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1.
Surg Case Rep ; 10(1): 96, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652337

RESUMO

BACKGROUND: Myofibromas are rare mesenchymal tumors with a predilection for the head, neck, and oral cavity. Primarily affecting infants and young children, these tumors typically manifest as superficial painless nodules. Diagnosis is confirmed through histopathological examination of a biopsy, revealing nodules characterized by spindle cell proliferation. To our knowledge, only two cases of pinna myofibroma have been previously reported in the literature. CASE PRESENTATION: Here, we present the case of a three-year-old male who developed a myofibroma of the left auricle following trauma to the area one year earlier. The patient underwent surgical resection without any postoperative complications. The patient later returned with a lesion consistent with hypertrophic scar. CONCLUSIONS: This study aims to provide a comprehensive review of the clinical presentation, histopathologic and immunohistochemical features, and surgical management of this unique case of myofibroma of the pinna.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38613193

RESUMO

OBJECTIVE: To measure postoperative airway volumes among patients with craniofacial abnormalities and compare them to normative values. STUDY DESIGN: Retrospective, comparative study. SETTING: Academic Medical Center. METHODS: Retrospective analysis of imaging of children with craniofacial abnormalities treated at NYU Langone Health from January 2013 to February 2021. Upper airway volumes postcraniofacial surgery were measured using 3D processing software (Dolphin 3D, version 11.95). These values were compared with published normative values. RESULTS: Twenty-one subjects were identified and compared to normative values. The postoperative oropharyngeal volumes were on average 43.7% smaller than the normative values (P < .001), and the total upper airway volumes were 31.6% smaller (P = .003). No significant differences were observed in the nasopharyngeal or hypopharyngeal volumes of the study cohort compared to the normative data. Among children ages 12 to 17 years (n = 13), the mean oropharyngeal volumes were 47.6% smaller than normal (P < .001), and the mean total upper airway volumes were 34.6% smaller than normal (P < .001). Among children ages 7 to 11 years (n = 8), the mean oropharyngeal volumes were 35.1% smaller than normal (P = .049), but no difference in mean total upper airway volume was observed. CONCLUSION: In children with craniofacial anomalies, postoperative airway volumes remain lower than normative values. However, even a slight increase in airway volume can yield a substantial increase in flow rate. 3D airway evaluations are a valuable tool for surgical planning and analysis and can help with optimizing airway dynamics.

3.
Laryngoscope ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014817

RESUMO

OBJECTIVE(S): Previous literature has established a high prevalence of upper airway obstruction in children with craniofacial abnormalities. This study aims to perform quantitative airway volume measurements in patients with craniofacial abnormalities and compare them to age and sex-matched controls. METHODS: We performed a retrospective review of the records of all children with craniofacial abnormalities who underwent head-and-neck computed tomography (CT) imaging at a single tertiary-care center between 1/1/13 and 12/31/20 using the ICD-10 codes Q75.1, Q75.4, and Q87.0. These patients were then matched by age and sex to patients with isolated craniosynostosis (Q75.0). CT scans were imported into Dolphin Imaging software, and airway volumes were measured for the nasal cavity, nasopharynx, oropharynx, and hypopharynx. The primary outcome was the total airway volume, defined as the sum of these measurements. RESULTS: Thirty subjects with craniofacial syndromes were matched to 30 patients with isolated craniosynostosis (controls). In both groups, 18 subjects (60%) were male (p = 0.99). The average ages for syndromic patients and controls were 12.1 and 12.9 months, respectively (p = 0.84). On average, the total airway volumes of syndromic patients were 25% lower than those of controls (p = 0.02). Syndromic patients had 39% smaller nasal cavity volumes (p < 0.001) and 32% smaller nasopharyngeal volumes (p < 0.01). Significant volume differences were not observed for the oropharynx or hypopharynx. CONCLUSION: We present a unique technique to measure airway volumes in patients with craniofacial abnormalities. These findings will help practitioners to further understand the anatomy and pathophysiology of disturbed breathing in children with craniofacial syndromes. LEVEL OF EVIDENCE: III Laryngoscope, 2023.

5.
Methods Mol Biol ; 455: 3-18, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18463807

RESUMO

Osteoblasts are the cells responsible for formation of new bone throughout life. Rats are one of the most widely studied mammalian species in skeletal biology and serve as useful models for many aspects of human skeletal physiology. The availability of genetically modified mice as research tools has greatly enabled our understanding of how specific genes contribute to the process of skeletogenesis. In order to explore the impact of biochemical, genetic, or pharmacological manipulation on bone formation, various osteogenic cell culture systems have been developed. Two of the most widely accepted rodent osteogenic culture models, using osteoprogenitor cells isolated from calvaria or bone marrow, are described in this chapter.


Assuntos
Técnicas de Cultura de Células , Osteoblastos/citologia , Células-Tronco/citologia , Animais , Biomarcadores/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Calcificação Fisiológica , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos , Osteoblastos/fisiologia , Osteogênese/fisiologia , Ratos , Crânio/citologia
6.
Mol Nutr Food Res ; 49(9): 837-43, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15995977

RESUMO

Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones (Humulus lupulus L.). In this study, we investigated the cell growth inhibitory potential of XN on cultured human colon cancer cells. Cell proliferation was measured by sulforhodamine B staining. Poly(ADP-ribose)polymerase (PARP) cleavage, activation of caspases-3, -7, -8, and -9, and Bcl-2 family protein expression were detected by Western blot analyses. XN significantly reduced proliferation of the HCT 116-derived colon cancer cell line 40--16. Half-maximal inhibitory concentrations decreased from 4.1 microM after 24 h treatment to 3.6 and 2.6 microM after 48 and 72 h incubation, respectively. Treatment with 15 microM XN for 48 h and with 5 microM for 72 h led to the detection of the cleaved 89 kDa fragment of 116 kDa PARP as an indication of apoptosis induction. Concomitantly, we observed activation and cleavage of the effector caspases-3 and -7, induced by activation of the initiator caspases -8 and -9. Expression of anti-apoptotic Bcl-2 was down regulated when the cells were treated with XN for 48--72 h. We conclude that induction of apoptosis by downregulation of Bcl-2 and activation of the caspase cascade may contribute to the chemopreventive or therapeutic potential of XN.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Neoplasias do Colo/patologia , Mitocôndrias/efeitos dos fármacos , Propiofenonas/farmacologia , Caspase 3 , Caspase 7 , Caspase 8 , Caspase 9 , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação Enzimática , Flavonoides , Humanos , Humulus/química , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/análise
8.
Mol Nutr Food Res ; 52 Suppl 1: S28-44, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18398871

RESUMO

Apples and apple juices are widely consumed and rich sources of phytochemicals. The aim of the present study was to determine which apple constituents contribute to potential chemopreventive activities, using a bioactivity-directed approach. A polyphenol-enriched apple juice extract was fractionated by various techniques. Extract and fractions were tested in a series of test systems indicative of cancer preventive potential. These test systems measured antioxidant effects, modulation of carcinogen metabolism, anti-inflammatory and antihormonal activities, and antiproliferative potential. Regression analyses indicated that 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging potential correlated with the sum of low molecular weight (LMW) antioxidants (including chlorogenic acid, flavan-3-ols, and flavonols) and procyanidins, whereas peroxyl radicals were more effectively scavenged by LMW compounds than by procyanidins. Quercetin aglycone was identified as a potent Cyp1A inhibitor, whereas phloretin and (-)-epicatechin were the most potent cyclooxygenase 1 (Cox-1) inhibitors. Aromatase and Cyp1A inhibitory potential and cytotoxicity toward HCT116 colon cancer cells increased with increasing content in procyanidins. Overall, apple juice constituents belonging to different structural classes have distinct profiles of biological activity in these in vitro test systems. Since carcinogenesis is a complex process, combination of compounds with complementary activities may lead to enhanced preventive effects.


Assuntos
Anticarcinógenos/isolamento & purificação , Flavonoides/isolamento & purificação , Malus/química , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Bebidas , Ácidos Cafeicos/isolamento & purificação , Catequina/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Polifenóis
9.
Proc Natl Acad Sci U S A ; 104(25): 10619-24, 2007 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-17537919

RESUMO

Bone is accrued and maintained primarily through the coupled actions of bone-forming osteoblasts and bone-resorbing osteoclasts. Cumulative in vitro studies indicated that proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of osteoclast function and activity. However, our investigation of PYK2-/- mice did not reveal evidence supporting an essential function for PYK2 in osteoclasts either in vivo or in culture. We find that PYK2-/- mice have high bone mass resulting from an unexpected increase in bone formation. Consistent with the in vivo findings, mouse bone marrow cultures show that PYK2 deficiency enhances differentiation and activity of osteoprogenitor cells, as does expressing a PYK2-specific short hairpin RNA or dominantly interfering proteins in human mesenchymal stem cells. Furthermore, the daily administration of a small-molecule PYK2 inhibitor increases bone formation and protects against bone loss in ovariectomized rats, an established preclinical model of postmenopausal osteoporosis. In summary, we find that PYK2 regulates the differentiation of early osteoprogenitor cells across species and that inhibitors of the PYK2 have potential as a bone anabolic approach for the treatment of osteoporosis.


Assuntos
Quinase 2 de Adesão Focal/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese/fisiologia , Osteoporose/terapia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Diferenciação Celular , Células Cultivadas , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Knockout , Ovariectomia , Ratos , Ratos Sprague-Dawley
10.
J Biol Chem ; 281(33): 23436-44, 2006 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-16785231

RESUMO

Reduction in levels of sex hormones at menopause in women is associated with two common, major outcomes, the accumulation of white adipose tissue, and the progressive loss of bone because of excess osteoclastic bone resorption exceeding osteoblastic bone formation. Current antiresorptive therapies can reduce osteoclastic activity but have only limited capacity to stimulate osteoblastic bone formation and restore lost skeletal mass. Likewise, the availability of effective pharmacological weight loss treatments is currently limited. Here we demonstrate that conditional deletion of hypothalamic neuropeptide Y2 receptors can prevent ongoing bone loss in sex hormone-deficient adult male and female mice. This benefit is attributable solely to activation of an anabolic osteoblastic bone formation response that counterbalances persistent elevation of bone resorption, suggesting the Y2-mediated anabolic pathway to be independent of sex hormones. Furthermore, the increase in fat mass that typically occurs after ovariectomy is prevented by germ line deletion of Y2 receptors, whereas in male mice body weight and fat mass were consistently lower than wild-type regardless of sex hormone status. Therefore, this study indicates a role for Y2 receptors in the accumulation of adipose tissue in the hypogonadal state and demonstrates that hypothalamic Y2 receptors constitutively restrain osteoblastic activity even in the absence of sex hormones. The increase in bone formation after release of this tonic inhibition suggests a promising new avenue for osteoporosis treatment.


Assuntos
Envelhecimento/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Deleção de Genes , Hipotálamo/metabolismo , Orquiectomia , Receptores de Neuropeptídeo Y/deficiência , Receptores de Neuropeptídeo Y/genética , Tecido Adiposo/fisiopatologia , Envelhecimento/genética , Animais , Peso Corporal/genética , Reabsorção Óssea/genética , Reabsorção Óssea/fisiopatologia , Feminino , Fêmur/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Orquiectomia/efeitos adversos , Coluna Vertebral/fisiopatologia
12.
J Nutr ; 132(9): 2814-8, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12221251

RESUMO

Red wine is a rich source of polyphenols, which exhibit a number of biological effects in different in vitro and in vivo systems. The bioavailability of polyphenols is poor and the plasma concentrations of major red wine polyphenols are usually low after consumption of dietary relevant amounts of red wine. In contrast to most organ systems, the gastrointestinal tract (particularly the epithelial cells of this organ system) is exposed to high concentrations of polyphenols. Here, we show that the total polyphenol pool isolated from a red wine (varity Lemberger, vintage 1998) at micromolar concentrations inhibited the proliferation of transformed colon epithelial cells HT 29 clone 19A induced by epidermal growth factor (EGF). Inhibition of proliferation was also associated with modulation of activation of mitogen-activated protein kinases (MAPK). Stress activated c-Jun N-terminal kinases 1/2 (JNK) and p38 MAPK were significantly activated by red wine polyphenols (6 mmol/L). Maximum phosphorylation of both MAPK was observed after a 1-h treatment with red wine polyphenols. In contrast, activation of extracellular signal regulated kinase (ERK) 1/2 by EGF (1 nmol/L) was significantly inhibited by red wine polyphenols (6 mmol/L). This signaling pattern, activation of JNK 1/2 and p38 MAPK and inhibition of ERK 1/2, is typical for antiproliferative compounds, indicating that red wine polyphenols may inhibit the proliferation of colon carcinoma cells by modulating MAPK intracellular signal transduction pathways.


Assuntos
Flavonoides , Células HT29/efeitos dos fármacos , Fenóis/farmacologia , Polímeros/farmacologia , Vinho , Divisão Celular/efeitos dos fármacos , Células Clonais , Meios de Cultura Livres de Soro , Fator de Crescimento Epidérmico/farmacologia , Células HT29/enzimologia , Células HT29/patologia , Humanos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Polifenóis
14.
Bioorg Med Chem ; 11(4): 581-90, 2003 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-12538023

RESUMO

Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a K(i)=7 nM, rat pituicyte EC(50)=3 nM) and the des-methyl analogue 5c (hGHS-R1a K(i)=17 nM, rat pituicyte EC(50)=3 nM), increased plasma GH levels in an anesthesized rat model, with ED(50) values less than 0.05 mg/kg iv. Capromorelin showed enhanced intestinal absorption in rodent models and exhibited superior pharmacokinetic properties, including high bioavailabilities in two animal species [F(rat)=65%, F(dog)=44%]. This short-duration GHS was orally active in canine models and was selected as a development candidate for the treatment of musculoskeletal frailty in elderly adults.


Assuntos
Dipeptídeos/síntese química , Dipeptídeos/farmacologia , Hormônio do Crescimento/metabolismo , Piperidinas/síntese química , Piperidinas/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Animais , Células Cultivadas , Fenômenos Químicos , Físico-Química , DNA Complementar/metabolismo , Dipeptídeos/farmacocinética , Cães , Desenho de Fármacos , Feminino , Meia-Vida , Humanos , Indicadores e Reagentes , Indóis/farmacologia , Espectroscopia de Ressonância Magnética , Piperidinas/farmacocinética , Hipófise/citologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Pirazóis/farmacocinética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Solubilidade , Compostos de Espiro/farmacologia
15.
Bioorg Med Chem Lett ; 12(22): 3279-82, 2002 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-12392732

RESUMO

New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma IGF-1 levels. Compounds 4c and 4d (ACD LogD values >or=2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED(50)s>10 mg/kg). A less lipophilic derivative 4 (ACD LogD=1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty.


Assuntos
Piperidinas/farmacocinética , Pirazóis/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Cães , Hormônio do Crescimento/efeitos dos fármacos , Substâncias de Crescimento/metabolismo , Meia-Vida , Interações Hidrofóbicas e Hidrofílicas , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Piperidinas/administração & dosagem , Piperidinas/síntese química , Pirazóis/administração & dosagem , Pirazóis/síntese química , Ratos , Ratos Wistar , Relação Estrutura-Atividade
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