target genes were further assessed using gene ontology and pathway analysis. RESULTS: The plasma miRNA differentially expressed (fold change ≥2) amounted to 305. In particular, it had been validated that miR-16-2-3p, miR-365a-3p and miR-877-5p were elevated in NSCL plasma samples. ROC curve analysis revealed that each microRNA was able to significantly discriminate NSCL subjects from normal controls. Gene ontology and pathway analysis revealed that many processes over-represented in CL are related to system development process, regulation of nitrogen compound metabolic process, FoxO signaling pathway and the ErbB signaling pathway. CONCLUSION: Our study demonstrated that plasma miR-16-2-3p, miR-365a-3p and miR-877-5p might become biomarkers to diagnose NSCL and dysregulation of these miRNAs might be involved in the progression of NSCL.


Assuntos
Biomarcadores/sangue , Fenda Labial/sangue , Fenda Labial/genética , Perfilação da Expressão Gênica , MicroRNAs/sangue , MicroRNAs/genética , Criança , Regulação para Baixo/genética , Ontologia Genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transdução de Sinais/genética , Regulação para Cima/genética
10.
J Craniofac Surg ; 27(2): e118-21, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26845090

RESUMO

OBJECTIVE: The aim of the study was to evaluate the changes in oxygen saturation and heart pulse during intraoral impression taking from infants with cleft lip and palate (CLP) at onset of presurgical orthopedic therapy. SUBJECTS AND METHODS: In our study, 21 uni- and bilateral infants with CLP (9 female, 12 males, mean age 5.90 ±â€Š2.46 days) were monitored and heart pulse and oxygen saturation were measured under operating conditions before any intervention (T1), after delivery of 50% supplemental oxygen (T2), during impression taking with oxygen support (T3), and immediately before the discharge from the operating room (T4). RESULTS: Statistically significant differences were found in the average oxygen saturation levels (P < 0.01), but not in heart rates (P > 0.05) between T1, T2, T3, and T4. Decreases in the oxygen levels from T2 to T3 were noted (P < 0.01). Overall, oxygen levels increased from T1 to T4 (P < 0.01). CONCLUSIONS: Oxygen saturation levels may decrease during intraoral impression taking in infants with CLP despite the supplemental oxygen under operating conditions. No changes in the heart rate during the procedure showed that the cardiac output was sufficient, whereas the decrease in oxygen saturation demonstrated hypoventilation because of the anatomic structure and impression-taking process. It may be advised that the impression should be taken under the supervision of the anesthetist, with monitoring of, and supplying oxygen to, the infant with CLP.


Assuntos
Fenda Labial/sangue , Fenda Labial/cirurgia , Fissura Palatina/sangue , Fissura Palatina/cirurgia , Técnica de Moldagem Odontológica , Oxigênio/sangue , Feminino , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Oxigenoterapia
11.
Artigo em Inglês | MEDLINE | ID: mdl-26503716

RESUMO

Cleft lip and cleft palate are among the most common birth defects worldwide. There is a genetic component to the development of these malformations, as well as evidence that environmental exposures and prescription drug use may exacerbate or even produce these manifestations. Thus, it is important to understand the underlying mechanisms and when these exposures affect development of the growing fetus. The purpose of this investigation was to critically review the available literature related to orofacial cleft formation following chemical exposure and identify specific time frames for windows of sensitivity. Further, an aim was to evaluate the potential for predicting effects in humans based on animal studies. Evidence indicates that chemical causes of cleft palate development are due to dose and timing of exposure, susceptibility of the species (i.e., the genetic makeup), and mechanism of action. Several studies demonstrated that dose is a crucial factor; however, some investigators argued that even more important than dose was timing of exposure. Data show that the window of sensitivity to environmental teratogens in the development of cleft palates is quite narrow and follows closely the window of palatogenesis in the fetus of any given species.


Assuntos
Fenda Labial/induzido quimicamente , Fenda Labial/embriologia , Fissura Palatina/induzido quimicamente , Fissura Palatina/embriologia , Exposição Ambiental , Teratogênicos/toxicidade , Animais , Fenda Labial/sangue , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Humanos
12.
Wei Sheng Yan Jiu ; 44(4): 543-8, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26454948

RESUMO

OBJECTIVE: To explore the relationship between polymorphism of interferon regulatory factor 6 (IRF6) gene rs642961 locus and nonsyndromic cleft lip with or without cleft palate (NSCL ± P). METHODS: There were 88 NSCL ± P nuclear families and 116 healthy people as control recruited from Chinese northern area. The polymorphism of IRF6 rs642961 locus was detected by tetra-primer amplification refractory mutation system-polymerase chain reaction (tetra-primer ARMS-PCR). Case-control analysis, transmission-disequilibrium test (TDT), haplotype-based haplotype relative risk analysis (HHRR) and family-based association test (FBAT) were carried out. RESULT: There was significant difference in rs642961 of IRF6 locus between the NSCL P group and control group, whether in children or parents (P < 0.05). The odds ratio (OR) of AG and AA versus GG is above one, and its 95% confidence interval did not include 1 in offspring, father and mother group, which meant genetic variant of rs642961 of IRF6 could increase the risk of occurrence of NSCL ± P. The allele transmission disequilibrium for rs642961 of IRF6 variant in NSCL ± P families was found by TDT analysis (P < 0.05). HHRR calculation also showed that there was association between the genetic variant and the occurrence of NSCL ± P (P < 0.05). While FBAT test showed that there was relationship between the genetic variant and the occurrence of NSCL ± P in addictive model. CONCLUSION: Polymorphism IRF6 gene locus is associated with NSCL ± P in northern Chinese population.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Fatores Reguladores de Interferon/genética , Polimorfismo Genético/genética , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Fenda Labial/sangue , Fissura Palatina/sangue , Primers do DNA , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Reação em Cadeia da Polimerase
13.
J Dent Res ; 93(6): 547-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24695672

RESUMO

Cleft of the lip and/or palate (CLP) is one of the most common congenital craniofacial defects. Non-syndromic CLP (NSCLP) is a multifactorial disease influenced by the interaction of genetic and environmental factors. However, there are few studies reporting on the developmental or metabolic status of babies with NSCLP after birth. In our study, we sought to identify and evaluate the differential expression of serum protein profiles in NSCLP children and unaffected babies. Thus, a 'shotgun proteomics' approach was first used to analyze the plasma proteome of 13 children with NSCLP and 10 control children, aged 2 to 3.5 years. In total, more than 300 proteins were identified in the serum sample. With gene ontology (GO) analysis, we detected many differentially expressed proteins that could be related to NSCLP, including those involved in lipoprotein metabolism, insulin-like growth-factor-related processes, and so on, especially the proteins involved in retinol transport. Retinol binding protein 4 (RBP4), one protein of the retinol transport category, was significantly decreased in the NSCLP group. Thus, serum vitamin A levels were further determined by high-performance liquid chromatography (HPLC). A significant difference (p < .01) was also found in vitamin A concentrations, consistent with the trend of RBP4. Our results indicated that reduced levels of RBP4 and vitamin A were related to newborns with NSCLP and should thus receive more attention. These results also suggest that vitamin A supplementation might be necessary at an early stage.


Assuntos
Fenda Labial/sangue , Fissura Palatina/sangue , Proteoma/análise , Proteínas Plasmáticas de Ligação ao Retinol/análise , Vitamina A/sangue , Proteínas Sanguíneas/análise , Western Blotting/métodos , Estudos de Casos e Controles , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Regulação da Expressão Gênica/genética , Ontologia Genética , Humanos , Lipoproteínas/metabolismo , Masculino , Somatomedinas/fisiologia , Vitamina A/metabolismo
14.
Turk J Med Sci ; 44(4): 696-702, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25551945

RESUMO

BACKGROUND/AIM: There are close interactions among the developing oral cavity, pituitary gland, and central nervous system (CNS) in early embryonic life. In this study we aimed to screen endocrine abnormalities in patients with orofacial clefts in the neonatal period. MATERIALS AND METHODS: Thirty-one patients with isolated orofacial median clefts wereincluded in the study. Pituitary, thyroid, and adrenal hormones were measured at the first week and remeasured in the third or fourth weeks. Imaging studies were done for detection of CNS anomalies in all patients. RESULTS: Endocrine abnormality was detected in 22 (70.9%) patients. The number of patients with single and multiple endocrine abnormalities were 13 (41.9%) and 9 (29%), respectively. Thyroid hormone-related disorders were detected in 10 (32.3%) patients. Growth hormone deficiency was detected in 4 (12.9%) patients. Adrenocorticotrophic hormone and/or glucocorticoid deficiency was detected in 5 (16.1%) patients. Neonatal hypoglycemia due to endocrinological abnormalities was detected in 6 (19.4%) patients. Defected mini-puberty was seen in 2 (15.4%) patients. There was no relationship between the types of orofacial cleft and endocrine abnormalities. CONCLUSION: Endocrinological evaluation of the patients with orofacial clefts in the neonatal period is a worthwhile endeavor to detect hormone deficiencies regardless of the type of the cleft.


Assuntos
Anormalidades Múltiplas/sangue , Corticosteroides/sangue , Fenda Labial/sangue , Fissura Palatina/sangue , Hormônios Hipofisários/sangue , Hormônios Tireóideos/sangue , Fenda Labial/complicações , Fissura Palatina/complicações , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Masculino , Malformações do Sistema Nervoso/sangue , Malformações do Sistema Nervoso/complicações
15.
J Craniofac Surg ; 25(1): 103-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24275774

RESUMO

INTRODUCTION: Birth abnormalities like cleft lip and cleft palate account for about 1.4 per 1000 live births in India. These are seen to be associated with a high incidence of eosinophilia which delays the surgical management of these patients. AIMS: The aim of this paper is to study the hematological parameters in patients of cleft lip and cleft palate. PATIENTS AND METHODS: A total of 223 cases of cleft lip and cleft palate were taken up for the study. Hematological parameters including hemoglobin, total leukocyte count, differential leukocyte count, absolute eosinophil count, and red cell indices were studied. RESULTS: Anemia was found in 182/223 (81.63%) cases which was most commonly of microcytic hypochromic type. Eosinophilia was seen in 46/223 (20.60%) cases. CONCLUSIONS: Many cleft lip and cleft palate patients show high eosinophil counts. Absolute eosinophil count was found to be a better parameter for assessment of eosinophils.


Assuntos
Fenda Labial/sangue , Fissura Palatina/sangue , Eosinófilos/patologia , Adulto , Anemia/sangue , Anemia Hipocrômica/sangue , Criança , Pré-Escolar , Eosinofilia/sangue , Índices de Eritrócitos , Feminino , Hemoglobinas/análise , Humanos , Lactente , Contagem de Leucócitos , Leucocitose/sangue , Leucopenia/sangue , Masculino , Estudos Prospectivos
16.
J Oral Maxillofac Surg ; 71(9): 1601.e1-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23642547

RESUMO

PURPOSE: The pathogenesis and prevention of cleft lip and palate (CL/P) have been studied mainly in clinical and animal experiments. A prophylactic poly-B-vitamin substitution during the first months of pregnancy has provided the most encouraging results for the prevention of CL/P recurrence in families at risk. In vitro studies of the palatal organ in an A/WySn mouse model have confirmed the positive influence of B-vitamins on palatal development. The present animal study was performed to analyze different B-vitamin concentrations in the serum and amniotic fluid of A/WySn mice according to the appearance of CL/P in their offspring. MATERIAL AND METHODS: Concentrations of different B-vitamins (B1, B2, B3, B5, B6, and folic acid) in serum and amniotic fluid were analyzed by high-performance liquid chromatographic detection. Immunohistochemical staining against thiamin-1 receptor was performed on histologic midface sections of A/WySn fetuses with (n = 12) and without (n = 14) CL/P. RESULTS: Vitamin B5 (P < .001) and folic acid (P < .004) concentrations in the amniotic fluid of dams with CL/P were significantly lower than in dams without CL/P. Serum concentrations of folic acid (P = .5) and B5 (P = .4) showed no difference between the 2 groups. Dams with CL/P had significantly lower thiamine concentrations in serum (P = .01) and amniotic fluid (P < .001). Histologic midface sections presented high thiamin-1 receptor expression in the palatal shelf of fetuses with CL/P. CONCLUSION: A decreased use or uptake of some B-vitamin subgroups (B1, B5, and folic acid) in amniotic fluid and serum (vitamin B1) was correlated to an increased cleft appearance in A/WySn mice. The high thiamin-1 receptor expression in the palatal tissue of mouse fetuses with CL/P may be caused by a decreased availability of vitamin B1.


Assuntos
Líquido Amniótico/química , Fenda Labial/embriologia , Fissura Palatina/embriologia , Complexo Vitamínico B/sangue , Adenina/análise , Adenina/sangue , Fosfatase Alcalina/análise , Animais , Cromatografia Líquida de Alta Pressão , Fenda Labial/sangue , Fenda Labial/metabolismo , Fissura Palatina/sangue , Fissura Palatina/metabolismo , Modelos Animais de Doenças , Feminino , Ácido Fólico/análise , Ácido Fólico/sangue , Imuno-Histoquímica , Indicadores e Reagentes , Proteínas de Membrana Transportadoras/análise , Proteínas de Membrana Transportadoras/sangue , Camundongos , Camundongos Endogâmicos , Niacinamida/análise , Niacinamida/sangue , Nitroazul de Tetrazólio , Palato/patologia , Ácido Pantotênico/análise , Ácido Pantotênico/sangue , Gravidez , Riboflavina/análise , Riboflavina/sangue , Tiamina/análise , Tiamina/sangue , Vitamina B 6/análise , Vitamina B 6/sangue , Complexo Vitamínico B/análise
17.
J Biosci ; 38(1): 21-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23385809

RESUMO

In India, as in other parts of the world, nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) is a highly prevalent birth defect, its incidence in males being twice that in females. A case-control association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and SLC19A1 (RFC1) G80A genotypes from an eastern Indian cohort to investigate whether Hcy and other Hcy-pathway genes also contribute to the risk level. While MTHFR 677T and SLC19A1 80G are individually and cumulatively risk factors, SLC19A1 80A appears to be protective against MTHFR 677T risk allele. Elevated Hcy associates with NSCL +/- P both in case mothers and cases. Significantly, this difference shows a gender bias: the level of elevation of Hcy in female cases is distinctly higher than in males, and more case females are hyperhomocyteinemic than the case males. It implies that compared with the males, higher level of Hcy is needed for NSCL +/- P to manifest in the females. We consider this as one of the possible factors why the incidence of this disorder in females is much lower than in males.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Proteína Carregadora de Folato Reduzido/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Fenda Labial/sangue , Fenda Labial/epidemiologia , Fissura Palatina/sangue , Fissura Palatina/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Incidência , Índia/epidemiologia , Lactente , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/sangue , Proteína Carregadora de Folato Reduzido/sangue , Fatores de Risco , Fatores Sexuais
18.
Arch Oral Biol ; 58(5): 459-61, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23395542

RESUMO

BACKGROUND/PURPOSE: In mice, biotin deficiency is one of the most potent clefting factors. Increased 3-hydroxyisovalerylcarnitine (C5OH) is regarded as a biomarker of biotin deficiency. This retrospective study was undertaken to determine whether increased C5OH in newborns is associated with orofacial clefts. MATERIALS AND METHODS: Seventy newborns with non-syndromic cleft lip with or without cleft palate and 140 control newborns without congenital anomalies were investigated. Whole-blood C5OH concentrations were measured using tandem mass spectrometry. RESULTS: The median (interquartile range, IQR) concentrations of C5OH in patients with clefts and controls were 0.16 (0.13-0.22)µmoll(-1) and 0.17 (0.13-0.20)µmoll(-1), respectively (p=0.90). The receiver operating characteristic analysis did not find out cut-off values for C5OH discriminating between cases and controls. CONCLUSION: There appears to be no association between biotin deficiency, as indexed by an increase of C5OH, and orofacial clefts in the investigated group of patients.


Assuntos
Biotina/deficiência , Carnitina/análogos & derivados , Fenda Labial/etiologia , Fissura Palatina/etiologia , Deficiência de Vitaminas do Complexo B/complicações , Carnitina/sangue , Fenda Labial/sangue , Fissura Palatina/sangue , Humanos , Recém-Nascido , Polônia/etnologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Espectrometria de Massas em Tandem , Deficiência de Vitaminas do Complexo B/sangue , População Branca
19.
Plast Reconstr Surg ; 130(5): 1120-1130, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23096613

RESUMO

BACKGROUND: Cleft lip repair aims to normalize the disturbed anatomy and function. The authors determined whether normalization of blood circulation is achieved. METHODS: The authors measured the microcirculatory flow, oxygen saturation, and hemoglobin level in the lip and nose of controls (n = 22) and in patients with unilateral and bilateral cleft lip-cleft palate. The authors measured these parameters before lip repair (n = 29 and n = 11, respectively), at the end of lip repair (n = 27 and 10, respectively), and in the late postoperative period (n = 33 and n = 20, respectively). The arterial flow velocity was measured in unilateral groups at the same time points (n = 13, n = 11, and n = 12, respectively). Statistical differences were determined using analysis of variance. RESULTS: Before surgery, the arterial flow velocities and microcirculation values were similar on each side of the face and between groups. The microcirculatory flow was significantly higher in the prolabium of bilateral patients than in the philtrum of controls. All circulation values in unilateral and bilateral patients in the late postoperative period were within the range of controls and of those before surgery. Intraoperatively, the authors consistently found a perforating artery on the superficial side of the transverse nasalis muscle. CONCLUSIONS: There appears to be no intrinsic circulatory deficit in unilateral and bilateral cleft lip-cleft palate patients. The increased flow in the prolabium indicates a strong hemodynamic need in this territory, compelling its vascular preservation. Whether surgical preservation of the nasalis perforator artery is of long-term benefit should be addressed in future studies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.


Assuntos
Fenda Labial/fisiopatologia , Fenda Labial/cirurgia , Lábio/irrigação sanguínea , Lábio/fisiologia , Nariz/irrigação sanguínea , Nariz/fisiologia , Velocidade do Fluxo Sanguíneo , Fenda Labial/sangue , Fissura Palatina/sangue , Fissura Palatina/fisiopatologia , Hemoglobinas/análise , Humanos , Período Intraoperatório , Microcirculação/fisiologia
20.
Eur J Clin Invest ; 42(7): 738-50, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22896855

RESUMO

BACKGROUND: Maternal periconceptional use of folic acid contributes to the prevention of neural crest-related congenital malformations including orofacial clefts. The underlying biological pathways affected by folic acid,however, are still not clarified. In an explorative study, we identify folate-responsive proteins and pathways by advanced proteomic techniques and their possible role in orofacial development in young children. MATERIALS AND METHODS: At 15 months of age, we obtained B lymphoblasts from 10 children with and 10 children without an orofacial cleft. Folate-responsive protein expression was determined in folate-free B-lymphoblast cultures, supplemented with 5-methyltetrahydrofolate to reach the target concentration 30 nM. Folate-associated differences of peptide and protein expressions were assessed by analysing samples before and after folate addition. Samples were trypsin digested and measured by nano-liquid chromatography coupled online to a LTQ-Orbitrap mass spectrometer. Significantly differentiating peptides were determined using a McNemar's test, and correlations with proteins and existing pathways were visualized using Ingenuity Pathway Analysis. RESULTS: We found 39 folate-responsive peptides that were assigned to 30 proteins. Those proteins consisted of histones, ribosomal and heat shock proteins (HSP), and proteins involved in antioxidant reactions, cytoskeleton,glycolysis, energy production, protein processing, signal transduction and translation. CONCLUSIONS: Histones, ribosomal and HSP were mainly found in the case group, and we confirm that almost 60% of these proteins were also found in a subset of the samples in our previous study using microarray on folate-responsive gene expression. The proteins were compared with known biological pathways and matched with recent relevant literature.


Assuntos
Linfócitos B/efeitos dos fármacos , Fenda Labial/sangue , Fissura Palatina/sangue , Fragmentos de Peptídeos/metabolismo , Mapeamento de Peptídeos/métodos , Tetra-Hidrofolatos/farmacologia , Linfócitos B/metabolismo , Encéfalo/anormalidades , Estudos de Casos e Controles , Células Cultivadas , Feminino , Proteínas de Choque Térmico/metabolismo , Histonas/metabolismo , Humanos , Lactente , Masculino , Espectrometria de Massas , Gravidez , Proteínas Ribossômicas/metabolismo
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