Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
ACS Appl Mater Interfaces ; 15(40): 47260-47277, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37751537

RESUMO

Variants of garnet-type Li7La3Zr2O12 are being intensively studied as separator materials in solid-state battery research. The material-specific transport properties, such as bulk and grain boundary conductivity, are of prime interest and are mostly investigated by impedance spectroscopy. Data evaluation is usually based on the one-dimensional (1D) brick layer model, which assumes a homogeneous microstructure of identical grains. Real samples show microstructural inhomogeneities in grain size and porosity due to the complex behavior of grain growth in garnets that is very sensitive to the sintering protocol. However, the true microstructure is often omitted in impedance data analysis, hindering the interlaboratory reproducibility and comparability of results reported in the literature. Here, we use a combinatorial approach of structural analysis and three-dimensional (3D) transport modeling to explore the effects of microstructure on the derived material-specific properties of garnet-type ceramics. For this purpose, Al-doped Li7La3Zr2O12 pellets with different microstructures are fabricated and electrochemically characterized. A machine learning-assisted image segmentation approach is used for statistical analysis and quantification of the microstructural changes during sintering. A detailed analysis of transport through statistically modeled twin microstructures demonstrates that the transport parameters derived from a 1D brick layer model approach show uncertainties up to 150%, only due to variations in grain size. These uncertainties can be even larger in the presence of porosity. This study helps to better understand the role of the microstructure of polycrystalline electroceramics and its influence on experimental results.

2.
J Craniomaxillofac Surg ; 50(3): 254-261, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34930667

RESUMO

The aim of this study is to describe the growth of the upper lip after reconstruction with a Pfeifer wave-line incision in patients with unilateral and bilateral cleft lip and palate (CL/P) in the long term. This was a longitudinal, monocentric, retrospective study. Metric standardized lip length measurements were taken annually from the age of 6 months to the age of 16 years. Defined anatomical points were determined which describe the lip length from the nasal entrance to the highest point of the Cupid's bow. The lip length of the unaffected side in unilateral cleft patients was taken as control. A total of 234 patients with cleft lip with/without cleft palate (CL/P) were included in the study. At the time of the primary surgery, the medial sides in unilateral clefts were 2-4 mm and the lateral sides 1.5-2 mm shorter than the normal unaffected side (p≤0.001). Two main periods of growth, one during childhood (first to sixth years) and one during adolescence (12th-16th years) were seen. At the age of 16 years, the end of the observation period, the lip length in unilateral clefts resulted in a clinically not noticeable shortening of the cleft side (0.37±0.26 mm). There was no correlation between lip length development and primary cleft width at the time of primary cleft lip surgery at 6 months. The upper lip in patients with bilateral clefts developed symmetrically without any obvious asymmetry. Both sides showed a lip length difference of 0.1±0.05 mm at the age of 16 years (p=0.1). Compared to the upper lip length of the control group, bilateral clefts showed a slight tendency toward a longer upper lip (p=0.52). Within the limitations of the study it seems that when lip length development is a priority in cleft lip surgery, Pfeifer wave-line procedure is good option to achieve symmetric results in unilateral and bilateral cleft lip surgery and, therefore, is a relevant option among a variety of other techniques.


Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Humanos , Lactente , Lábio/cirurgia , Nariz , Estudos Retrospectivos
3.
Int J Mol Sci ; 20(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554283

RESUMO

The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells.


Assuntos
Metabolismo Energético , Glutamina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/metabolismo , Acetilação , Ácido Ascórbico/metabolismo , Anidrase Carbônica IX/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glicólise , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias/genética , Neoplasias/patologia , Estabilidade Proteica , RNA Interferente Pequeno/genética
4.
J Craniomaxillofac Surg ; 45(12): 1948-1954, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29037922

RESUMO

PURPOSE: Cleft lip and palate (CL/P) are one of the most common human birth defects. Animal experiments and clinical investigations show a clear reduction of teratogenic clefts by a high-dose vitamin B supplementation during early pregnancy, especially in families at risk (reduction of recurrence). The aim of this work was to examine the influence of thiamine (vitamin B1) on CL/P appearance in genetically determined A/WySn mice within different supplementation starting points. MATERIALS AND METHODS: A total of 24 A/WySn female mice were orally supplemented with high doses (80 mg/kg) of thiamine at different times of pregnancy (5 groups, n = 90). The influence of thiamine on the abortion rate and CL/P appearance in the offspring was analyzed with respect to the concentration of thiamine in the serum and amniotic fluid (HPLC-chromatography). Immunochemical analyses of the ThTr-1 und ThTr-2 receptor-status were performed in midface sections of A/WySn-fetuses and the corresponding placenta, with and without CL/P. RESULTS: High doses of orally supplemented thiamine did not reduce the CL/P appearance in A/WySn mice. However, the different starting points of vitamin B1 substitution had some influence. Additionally, an obvious decrease in aborted fetuses was noticed in all supplemented groups. The oral substitution caused a clear increase of the serum concentration in all mothers, but showed no increase of the amniotic fluid concentration. Then immunohistochemistry detected an overexpression of ThTr-1 in the midface and an irregular localization of ThTr-2 in the placenta of fetuses with clefts. CONCLUSION: Our results suggest a time-dependent influence of thiamine on CL/P appearance in female mice. The prophylactic/periconceptional, but not the therapeutic supplementation, starting point can be proposed as a crucial step for regular facial and palatal fusion in embryonic development. The absolute rate of CL/P was not reduced, and the concentration of the water-soluble thiamine could not increase in the amniotic fluid. Thus the proposed local effect of thiamine failed in the development of genetically determined mice.


Assuntos
Fenda Labial/genética , Fenda Labial/prevenção & controle , Fissura Palatina/genética , Fissura Palatina/prevenção & controle , Suplementos Nutricionais , Tiamina/administração & dosagem , Administração Oral , Animais , Fenda Labial/embriologia , Fissura Palatina/embriologia , Feminino , Camundongos , Gravidez , Falha de Tratamento
5.
Clin Oral Investig ; 21(1): 211-224, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26955835

RESUMO

OBJECTIVES: The stabilization of the transcription factor and prognostic tumor marker hypoxia-inducible factor 1α (HIF1α) is considered to be crucial for cellular metabolic adaptations to hypoxia. However, HIF1α has also been shown to accumulate under normoxic conditions, although this phenomenon is poorly understood. METHODS: We investigated the conditions for normoxic HIF1α stabilization in different tumor cell lines (e.g., two mammary carcinoma cell lines and three oral squamous cell carcinoma cell lines) via Western blot analysis or immunohistochemical staining. The transcriptional activity of HIF1 was demonstrated by analyzing the messenger RNA (mRNA) expression of the HIF1 target carbonic anhydrase 9 (CA9) via PCR. RESULTS: Our data demonstrate that the combined incubation of tumor cells with glutamine and growth factors (e.g., EGF, insulin, and serum) mediates the normoxic accumulation of HIF1α in vitro. Consequently, the inhibition of glutaminolysis by a glutaminase inhibitor blocked the normoxic accumulation of HIF1α. Additionally, the normoxic HIF1α protein displayed nuclear translocation and transcriptional activity, which was confirmed by the induction of CA9 mRNA expression. Furthermore, the normoxic accumulation of HIF1α was associated with impaired proliferation of tumor cells. Finally, ammonia, the toxic waste product of glutaminolysis, induced a normoxic accumulation of HIF1α to the same extent as glutamine. CONCLUSION: Our study suggests that HIF1α is involved in the regulation of glutamine metabolism and the cellular levels of the toxic metabolic waste product ammonia under normoxia. Hence, our results, together with data presented in the literature, support the hypothesis that HIF1α and its target genes play a crucial role in metabolic pathways, such as glutaminolysis and glycolysis, under both hypoxic and normoxic conditions. CLINICAL RELEVANCE: Therefore, the inhibition of HIF1α (and/or HIF1α target genes) could emerge as a promising therapeutic approach that would result in the accumulation of toxic metabolic waste products in tumor cells as well as the reduction of their nutrition and energy supply.


Assuntos
Anidrase Carbônica IX/metabolismo , Glutamina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Amônia/metabolismo , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Reação em Cadeia da Polimerase , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo
6.
J Craniomaxillofac Surg ; 44(2): 104-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26712483

RESUMO

PURPOSE: Cleft lip and/or palate (CL/P) shows a gender-related distribution in human beings. The reason is unknown. This study analyzed the gender-related cleft appearance with respect to teratogenically and genetically determined cleft appearance and the response to thiamine (vitamin B1) supplementation. MATERIAL AND METHODS: Cyclophosphamide (CPA; 0.6 mg) and dexamethasone (0.25 mg) were injected intraperitoneally to A/B-Jena mice on different days of pregnancy. The abortion and malformation rate in the A/B-Jena and A/WySn mice with genetically determined clefting was documented to be gender-specific. Vitamin B1 was given to A/B-Jena dams at different times during pregnancy before, simultaneously and after the teratogenic agent was given to the pregnant mothers. A/WySn mice received oral supplementation at different times during embryonic/fetal development. RESULTS: There were significantly more living female fetuses when mothers were treated with teratogens, and the embryo lethality and malformation affected more male individuals. However, the survival and malformation rate in A/WySn mice was not gender-specific. Especially in male fetuses, vitamin B1 decreased the teratogenic cleft rate (CPA: p < 0.001, dexamethasone: p = 0.6), whereas there was no effect in the A/WySn mice. CONCLUSION: There was a strong anti-teratogenic effect of vitamin B1, especially in the male fetuses. Genetically determined cleft appearance was not positively influenced. These findings confirm observations about cleft appearance in human beings.


Assuntos
Fissura Palatina/genética , Tiamina/farmacologia , Vitaminas/farmacologia , Animais , Fenda Labial , Fissura Palatina/prevenção & controle , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Gravidez , Distribuição por Sexo , Teratogênicos
7.
J Craniomaxillofac Surg ; 43(9): 1809-22, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26321065

RESUMO

Over a century after the first synthesis of bisphosphonates (1897) and a decade (2003) since the initial report on bisphosphonate-related osteonecrosis of the jaw (ONJ), this osteopathy remains a serious clinical challenge. A single center longitudinal study (2005-2014) was carried out to prospectively characterize inpatients with manifest ONJ and to evaluate their outcomes. The data recorded were: medical history, bisphosphonate treatment, localization, imaging, treatment, histomorphological features, and complications. A prognostic score (modified UCONN-Score) was adopted to predict outcomes. Eighty patients were included (mean age 69.4 years; 40 male, 40 female). Breast cancer (n = 25), multiple myeloma (n = 16), and prostate cancer (n = 15) were the three most common malignancies; and cardiovascular disease (n = 31), diabetes mellitus (16), and renal disorders (6) were the most important comorbidities. The severity of ONJ was stage I in three patients, stage II in 37, and stage III in 40, being predominantly localized in the posterior mandible and needing gradual resection. The average duration of bisphosphonate treatment was 38.3 months. The typical histological aspects of ONJ were predominantly osteonecrosis, bone marrow fibrosis, and bacterial colonization (Actinomyces) with suppurative inflammation. Within the resected jawbone a primary malignancy was diagnosed in two cases. The overall success rate was 83.6% (follow-up 23.5 months), with a UCONN-Score ≥15 predicting unfavorable treatment results (OR = 5.2). The past decade has enhanced experience with ONJ treatment and knowledge about its pathogenesis, which seems to be a multistep process. This study demonstrates the importance of bone and multilayer soft tissue management, preferably as an early intervention. The UCONN-Score might help to assess individual prognosis in ONJ surgery and the potential benefit of an antiresorptive drug holiday. To our knowledge it is the first use of a prognostic score in ONJ surgery.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Comorbidade , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Estudos Longitudinais , Masculino , Microcirurgia , Prognóstico , Radiografia Panorâmica , Medição de Risco , Tomografia Computadorizada de Emissão de Fóton Único
8.
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
9.
J Oral Maxillofac Surg ; 71(1): 143-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22695017

RESUMO

PURPOSE: This study analyzed the direct influence of vitamin B-complex supplements (Polybion N, Merck Pharma GmbH, Germany) in medium on secondary palatal development in palatal organ cultures of A/WySnJ mice. Because of positive clinical experiences with prophylactic vitamin B substitution in mothers of cleft-related families, the direct influence of the vitamin B-complex on palatal tissue was analyzed. MATERIALS AND METHODS: The inbred A/WySnJ mouse strain shows a highly spontaneous, genetically determined clefting rate of 20% to 44%. One hundred seventy-seven A/WySnJ fetuses were microdissected on gestational day 14.3 before the occurrence of palatal fusion. Palatal organ cultures were prepared and incubated in chemically defined serum-free medium with different concentrations (0.1% and 1.0%) of the vitamin B-complex Polybion N for 72 hours. Palatal development was analyzed microscopically according to the 6-step visual scale that describes the approximation of palatal shelves during development. RESULTS: At the beginning of the experiment (gestational day 14.3), the palatal development of all specimens used for in vitro organ culture showed a clear approach of the palatal shelves at stage II (2.25±0.78). Seventy-two hours after in vitro cultivation, the palatal shelves of the organ cultures supplemented with the vitamin B-complex showed significant growth (0.1%, P=.00017; 1.0%, P=.00078), whereas the untreated control group remained at initial developmental stage II (P=.291). CONCLUSIONS: The results of this in vitro study suggest a significant positive influence of vitamin B supplementation on palatal shelf development in organ culture. Further studies will focus on the vitamin B concentration in the amniotic fluid of dams with or without cleft in their offspring.


Assuntos
Palato Duro/efeitos dos fármacos , Palato Duro/embriologia , Complexo Vitamínico B/farmacologia , Animais , Fissura Palatina/genética , Fissura Palatina/prevenção & controle , Camundongos , Camundongos Endogâmicos , Modelos Organizacionais
10.
Cell Cycle ; 11(21): 3932-6, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22987151

RESUMO

It is well known that the hypoxia-inducible factor 1 α (HIF1α) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1α is detectable even under normoxic conditions, if the metabolism is altered, e.g., high proliferation index. Importantly, both hypoxic metabolism and the Warburg effect have in common a decrease of the intracellular pH value. In our interpretation, HIF1α is not directly accumulated by hypoxia, but by a process which occurs always under hypoxic conditions, a decrease of the intracellular pH value because of metabolic imbalances. We assume that HIF1α is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1α has its major role in activating genes to eliminate toxic metabolic waste products (e.g., NH3/NH4+) generated by the tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or the Warburg effect. For that reason, HIF1α appears as a potential target for tumor therapy to disturb the pH balance and to inhibit the elimination of toxic metabolic waste products in the tumor cells.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/metabolismo , Amônia/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/patologia , Compostos de Amônio Quaternário/metabolismo
11.
Wien Med Wochenschr ; 162(13-14): 316-20, 2012 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-22669314

RESUMO

The microflora of odontogenic infections is typically polymicrobial with increased resistance rates against various antibiotics. The purpose of the present study was to analyze bacterial spectra and resistance in odontogenic infections under routineous conditions.Microbiological samples were collected and transported under routineous conditions in a prospective study of 19 patients. All Bacterial spectra and resistance rates were compared with the results of a former prospective evaluation.There were 11 men, 5 woman and 3 children (age range of 2-86 years). A total of only 38 bacterial strains were analyzed. The ratio between aerobes and anaerobes was nearly 1:1. The resistance rates were nearly the same for Penicillin G, but a 2-fold increased resistance for clindamycin against aerobes and a more than 10-fold increased resistance against anaerobes was noted.Prospective studies under standardized conditions are necessary to isolate strict anaerobes and to detect changes in antibiotic efficiency.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Anaeróbias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana Múltipla , Abscesso Periapical/tratamento farmacológico , Abscesso Periapical/microbiologia , Abscesso Periodontal/tratamento farmacológico , Abscesso Periodontal/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resistência às Penicilinas , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
12.
BMC Cancer ; 11: 429, 2011 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-21978106

RESUMO

BACKGROUND: The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet. METHODS: Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type LGR5/GPR49 and a newly identified splice variant of LGR5/GPR49 lacking exon 5 (that we called GPR49Δ5) were quantified. RESULTS: A low mRNA expression level of GPR49Δ5, but not wild type LGR5/GPR49, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of GPR49Δ5 was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of GPR49Δ5 mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of GPR49Δ5 mRNA. CONCLUSION: An attenuated mRNA level of the newly identified transcript variant GPR49Δ5 is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower GPR49Δ5 mRNA level is associated with a later age of tumor onset. A putative role of GPR49Δ5 expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested.


Assuntos
Processamento Alternativo , Receptores Acoplados a Proteínas G/genética , Sarcoma/genética , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adulto Jovem
13.
Histopathology ; 58(7): 1136-47, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21438910

RESUMO

AIMS: To study whether coexpression of the two hypoxia-related proteins hypoxia-inducible factor (HIF)-1α and glucose transporter (GLUT)-1 has prognostic relevance in oral squamous cell carcinomas (OSCCs). METHODS AND RESULTS: Eighty-two OSCC samples were analysed for expression levels of HIF-1α and GLUT-1 by immunohistochemistry. Protein expression was assessed with an immunoreactive score system, and the correlations between gene expression and both clinical and pathohistological parameters were examined. Overexpression of either GLUT-1 or HIF-1α was associated with poor disease-specific survival in OSCC patients. Multivariate Cox proportional-hazards regression analysis revealed that increased expression of HIF-1α was significantly associated with disease-specific survival (relative risk = 3.24, P = 0.024), as compared with the group with a low level of expression. Coexpression of HIF-1α and GLUT-1 was additively and significantly associated with adverse prognoses in patients with OSCC. Patients whose tumours had increased levels of expression of both HIF-1α and GLUT-1 were found to have a 5.13-fold increased risk of tumour-related death (P = 0.017). CONCLUSIONS: Coexpression of high levels of HIF-1α and GLUT-1 is significantly correlated with prognosis in OSCC patients, suggesting that the coexpression of these proteins can be used as both an early diagnostic and independent prognostic marker.


Assuntos
Carcinoma de Células Escamosas/secundário , Transportador de Glucose Tipo 1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Feminino , Alemanha/epidemiologia , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Adulto Jovem
15.
Int J Biol Markers ; 25(2): 87-92, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20544685

RESUMO

The critical molecular regulator of hypoxia is the hypoxia-inducible factor 1 alpha (HIF-1alpha). The prognostic impact of this regulator protein in oral squamous cell carcinomas (OSCC) has not been comprehensively investigated. The aim of this study was to analyze the expression of HIF-1alpha in 82 patients with OSCC and to correlate it with their disease-specific survival. Immunohistochemical staining for HIF-1alpha was performed on 82 OSCC specimens using a standard immunoperoxidase technique. The expression of HIF-1alpha was correlated with poor disease-specific survival for OSCC patients. Patients with negatively or weakly HIF-1alpha-expressing tumors had a survival rate of 80%, whereas the survival decreased to only 33.6% in case of moderate or strong expression. In multivariate Cox regression analysis, we found a 3.5-fold increased risk of tumor-related death when HIF-1alpha was strongly expressed (p=0.016) compared to negative or weak expression of HIF-1alpha. We suggest HIF-1alpha is an independent prognostic marker in OSCC. Immunohistochemical detection of HIF-1alpha appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Neoplasias Bucais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
16.
J Craniomaxillofac Surg ; 38(8): 601-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20223677

RESUMO

A case of cervical lymph node infiltration by a benign cellular blue nevus (CBN) and a 27-year disease history is presented. Dermal dendritic melanocytes and pigmented spindle cells presented no histological evidence of malignancy (CD34-, desmin-, PanCy-, HMB-45+, anti-S-100+, Bcl-2+, MART-1+, focally expression of melan A, 1% Ki-67+ of the tumour cell nucleoli). The differentiation of the benign blue nevus (BN) from a malignant blue nevus (MBN) and a malignant melanoma (MM) is still a challenge. Because of the malignant transformation potential of 5.2-6.3% a histological examination and a conservative surgical approach with close follow up are mandatory.


Assuntos
Linfonodos/patologia , Nevo Azul/patologia , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Pescoço , Nevo Azul/cirurgia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento
17.
Br J Oral Maxillofac Surg ; 48(2): 100-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19647911

RESUMO

Surgical treatment of cancers of the oral cavity often requires resection of the mandible, which sacrifices continuity, thereby implying considerable loss of function and aesthetics. The aim of the present study was to compare different methods of mandibular reconstruction for long-term results, complications, and factors associated with failure. During the 10-year period (1995-2005), 102 patients (73 men and 29 women, mean age 55 years, range 11-83) had a continuity resection of the mandible as described by Jewer et al. as follows: lateral continuity defect (n=53), central/lateral continuity defect (n=24), lateral/central/lateral continuity defect (n=14), central continuity defect (n=6), hemimandibular continuity defect (n=4) and central/hemimandibular continuity defect (n=1). The gap in the mandible was bridged with a titanium reconstruction plate in 73 patients, four of whom required a temporomandibular joint prosthesis. In 29 patients the mandibles were reconstructed with free autologous bone grafts fixed with miniplates. The overall 1-year success rate was 64%; 66% for the 73 patients who had miniplate/bone fixation and 63% in the 29 whose defects were bridged with a reconstruction plate. Complications were associated with the reconstruction plate in 39%. The most common complications were extraoral exposure (16%), intraoral exposure (10%), loose osteosynthesis screws (5%), fractures of the reconstruction plate (5%), and extra/intraoral exposure (1%). All fractures were noted at least 6 months postoperatively. There was no increased risk (p=0.67) depending on the osteosynthesis device used (miniplate or reconstruction plate). The risk of failure of the reconstruction plate was significantly higher in men (p=0.002) and smokers (p=0.004), whereas no increased risk was apparent for the anatomical site of the defect. Radiation reduced the 1-year success rate from 64% to 45% but not significantly so (p=0.67). There were no significant differences between the reconstruction methods. Alloplastic reconstruction devices are the treatment of choice for many patients.


Assuntos
Mandíbula/cirurgia , Neoplasias Mandibulares/reabilitação , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Placas Ósseas , Transplante Ósseo , Carcinoma de Células Escamosas/reabilitação , Carcinoma de Células Escamosas/cirurgia , Criança , Irradiação Craniana , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Neoplasias Mandibulares/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de Risco , Fumar , Falha de Tratamento , Adulto Jovem
18.
Oral Maxillofac Surg ; 13(2): 73-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19319581

RESUMO

UNLABELLED: PURPOSE AND RESULTS: The aim of this prospective study was to determine the incidence of postoperative bleeding after oral surgery under local anaesthesia performed in outpatients with haemostatic disorders within a 5-year period (2003-2007). One hundred twenty one (70 males, 51 females) out of 2,056 outpatients with different haemostatic disorders (acquired or hereditary) were included in this study. The following data were recorded: medical history and general condition; medications; indication for the surgical procedure; specification of local anaesthesia; applied surgical techniques, considering the kind of haemostatic disorder; and peri- or postoperative bleeding complications. Postoperative bleeding was observed in 12 patients (9.9%). In three cases, inpatient treatment became necessary. The management of two patients with a haemostatic disorder (von Willebrand s disease and haemophilia A) is presented in short case reports. CONCLUSION: In a heterogeneous group of 121 outpatients with known haemostatic disorders, a combination of a few haemostatic agents with appropriate operative technique enables an effective wound management. In cases of failed local interventions after postoperative bleeding, further diagnostic investigations are required.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Transtornos da Coagulação Sanguínea/epidemiologia , Hemorragia Bucal/epidemiologia , Procedimentos Cirúrgicos Bucais/estatística & dados numéricos , Hemorragia Pós-Operatória/epidemiologia , Aumento do Rebordo Alveolar , Anestesia Local , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Adesivo Tecidual de Fibrina/uso terapêutico , Alemanha/epidemiologia , Hemofilia A/complicações , Hemostasia Cirúrgica/estatística & dados numéricos , Hemostáticos/uso terapêutico , Humanos , Incidência , Masculino , Anamnese , Pessoa de Meia-Idade , Hemorragia Bucal/terapia , Hemorragia Pós-Operatória/terapia , Estudos Prospectivos , Extração Dentária , Adulto Jovem , Doenças de von Willebrand/complicações
19.
J Oral Maxillofac Surg ; 66(12): 2537-44, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19022134

RESUMO

PURPOSE: This randomized, clinical multicenter trial investigated the treatment outcomes of displaced condylar fractures, and whether radiographic fracture level was a prognostic factor in therapeutic decision-making between open reduction and internal fixation (ORIF) versus closed reduction and mandibulomaxillary fixation (CRMMF). PATIENTS AND METHODS: Sixty-six patients with 79 displaced fractures (deviation of 10 degrees to 45 degrees, or shortening of the ascending ramus >or=2 mm) of the condylar process of the mandible at 7 clinical centers were enrolled. Patients were randomly allocated to CRMMF (n = 30 patients) or ORIF (n = 36 patients) treatment. The following parameters were measured 6 months after the trauma. Clinical parameters included mouth opening, protrusion, and laterotrusion. Radiographic parameters included level of the fracture, deviation of the fragment, and shortening of the ascending ramus. Subjective parameters included pain (according to a visual analogue scale), discomfort, and subjective functional impairment with a mandibular functional impairment questionnaire. RESULTS: The difference in average mouth opening was 12 mm (P or=2 mm, should be treated with ORIF, irrespective of level of the fracture.


Assuntos
Fixação de Fratura/instrumentação , Fixação de Fratura/métodos , Técnicas de Fixação da Arcada Osseodentária/instrumentação , Côndilo Mandibular/lesões , Fraturas Mandibulares/cirurgia , Tomada de Decisões , Fixação Interna de Fraturas/instrumentação , Humanos , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/patologia , Dor Pós-Operatória , Estudos Prospectivos , Amplitude de Movimento Articular , Articulação Temporomandibular/lesões , Resultado do Tratamento
20.
Oral Maxillofac Surg ; 12(4): 195-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18682994

RESUMO

INTRODUCTION: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder with a shortened fragment of a D4Z4 repeat on chromosome 4q35. The infantile form of FSHD is relatively rare. CASE REPORT: Within this case report, we describe the orthognatic surgery in a patient with infantile FSHD to diminish the functional and esthetic disturbances in the orofacial region. We saw a 20-year-old female patient suffering from infantile FSHD with remarkable macroglossia and frontal open bite. Diagnosis was based on molecular genetic investigations. To improve the functions of the stomatognathic system, we performed a tongue reduction and a segment osteotomy in the frontal aspect of the mandible. The patient was satisfied with the functional and esthetic results. Lip competence and occlusion were significantly improved. Thus, orthognatic surgery can enhance oral function, facial esthetics, and general quality of life.


Assuntos
Glossectomia/métodos , Macroglossia/cirurgia , Distrofia Muscular Facioescapuloumeral/cirurgia , Mordida Aberta/cirurgia , Idade de Início , Cromossomos Humanos Par 4 , Feminino , Humanos , Macroglossia/etiologia , Mandíbula/cirurgia , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/genética , Mordida Aberta/etiologia , Deleção de Sequência , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...