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2.
J Craniofac Surg ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506523

RESUMO

OBJECTIVE: Crouzon syndrome with acanthosis nigricans (CAN) is caused by the specific mutation c.1172C>A (p.Ala391Glu) in the fibroblast growth factor receptor 3 gene, and has an estimated prevalence of 1:1,000,000 births. Most cases occur de novo; however, autosomal dominant inheritance may occur. The clinical presentation typically includes craniosynostosis, midface and maxillary hypoplasia, choanal atresia/stenosis, hydrocephalus, and intracranial hypertension. Patients develop acanthosis nigricans, a hyperkeratotic skin disorder. The authors present the first known study to investigate the speech, language, hearing, and feeding of patients with CAN. METHODS: A retrospective case-note review of patients with a genetically confirmed diagnosis of CAN attending the Oxford Craniofacial Unit during a 36-year period (1987-2023) was undertaken. RESULTS: Participants were 6 patients with genetically-confirmed CAN (5 females, 1 male), all cases arose de novo. All patients had craniosynostosis (n = 5/6 multisuture synostosis, n = 1/6 left unicoronal synostosis). Hydrocephalus was managed through ventriculoperitoneal shunt in 67% (n = 4/6) of patients, and 67% (n = 4/6) had a Chiari 1 malformation. Patients had a complex, multifactorial feeding history complicated by choanal atresia/stenosis (100%; n = 6/6), and significant midface hypoplasia. All patients required airway management through tracheostomy (83%; n = 5/6); and/or continuous positive airway pressure (67%; n = 4/6). All patients underwent adenotonsillectomy (100%; n = 6/6). Initial failure to thrive, low weight, and/or height were seen in 100% (n = 6/6) patients; 80% (n = 4/5) had reflux; 100% (n = 6/6) had nasogastric, or percutaneous endoscopic gastrostomy based feeding during their treatment journey. All patients had hearing loss (100%; n = 6/6). Early communication difficulties were common: receptive language disorder (50%; n = 3/6); expressive language disorder (50%; n = 3/6); and speech sound disorder in 50% (n = 3/6)-necessitating the use of Makaton in 80% of patients (n = 3/5). CONCLUSIONS: Patients with CAN experience significant respiratory, neurological, and structural obstacles to hearing, speech, language, and feeding. The authors present a recommended pathway for management to support patients in these domains.

3.
J Craniofac Surg ; 35(1): 104-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38011637

RESUMO

INTRODUCTION: Historically, medical professionals have been the providers of specialist information about rare medical conditions. Now, increasingly, patients and the public are using the internet to access and generate information about medical diagnoses. The global nature of the internet allows patients to connect across geographical borders, and to obtain and share information that would have been previously inaccessible to them. This research investigated the use of website and social media by parents of children with craniosynostosis. METHODS: A cross-sectional survey-based design was employed. Participants were parents of children with craniosynostosis attending multidisciplinary craniofacial clinics within the Oxford Craniofacial Unit. A questionnaire was administered which assessed social media and website use adapted from the questionnaire created by Khouri and colleagues (2016) and Huggons and colleagues (2019). The surveys were administered over an 18-month period (November 2020 to May 2022). RESULTS: The final sample comprised 82 parents [70 mothers; 10 fathers; 1 sister/carer and 1 parent (mother/father unspecified)]. The children were aged 11 months-16 years of age (average age 6 y and 3 mo). Children had a variety of diagnoses: 31 sagittal, 19 metopic, 14 syndromic craniosynostosis, 8 unicoronal, 6 multisuture, 3 bicoronal, and 1 unilambdoid.Results showed that 93% (n=76/82) of parents used the internet to find out more about craniosynostosis, with 72% (n=59/82) of parents specifically using social media to find out more about craniosynostosis. The social media platforms used included: Facebook 64% (n=53/82), Instagram 24% (n=20/82), Blogs 12% (n=10/82), Twitter 4% (n= 4/82), Tik Tok 2% (n=2/82), and Snapchat 0.01% (n=1/82).Parents reported that Facebook was the most helpful source of information about craniosynostosis (52%; n=43/82). Parents indicated the key timepoints they used social media included: when their child received a diagnosis (70%; n=58/82), before their child's surgery (34%; n=28/82), before their first craniofacial clinic appointment (83%; n=25/30), and when child was older (17%; n=14/84). Forty percent (n=33/82) of parents said that a diagnosis of craniosynostosis made no difference to their social media use, whereas 34% (n=28/82) of parents used social media more, and 20% (n=16/82) used it less. CONCLUSION: Results highlight that parents use social media and other websites to access information relating to craniosynostosis. Future research should examine whether parental use of social media changes across their child's lifespan and evaluate the quality of this information.


Assuntos
Craniossinostoses , Mídias Sociais , Criança , Feminino , Humanos , Cuidadores , Estudos Transversais , Pais , Doenças Raras
5.
J Craniofac Surg ; 32(6): 2035-2040, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770046

RESUMO

BACKGROUND: Patients, parents, and carers are increasingly using social media to access and contribute to health information. There are currently 3.484 billion active social media users. Instagram is a primarily visual social media platform for sharing photographs and videos with currently over one billion monthly active users. Limited research has investigated the use of Instagram in healthcare contexts including plastic surgery, and in the treatment of specific conditions, such as fibromyalgia and scoliosis. This study aimed to investigate the use of Instagram in relation to craniofacial surgery. METHODS: The authors investigated the use of 12 Instagram craniofacial surgery-related hashtags. Quantitative and qualitative data were collected for each of the "top" nine posts associated with each hashtag. Duplicate posts, posts not in English and those not relevant to craniofacial surgery were excluded.Thematic analysis was then used to qualitatively evaluate the captions and comments of each of the nine "top" posts associated with each hashtag. RESULTS: A total number of 151,738 posts were identified using the 12 hashtags queried in the present study, with #craniofacial being the most popular hashtag (87% of posts). Parents (n = 25, 33%) and surgeons (n = 25, 33%) were responsible for the majority of posts. A heterogenous group were responsible for the remaining 34% of posts.Results indicated that parents and surgeons posted significantly different images (chi-squared with Yates correlation is 25.0519, P  < 0.00001). Parents' posts were predominantly images of their child/patients (n = 24) compared to posts about patients by surgeons (n = 6). Posts by surgeons were predominantly images of professionals (n = 14) compared to images of professionals posted by parents (n = 1).Results of qualitative analysis of captions of posts indicated a significant difference in themes that emerged between parents and surgeons; with surgeons largely using Instagram for information giving, and parents for sharing of experiences (chi-square (n = 108) = 40.83, P  < 0.00001).There was a significant difference (two-tailed t test, P  = 0.002) in engagement (measured by the number of likes on posts) on posts by parents (mean = 3778) compared to posts by surgeons (mean = 135.4). CONCLUSIONS: Results indicate that craniofacial-surgery related posts on Instagram provide a medium to allow individuals and families with rare disorders to connect and share their experiences. The use of Instagram to share information about craniofacial abnormalities via Instagram has the potential to be used by healthcare professionals to educate and support patients and families.


Assuntos
Procedimentos de Cirurgia Plástica , Mídias Sociais , Cirurgiões , Cirurgia Plástica , Criança , Humanos , Pais
6.
J Craniofac Surg ; 30(1): 110-114, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30394969

RESUMO

Pycnodysostosis (PYCD) is a rare autosomal-recessive skeletal disorder that typically presents with osteosclerosis of the majority of the postcranial skeleton and osteolysis of the calvarium, manifesting as persistent open cranial fontanelles and widely spaced cranial sutures. Craniosynsostosis in PYCD is a somewhat paradoxical feature, and has only been rarely reported. The authors present a unique case of a 6-year-old girl with PYCD, multisuture craniosynostosis involving the coronal and sagittal sutures, severe obstructive sleep apnoea, and raised intracranial pressure presenting as papilledema. She underwent a frontofacial monobloc distraction advancement which successfully corrected her papilledema and obstructive sleep apnoea.Pycnodysostosis is caused by a loss of function mutation in the CTSK gene that codes for the lysosomal cysteine protease, cathepsin K (CTSK). Loss of CTSK impairs the ability of osteoclasts to degrade bone extracellular matrix. Differences in osteoclast phenotype and extracellular matrix composition between membranous and cartilaginous bone may explain the clinical features of PYCD. Animal model studies suggest that craniosynostosis may arise due to variations in patient genetic background.


Assuntos
Craniossinostoses/cirurgia , Papiledema/etiologia , Picnodisostose/cirurgia , Apneia Obstrutiva do Sono/etiologia , Criança , Craniossinostoses/complicações , Feminino , Humanos , Hipertensão Intracraniana/etiologia , Osteogênese por Distração , Picnodisostose/complicações
7.
Int J Surg ; 41: 127-133, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28366760

RESUMO

BACKGROUND: Tumour necrosis factor alpha (TNF-α) is a cytokine elevated in inflammatory bowel disease enterocutaneous fistula (IBD ECF). Dendritic cells are antigen presenting cells that orchestrate the immune responses and regulate the production of cytokines by immune cells including T cells. No study to date has assessed the level of TNF-α or the presence of dendritic cells in non-IBD ECF. The aim of this study was to assess the inflammatory activity, with a particular emphasis on TNF-α in non-IBD ECF when compared with control small bowel tissue. METHODS: Tissue biopsies were obtained from ECF at operation from non-IBD patients and from terminal ileum in normal colonoscopy control patients. After overnight culture, accumulation of intracellular TNF-α was measured by flow cytometry in cells treated with monensin to assess the on-going cytokine production. Data were acquired using FACS Canto II. Unpaired Student's t-test was used to compare variables between groups and p < 0.05 was regarded as significant. RESULTS: The on-going production of TNF-α from dendritic cells (p = 0.0007), putative monocyte and B cell populations (p = 0.04) and CD3+ T cells (p = 0.04) was significantly higher in non-IBD ECF tissue than that from control tissue. CONCLUSIONS: This study reveals results which provide evidence for the potential use of anti-TNF-α agents in the treatment of non-IBD ECF. A pilot study to evaluate this treatment as an alternative option in an already surgically challenging group of patients is planned. Positive findings would be a major medical advance with a new use for anti-TNF-α agents.


Assuntos
Células Dendríticas/imunologia , Fatores Imunológicos/análise , Fístula Intestinal/imunologia , Fator de Necrose Tumoral alfa/análise , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Íleo/imunologia , Íleo/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Projetos Piloto , Linfócitos T/imunologia
8.
J Craniofac Surg ; 27(6): 1543-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27438438

RESUMO

The squamosal suture is one of the lateral minor skull sutures, separating the parietal and squamous temporal bones. While the phenotypic appearances and sequelae of synostosis of the major cranial vault sutures are well documented, little is reported concerning synostosis of the squamosal suture (SQS). The aim of this study was to determine the frequency of squamosal suture synostosis, and to document the significance of this entity.A retrospective review of the diagnostic imaging for all new pediatric patients (aged ≤16 years) referred to the Oxford Craniofacial Unit between January 2008 and February 2013 was completed to identify patients with SQS. Computed tomography (CT) imaging was available in 422 patients and the axial and three-dimensional reconstructed images reviewed.Squamosal suture synostosis was confirmed in 38 patients (9%). It was present in conjunction with major suture synostosis in 33 patients and in isolation in 5. The incidence increased with age. It was more common in patients with syndromic craniosynostosis (18%) and associated syndromic conditions (36%) than in those with isolated major suture synostosis (6%). It was found to occur with coronal, lambdoid, and sagittal synostosis, but was most frequent with multisuture fusion patterns. Squamosal suture synostosis was not associated with a consistent calvarial deformity either in isolation or when associated with a major suture fusion. No patient underwent surgery specifically to correct SQS.In conclusion, contrary to previous reports, squamosal suture synostosis is a relatively frequent finding in the general case mix of a typical craniofacial unit, but is of limited clinical significance.


Assuntos
Craniossinostoses , Adolescente , Criança , Pré-Escolar , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/epidemiologia , Craniossinostoses/patologia , Humanos , Imageamento Tridimensional , Estudos Retrospectivos , Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
J Neurosurg Pediatr ; 15(4): 350-60, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25559921

RESUMO

OBJECT Raised intracranial pressure (ICP) is recognized to occur in patients with nonsyndromic isolated sagittal craniosynostosis (SC) prior to surgery. However, the incidence of raised ICP following primary surgery is rarely reported and there appears to be a widely held assumption that corrective surgery for SC prevents the later development of intracranial hypertension. This study reports the incidence of postoperative raised ICP in a large cohort of patients with SC treated by 1 of 2 surgical procedures in a single craniofacial unit. METHODS A retrospective review was performed of all patients with SC who underwent either a modified strip craniectomy (MSC) or calvarial remodeling (CR) procedure under the care of the Oxford Craniofacial Unit between 1995 and 2010 and who were followed up for more than 2 years. The influence of patient age at surgery, year of surgery, sex, procedure type, and the presence of raised ICP preoperatively were analyzed. RESULTS Two hundred seventeen children had primary surgery for SC and were followed up for a mean of 86 months. The overall rate of raised ICP following surgery was 6.9%, occurring at a mean of 51 months after the primary surgical procedure. Raised ICP was significantly more common in those patients treated by MSC (13 of 89 patients, 14.6%) than CR (2 of 128 patients, 1.6%). Also, raised ICP was more common in patients under 1 year of age, the majority of whom were treated by MCS. No other factor was found to have a significant effect. CONCLUSIONS Postoperative raised ICP was found in more than 1 in 20 children treated for nonsyndromic SC in this series. It was significantly influenced by the primary surgical procedure and age at primary surgery. Careful long-term follow-up is essential if children who develop raised ICP following surgery are not to be overlooked.


Assuntos
Craniossinostoses/cirurgia , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Crânio/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Hipertensão Intracraniana/fisiopatologia , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos
11.
J Craniofac Surg ; 26(1): 19-25, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25569384

RESUMO

Correction of scaphocephaly is one of the principle goals of surgery in sagittal craniosynostosis. Reported relapse in head shape after surgery and continued head growth into late adolescence underscores the need for long-term outcomes to be considered when comparing between different surgical approaches in this condition; yet there are relatively few reports of results to 5 years and beyond in the literature. Therefore, a retrospective review was performed of the anthropometric data of 224 patients with sagittal craniosynostosis who underwent primary surgery between 1994 and 2012. During this period, patients underwent either a modified strip craniectomy (MSC) or calvarial remodeling (CR) procedure. Sixty-two patients were treated by MSC and followed up for a mean of 44 months. One hundred sixty-two patients had CR, with follow-up for a mean of 45 months. Overall, 90 patients were seen up to 5 years, and 47 patients to 9 years or more after surgery. The cephalic index (CI) of MSC-treated patients improved from a mean of 67.0 to 72.7, with 31% achieving a CI greater than 75 at one year. Calvarial remodeling was significantly more effective at correcting the scaphocephalic deformity. Patients treated with CR improved from a mean CI of 66.7 to 76.1. Sixty-two percent of the patients achieved a CI greater than 75. In both groups, outcomes were stable throughout follow-up with no significant relapse up to 14 years after surgery.


Assuntos
Craniossinostoses/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Cefalometria/métodos , Criança , Pré-Escolar , Craniotomia/métodos , Feminino , Seguimentos , Osso Frontal/crescimento & desenvolvimento , Osso Frontal/cirurgia , Humanos , Lactente , Estudos Longitudinais , Masculino , Osso Occipital/crescimento & desenvolvimento , Osso Occipital/cirurgia , Osso Parietal/crescimento & desenvolvimento , Osso Parietal/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
12.
J Neurosurg Pediatr ; 14(6): 674-81, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25259602

RESUMO

OBJECT: The presence of raised intracranial pressure (ICP) in untreated nonsyndromic, isolated sagittal craniosynostosis (SC) is an important functional indication for surgery. METHODS: A retrospective review was performed of all 284 patients presenting with SC to the Oxford Craniofacial Unit between 1995 and 2010. RESULTS: Intraparenchymal ICP monitoring was performed in 39 children following a standard unit protocol. Monitoring of ICP was offered for all patients in whom nonoperative management was considered on the basis of minimal deformity or in cases in which parents were reluctant to agree to corrective surgery. These patients presented at an older age than the rest of the cohort (mean age 56 months), with marked scaphocephaly (16/39, 41%), mild scaphocephaly (11, 28%), or no scaphocephalic deformity (12, 31%). Raised ICP was found in 17 (44%) patients, with no significant difference in its incidence among the 3 different deformity types. Raised ICP was not predicted by the presence of symptoms of ICP or developmental delay or by ophthalmological or radiological findings. CONCLUSIONS: The incidence of raised ICP in SC reported here is greater than that previously published in the literature. The lack of a reliable noninvasive method to identify individuals with elevated ICP in SC mandates consideration of intraparenchymal ICP monitoring in all patients for whom nonoperative management is contemplated.


Assuntos
Craniossinostoses/complicações , Hipertensão Intracraniana/epidemiologia , Pressão Intracraniana , Período Pré-Operatório , Adolescente , Criança , Pré-Escolar , Craniossinostoses/fisiopatologia , Craniossinostoses/cirurgia , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Lactente , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/fisiopatologia , Masculino , Estudos Retrospectivos
13.
J Craniofac Surg ; 25(5): 1721-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25162545

RESUMO

INTRODUCTION: Posterior distraction (PD) is rapidly emerging as an important technique to increase the intracranial volume and correct calvarial morphology in patients with severe brachycephaly or turribrachycephaly. METHODS: A retrospective review was performed of all 31 patients who underwent PD at the Oxford Craniofacial Unit between 2007 and 2012. RESULTS: Twenty-three patients (74.2%) underwent PD as a primary procedure at a median age of 8 months. Eight patients (25.8%) had PD as a secondary transcranial procedure at a median age of 48 months. Full distraction to 20 mm was achieved in 28 patients (90.3%). Of these, all but 1 demonstrated a significant improvement in morphology, with a resolution of the symptoms and signs of raised intracranial pressure in all proven to have it preoperatively. Unanticipated events occurred in 61.3% of patients, with 19.4% undergoing one or more unplanned procedures. Wound infection (29.0%) and tissue necrosis (22.6%) were the commonest. Cerebrospinal fluid leaks were rarer (6.5%) but prevented full distraction. Nine patients (29.0%) had a consolidation period of less than 30 days without experiencing relapse. In 11 patients who had a later fronto-orbital advancement and remodeling, wound closure was tight, resulting in dehiscence in 3 cases (27.3%). CONCLUSIONS: Posterior distraction is an effective procedure in the management of severe brachycephaly or turribrachycephaly but has associated risks. Our protocol has evolved with experience to favor a reduced latency period and consolidation phase and the use of 2 distractor devices.


Assuntos
Osteogênese por Distração/métodos , Crânio/cirurgia , Acrocefalossindactilia/cirurgia , Vazamento de Líquido Cefalorraquidiano/etiologia , Criança , Pré-Escolar , Disostose Craniofacial/cirurgia , Craniossinostoses/cirurgia , Craniotomia/métodos , Feminino , Seguimentos , Humanos , Lactente , Hipertensão Intracraniana/cirurgia , Masculino , Necrose , Osteogênese por Distração/instrumentação , Estudos Retrospectivos , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/etiologia
15.
Cleft Palate Craniofac J ; 49(6): 708-13, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21848369

RESUMO

OBJECTIVE: This study was performed to investigate whether nasal and oropharyngeal microbiological swabs taken prior to cleft lip and palate surgery correlated with the oronasal flora at the time of surgery and whether specific culture results affected surgical outcome. METHODS: Prospective audit set in two designated U.K. cleft centers each with a single surgeon. Nasal and oropharyngeal microbiological swabs were taken within 2 weeks prior to surgery and again on the operating table. Adverse outcome measures included postoperative pyrexia, wound dehiscence, or fistula formation. RESULTS: One hundred forty-four cases were recruited over 12 months. Nasal swabs cultured organisms significantly more often than oropharyngeal swabs (p < .0001). No significant difference was detected in the number of cases with a positive microbiology culture preoperatively compared with perioperative sampling (48% and 50%). The specific organisms cultured from preoperative swabs were the same as those cultured at surgery in only half of cases. Preoperative microbiology swabs were poorly predictive of the oronasal flora at surgery. Antibiotic treatment of patients with positive preoperative microbiology did not significantly reduce the incidence of bacterial colonization or significantly alter clinical outcome. CONCLUSION: Preoperative microbiological investigation is not helpful in predicting the nasal and oropharyngeal flora at the time of surgery. Further, culture results did not correlate with postoperative outcome, regardless of whether pre- or perioperative antibiotic therapy was instigated. This evidence suggests that microbiology screening swabs are an unnecessary investigation.


Assuntos
Fenda Labial/microbiologia , Fenda Labial/cirurgia , Fissura Palatina/microbiologia , Fissura Palatina/cirurgia , Antibioticoprofilaxia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Deiscência da Ferida Operatória/microbiologia , Deiscência da Ferida Operatória/prevenção & controle , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Reino Unido
17.
Am J Pathol ; 171(6): 2048-57, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18055559

RESUMO

De novo tissue generation stimulated by three angiogenic growth factors administered in a factorial design was studied in an in vivo murine tissue engineering chamber. A silicone chamber was implanted around the epigastric pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular endothelial growth factor-120 (VEGF120), recombinant human basic fibroblastic growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF-BB) added as single, double, or triple combinations. Angiogenesis, supporting tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically enhanced by VEGF120 + FGF-2 (P = 0.019). FGF-2 (P = 0.008) and PDGF-BB (P = 0.01) significantly increased connective tissue/inflammatory cell infiltrate (macrophages, pericytes, and preadipocytes) in double and triple combinations compared with control. At 6 weeks sequential addition of growth factors increased the percent volume of adipose tissue (P < 0.0005, each main effect), with a synergistic increase in adipose tissue in combination treatments (P < 0.0005). Groups containing 300 ng/ml of single growth factors produced significantly less adipose tissue than the triple growth factor combination (P < 0.0005, VEGF120 and PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations increased early angiogenesis and cell infiltration resulting in synergistically increased adipose tissue growth at 6 weeks. Two way and higher level synergies are likely to be important in therapeutic applications of angiogenic growth factors.


Assuntos
Adipogenia/efeitos dos fármacos , Indutores da Angiogênese/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Vasos Sanguíneos/citologia , Vasos Sanguíneos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Camundongos , Modelos Animais , Ratos , Engenharia Tecidual
18.
Stem Cells ; 25(7): 1730-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17395770

RESUMO

Growth hormone (GH) deficiency is a significant clinical problem, since growth hormone is essential for the regulation of growth, metabolism, and the cardiovascular system. Stem and progenitor cells have been identified in many adult tissues. Recently, our laboratory identified a cell type within the adult pituitary gland with stem cell-like properties, which we have termed pituitary colony-forming cells (PCFCs). Herein we investigate the ability of PCFCs to survive and differentiate in vivo. Enriched populations of PCFCs were transplanted into an in vivo microchamber model. Grafts were harvested at 6 weeks post-transplant and tested for surviving donor cells (LacZ(+)) or for differentiation (GH(+)). The results showed that donor cells survived in chambers (LacZ(+)) and underwent division (phosphohistone-H3-positive). Furthermore, grafted cells showed colocalization of LacZ and GH, suggesting differentiation. To confirm differentiation, donor cells were obtained from a GH-enhanced green fluorescent protein (eGFP) reporter transgenic mouse model that expressed eGFP under control of the GH promoter. Cells that were eGFP(-), that is, GH(-), were selected by fluorescence-activated cell sorting (FACS) and transplanted. After 6 weeks, eGFP(+)GH(+) cells were detected in grafts by immunostaining and by FACS analysis of digested grafts. In conclusion, PCFCs have the capacity to divide and differentiate into GH(+) cells in vivo. The vascularized tissue chamber model is an ideal model to investigate the environmental niche for PCFC expansion and differentiation and has the potential to be developed into a growth hormone-releasing organoid in vivo. Disclosure of potential conflicts of interest is found at the end of this article.


Assuntos
Diferenciação Celular , Hipófise/citologia , Células-Tronco/citologia , Animais , Sobrevivência Celular , Feminino , Citometria de Fluxo , Genes Reporter , Sobrevivência de Enxerto , Hormônio do Crescimento/metabolismo , Masculino , Camundongos , Camundongos SCID , Camundongos Transgênicos , Transplante de Células-Tronco
19.
Obesity (Silver Spring) ; 15(12): 2951-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18198303

RESUMO

OBJECTIVE: An increasing body of evidence is emerging linking adipogenesis and inflammation. Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. If inflammation can, in turn, increase adipose tissue growth, this may be the basis for a positive feedback loop in obesity. We have developed a tissue engineering model for growing adipose tissue in the mouse that allows quantification of increases in adipogenesis. In this study, we evaluated the adipogenic potential of the inflammogens monocyte chemoattractant protein (MCP)-1 and zymosan-A (Zy) in a murine tissue engineering model. RESEARCH METHODS AND PROCEDURES: MCP-1 and Zy were added to chambers filled with Matrigel and fibroblast growth factor 2. To analyze the role of inducible nitric oxide synthase (iNOS), the iNOS inhibitor aminoguanidine was added to the chamber. RESULTS: Our results show that MCP-1 generated proportionally large quantities of new adipose tissue. This neoadipogenesis was accompanied by an ingrowth of macrophages and could be mimicked by Zy. Aminoguanidine significantly inhibited the formation of adipose tissue. DISCUSSION: Our findings demonstrate that low-grade inflammation and iNOS expression are important factors in adipogenesis. Because fat neoformation in obesity and the metabolic syndrome is believed to be mediated by macrophage-derived proinflammatory cytokines, this adipose tissue engineering system provides a model that could potentially be used to further unravel the pathogenesis of these two metabolic disorders.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Quimiocina CCL2/farmacologia , Óxido Nítrico/farmacologia , Obesidade/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Obesidade/metabolismo , Engenharia Tecidual/métodos , Zimosan/farmacologia
20.
Tissue Eng ; 12(11): 3035-43, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17518619

RESUMO

Adipose tissue forms when basement membrane extract (Matrigel) and fibroblast growth factor-2 (FGF-2) are added to our mouse tissue engineering chamber model. A mouse tumor extract, Matrigel is unsuitable for human clinical application, and finding an alternative to Matrigel is essential. In this study we generated adipose tissue in the chamber model without using Matrigel by controlled release of FGF-2 in a type I collagen matrix. FGF-2 was impregnated into biodegradable gelatin microspheres for its slow release. The chambers were filled with these microspheres suspended in 60 microL collagen gel. Injection of collagen containing free FGF-2 or collagen containing gelatin microspheres with buffer alone served as controls. When chambers were harvested 6 weeks after implantation, the volume and weight of the tissue obtained were higher in the group that received collagen and FGF-2 impregnated microspheres than in controls. Histologic analysis of tissue constructs showed the formation of de novo adipose tissue accompanied by angiogenesis. In contrast, control groups did not show extensive adipose tissue formation. In conclusion, this study has shown that de novo formation of adipose tissue can be achieved through controlled release of FGF-2 in collagen type I in the absence of Matrigel.


Assuntos
Tecido Adiposo/fisiologia , Colágeno Tipo I/metabolismo , Preparações de Ação Retardada , Matriz Extracelular/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Engenharia Tecidual/métodos , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/transplante , Animais , Materiais Biocompatíveis/metabolismo , Soluções Tampão , Fator 2 de Crescimento de Fibroblastos/farmacologia , Gelatina/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microesferas , Fatores de Tempo
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