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1.
Ear Nose Throat J ; : 1455613241251980, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708589

RESUMO

Objectives: Substernal goiters often require surgery, yet their location presents challenges. Most can be removed via transcervical approach, but extent and relationship to mediastinal structures can merit consideration of sternotomy and assistance of colleagues. Despite widespread use in sinus surgery and previous literature reports, microdebrider use to facilitate transcervical removal of substernal goiters has not been broadly adopted. Our objective was to report our experience with use of the soft tissue shaver to facilitate substernal goiter deliver through a cervical incision in a community-based thyroidectomy practice. Methods: We reviewed thyroidectomy cases performed by a general otolaryngologist (D.M.Y.) in a community setting from January 2017 through December 2019. Four patients required microdebrider use for intracapsular debulking of substernal goiter to allow for transcervical removal. We discuss pre- and perioperative considerations, present computed tomography (CT) and operative images, review surgical technique, and report estimated blood loss (EBL), surgical time (T), complications, and length of stay. Results: Average EBL was 237.5 ml (range 100-500 ml). Average T was 137 minutes (range 121-170 minutes). No patients required sternotomy. One patient developed postoperative hematoma requiring evacuation and cautery of a bleeding site. No other complications were encountered, all patients were discharged after overnight observation. Conclusions: The microdebrider can be safely utilized by general otolaryngologists to facilitate transcervical removal of substernal goiters. Adoption of this familiar tool for a different surgical application can reduce the need for sternotomy, assistance of colleagues, or referral to a tertiary care center, with associated decrease in risk, morbidity, surgical time, length of stay, and cost, and improved patient convenience and satisfaction.

2.
Ear Nose Throat J ; : 1455613241235538, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424691

RESUMO

Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep disorder that can increase the risk of hypertension, diabetes, obesity, and cardiovascular diseases. Hypoglossal nerve stimulation (HGNS) is an alternative therapy for OSA in patients who cannot tolerate continuous positive airway pressure. Understanding the impact of HGNS on blood pressure, hemoglobin A1C (A1C), and body mass index (BMI) currently remains limited. Methods: A retrospective review study of HGNS outcomes at a single practice from January 2020 to November 2022 was conducted. Inclusion/exclusion criteria were based on HGNS eligibility and postoperative titration study. Statistical analysis and data management were performed using statistical software, R (v.4.2.1; R Core Team). Paired Student's T test, Fisher's exact test, and McNemar's exact test were utilized for statistical analysis. P values less than .05 were considered statistically significant. Results: Sixty-three patients were included in this study. A significant decrease in mean apnea-hypopnea index was noted following HGNS (mean change -28; P < .0001). Similar significant decreases were also seen in mean arterial pressures (mean change -8.4, P < .0001). There was a significant change in overall antihypertensive medication requirements and in requirements ≥3 medications (P < .0005, P = .03). There was a trend toward reduction in A1C; however, there was no change in BMI or number of diabetes medications taken. Conclusions: Our results reinforce previous findings that HGNS is an effective treatment option for carefully selected patients with OSA. In addition, our findings suggest that HGNS may improve patients' quality of life while minimizing OSA associated morbidity.

3.
Ear Nose Throat J ; : 1455613221112761, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939505

RESUMO

INTRODUCTION: Despite the presence of a growing body of literature suggesting cost-ineffectiveness of routine pathologic analysis of tonsillectomy specimens, little is known about common institutional policies and practice patterns of pediatric otolaryngologists. The objectives of this study were to determine the prevalence of routine pathological evaluation of tonsillectomy specimens for uncomplicated pediatric adenotonsillectomy procedures and to evaluate opinions regarding this controversy among board-certified pediatric otolaryngologists. METHODS: This was a cross-sectional survey study sent to board-certified pediatric otolaryngologists currently practicing and registered with the American Society of Pediatric Otolaryngology (ASPO) assessing their institutions' or practices' current policies on sending routine tonsillectomy specimens for pathology, their experience with this practice, and their opinions on whether routine pathologic analysis should be employed. Basic statistical analysis was then conducted. RESULTS: Respondents mostly practiced in an academic setting (68.4%), with the next most common being academically affiliated private practice (21.8%), and private practice was the least common (9.8%). Most respondents (85.1%) did not agree with routine pathologic analysis of otherwise uncomplicated pediatric tonsillectomy specimens. CONCLUSION: Most pediatric otolaryngologists who responded to this survey do not support routine pathological analysis of otherwise uncomplicated pediatric tonsillectomy specimens. However, the results are likely biased and should be interpreted carefully, since only a small percentage of pediatric otolaryngologists responded to the survey. Potential cost savings could be seen by patients, payers, and hospital systems with judicious use of surgical pathology, specifically in cases with concurrent signs or symptoms suspicious for malignancy.

4.
OTO Open ; 6(1): 2473974X221086964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387357

RESUMO

Objective: To investigate the popular social media platforms Instagram and Facebook for public posts related to tympanostomy tubes in children, to discern attitudes and perceptions surrounding tympanostomy tubes, and to evaluate the content of social media posts related to tympanostomy tubes. Study Design: Qualitative study. Setting: Instagram and Facebook social media platforms. Methods: Instagram and Facebook were searched for public posts from 2018 and 2019 including the search terms "ear tubes,""ear tube surgery,""tympanostomy," and "myringotomy." Posts were excluded if they were unrelated to pediatric tympanostomy tubes or written in a non-English language. Relevant posts underwent subgroup analysis based on 6 domains: media type, perspective, topic, timeframe, popularity, and overall tone. Results: Of 1862 public social media posts, the majority (78.2%) were made by the patient's parents/caregivers and the rest by physicians (6.0%), hospitals (8.2%), and chiropractors (6.1%), with a few posts by the patients themselves (0.4%). The majority (79.3%) of posts portrayed tympanostomy tubes positively. Most negative posts were made by chiropractors (50.8%) and the patient's parents/caregivers (42.9%). The most common themes of posts were reassurance regarding surgery (74.9%), advertisements (12.5%), apprehension (12.4%), and education (10.3%). Conclusion: Most social media posts were made by parents/caregivers in the perioperative period, and there was a low percentage of educational posts. This information could be used by otolaryngologists to optimize their interactions with patients and parents and to potentially increase physician involvement and educational material related to tympanostomy tubes on social media.

5.
Am J Otolaryngol ; 43(2): 103388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35144105

RESUMO

INTRODUCTION: Social media platforms are constantly evolving and expanding to new populations, exposing their users to various topics and serving as an informal educational resource. Medical ideas and topics are freely discussed online, making understanding of what is present on these platforms of particular importance to the practicing medical professional. In the field of otolaryngology, the public social media portrayal of sinus surgery has not been previously reported. METHODS: Social media posts using keywords related to sinus surgery on Facebook, Instagram, and TikTok were qualitatively analyzed and categorized based on media type, author, subject, timing, depiction, and popularity. RESULTS: The total number of posts included in final analysis was 1798, with a majority stemming from Instagram (68.5%), then Facebook (20.2%) and finally TikTok (11.3%). The most common type of media analyzed was images (69.0%) and patients were more often authors of posts (45.1%) as compared to physicians (34.8%). The subjects of the posts were nearly equally reassurance regarding surgery (41.3%) and educational or informational posts (38.8%) and were most commonly timed in the postoperative period (41.3%). Sinus surgery was depicted in a positive fashion most frequently (56.6%), notably compared against the negative portrayal at 3.2%. Negative posts most commonly cited postoperative pain or bleeding. CONCLUSIONS: Most social media posts analyzed in this multi-platform study depicted sinus surgery in a positive fashion. Patients tended to post in the postoperative or perioperative period, whereas physicians tender to post intraoperative educational posts. Negative posts were most commonly centered around postoperative pain. Cautious interpretation of these results could be used for improving patient care and outreach in the digital age.


Assuntos
Mídias Sociais , Humanos
6.
Ear Nose Throat J ; 101(6): 368-371, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32986491

RESUMO

Pilomatricomas are benign skin tumors often encountered by otolaryngologists but frequently misdiagnosed. Although they can occur at any age, they commonly present in children as a discolored superficial lesion adhered to the overlying skin. Accurate preoperative diagnosis is crucial for appropriate management, which is surgical in most cases. Here, we present bilateral pilomatricomas mimicking features of several other diagnoses in a pediatric patient. The patient was successfully treated with surgical excision. This case presented a unique diagnostic challenge, as the lesions exhibited features of several common diagnoses. In general, surgical management of pilomatricoma is curative, and recurrence is rare.


Assuntos
Doenças do Cabelo , Pilomatrixoma , Neoplasias Cutâneas , Criança , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Doenças do Cabelo/cirurgia , Humanos , Otorrinolaringologistas , Pilomatrixoma/diagnóstico , Pilomatrixoma/patologia , Pilomatrixoma/cirurgia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia
7.
Ear Nose Throat J ; : 1455613211059468, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851765

RESUMO

INTRODUCTION: Despite the presence of clinical practice guidelines for overnight admission of pediatric patients following adenotonsillectomy, variance in practice patterns exists between pediatric otolaryngologists. The purpose of this study is to examine severity of apnea-hypopnea index (AHI) as an independent predictor of postoperative respiratory complications in children undergoing adenotonsillectomy. METHODS: Retrospective chart review of all children undergoing adenotonsillectomy at a large tertiary referral center between January 2015 and December 2019 who underwent preoperative polysomnography and were admitted for overnight observation. Charts were reviewed for total adverse events and respiratory events occurring during admission. RESULTS: Overall, respiratory events were seen in 50.6% of patients with AHI ≥10 and in 39.6% of patients with AHI <10. The overall mean AHI was 19.2, with a mean of 28.1 in the AHI ≥10 subgroup vs 4.6 in the AHI <10 subgroup. There was no statistical correlation or increased risk between an AHI ≥10 and having a pure respiratory event, with a relative risk of 1.19 (.77-1.83, P = .43). There was a statistically significant difference between the mean AHI of those with any adverse event and those without (21.6 vs 13.4, P = .008). There is additionally an increased risk of any event with an AHI over 10, with a relative risk of 1.51 (1.22-1.88, P < .0001). CONCLUSION: Preoperative AHI of 10 events per hour was not a predictor of postoperative respiratory complications. However, there was a trend for those with a higher AHI requiring additional supportive measures or a prolonged stay. Practitioners should always use their best judgment in deciding whether a child warrants postoperative admission following adenotonsillectomy.

10.
Int J Pediatr Otorhinolaryngol ; 122: 40-43, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951971

RESUMO

OBJECTIVE: In 2013 the American Academy of Otolaryngology published tympanostomy tube guidelines for children; Action Statement 6 recommends against tube placement without middle ear effusion (MEE) at time of assessment. To date, little research has directly evaluated this recommendation in reducing the need for ear tubes. We evaluated the effectiveness of this recommendation and potential risk factors that influence the success of watchful waiting. METHODS: Retrospective chart review collecting demographics, daycare status, smoking exposure, and time of year of visit. Children aged 6 months to 12 years without MEE on presentation, but with 3 or more episodes of acute otitis media (AOM) in 6 months or 4 or more episodes in 12 months, were assigned to watchful waiting (WW) treatment. These patients were followed every 4 months or returned sooner with additional infections. Any continued AOM, or MEE on follow up leading to tube placement, defined WW failure. RESULTS: 123 patients met criteria, with 81 still in WW to date (66% success rate). 42 children failed WW and received tympanostomy tubes (34% failure rate). There were no statistically significant associations between age, race, gender, smoking exposure, daycare, or month of presentation between children who failed WW compared to children receiving tubes. CONCLUSIONS: Tympanostomy tube guidelines mitigate unnecessary tube placement in a majority of children with recurrent AOM without MEE. To our knowledge, this is the first study supporting the 2013 recommendations, with a 66% success rate. Additionally, no significant associations between modifying risk factors in those who failed watchful waiting were identified.


Assuntos
Ventilação da Orelha Média/estatística & dados numéricos , Otite Média/terapia , Procedimentos Desnecessários , Conduta Expectante/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Otite Média com Derrame/cirurgia , Guias de Prática Clínica como Assunto , Recidiva , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
11.
Breast Cancer Res ; 17: 112, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26286584

RESUMO

INTRODUCTION: The steady increase in the incidence of obesity among adults has been paralleled with higher levels of obesity-associated breast cancer. While recent studies have suggested that adipose stromal/stem cells (ASCs) isolated from obese women enhance tumorigenicity, the mechanism(s) by which this occurs remains undefined. Evidence suggests that increased adiposity results in increased leptin secretion from adipose tissue, which has been shown to increased cancer cell proliferation. Previously, our group demonstrated that ASCs isolated from obese women (obASCs) also express higher levels of leptin relative to ASCs isolated from lean women (lnASCs) and that this obASC-derived leptin may account for enhanced breast cancer cell growth. The current study investigates the impact of inhibiting leptin expression in lnASCs and obASCs on breast cancer cell (BCC) growth and progression. METHODS: Estrogen receptor positive (ER+) BCCs were co-cultured with leptin shRNA lnASCs or leptin shRNA obASCs and changes in the proliferation, migration, invasion, and gene expression of BCCs were investigated. To assess the direct impact of leptin inhibition in obASCs on BCC proliferation, MCF7 cells were injected alone or mixed with control shRNA obASCs or leptin shRNA obASCs into SCID/beige mice. RESULTS: ER+ BCCs were responsive to obASCs during direct co-culture, whereas lnASCs were unable to increase ER(+) BCC growth. shRNA silencing of leptin in obASCs negated the enhanced proliferative effects of obASC on BCCs following direct co-culture. BCCs co-cultured with obASCs demonstrated enhanced expression of epithelial-to-mesenchymal transition (EMT) and metastasis genes (SERPINE1, MMP-2, and IL-6), while BCCs co-cultured with leptin shRNA obASCs did not display similar levels of gene induction. Knockdown of leptin significantly reduced tumor volume and decreased the number of metastatic lesions to the lung and liver. These results correlated with reduced expression of both SERPINE1 and MMP-2 in tumors formed with MCF7 cells mixed with leptin shRNA obASCs, when compared to tumors formed with MCF7 cells mixed with control shRNA obASCs. CONCLUSION: This study provides mechanistic insight as to how obesity enhances the proliferation and metastasis of breast cancer cells; specifically, obASC-derived leptin contributes to the aggressiveness of breast cancer in obese women.


Assuntos
Tecido Adiposo/metabolismo , Neoplasias da Mama/metabolismo , Proliferação de Células/genética , Leptina/metabolismo , Metástase Neoplásica/genética , Células-Tronco/metabolismo , Células Estromais/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Adiposidade/genética , Animais , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Técnicas de Cocultura/métodos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Células MCF-7 , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos SCID , Metástase Neoplásica/patologia , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , RNA Interferente Pequeno/genética , Receptores de Estrogênio/genética , Células-Tronco/patologia , Células Estromais/patologia
12.
JAMA Otolaryngol Head Neck Surg ; 141(9): 804-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26313895

RESUMO

IMPORTANCE: Specific temporal goals for treatment of head and neck cancer (HNC) are common in Europe but not in the United States. We implemented a patient-centric navigation model with an aspirational goal that all patients will receive treatment recommendations within 2 weeks of presentation as a means to improve outcomes in our patients with HNC. OBJECTIVE: To assess the temporal impact of using an aspirational goal in a patient-centric navigation system on the time from presentation to formulation of treatment planning for patients with HNC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 100 consecutive patients treated for squamous cell carcinoma of the head and neck at a tertiary referral center between 2011 and 2014. Patients were assessed to determine the efficiency of a patient-centric navigational model in delivering cancer treatment recommendations. This model was designed with an aspirational goal of providing treatment recommendations within a 2-week period. EXPOSURE: Starting in 2011, patient-centric navigation model including the assignment of a nurse who acts as a patient navigator. MAIN OUTCOMES AND MEASURES: The time interval between presentation to clinic and definitive treatment recommendations, as well as factors associated with delay. RESULTS: Of the 93 patients who met inclusion requirements, most were white (81 [87%]) males (74 [80%]) with a mean (SD) age of 63.4 (10.8) years insured by Medicare or Medicaid (64 [69%]). Forty-seven (51%) received treatment recommendations within the 2-week period, with median and mode values of 15 and 14 days, respectively. The mean (SD) interval was 18.8 (18.6) days. Outliers included 2 patients with synchronous lung nodules (72 and 85 days) and 2 patients with psychosocial barriers (107 and 86 days). There were no significant differences seen for the mean (SD) time interval with respect to patient race (blacks, 17.6 [15.7] vs whites, 22.5 [30.0]; P = .20), sex (males, 18.3 [18.1] vs females, 20.4 [19.7]; P = .13), insurance status (insured, 16.3 [10.2] vs uninsured, 19.8 [21.0]; P = .24), and stage at presentation (stage I, 14.4 [17.0] vs stage II, 11.0 [5.3] vs stage III, 14.7 [8.6] vs stage IV, 21.2 [20.2]; P = .40). CONCLUSIONS AND RELEVANCE: The goal of treatment recommendations for HNC within 2 weeks was shown to be reasonable and attainable. Further research should address the delays encountered by patients with psychosocial barriers and those with synchronous lung nodules.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Modelos Organizacionais , Neoplasias Otorrinolaringológicas/cirurgia , Navegação de Pacientes/organização & administração , Idoso , Carcinoma de Células Escamosas/patologia , Eficiência Organizacional , Feminino , Implementação de Plano de Saúde/organização & administração , Hospitais Universitários , Humanos , Louisiana , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Fluxo de Trabalho
13.
J Mol Endocrinol ; 53(3): 345-53, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25143472

RESUMO

Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM-10 µM). The extent of adipogenic differentiation in the ASCs was assessed by staining with Oil Red O to visualize adipogenic differentiation and then quantified by extraction and optical density measurement of the retained dye. BPA significantly enhanced adipogenesis at a concentration of 1 µM after 21 days of culture. Additionally, we found that BPA increased transcription of the estrogen receptor (ER (ESR1)) and that treatment with the ER antagonist ICI 182 780, blocked the effects of BPA, indicating that BPA may act via an ER-mediated pathway. The results of molecular analyses indicated that the expression of the adipogenesis-associated genes dual leucine zipper-bearing kinase (DLK (MAP3K12)), IGF1, CCAAT/enhancer-binding protein alpha (C/EBPα (CEBPA)), peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), and lipoprotein lipase (LPL) was temporally accelerated and increased by BPA. In summary, these results indicate that BPA significantly enhances adipogenesis in ASCs through an ER-mediated pathway at physiologically relevant concentrations.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Células-Tronco Adultas/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Fenóis/farmacologia , Células Estromais/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Adulto , Células-Tronco Adultas/fisiologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Pessoa de Meia-Idade , Células Estromais/fisiologia , Regulação para Cima/efeitos dos fármacos
14.
Stem Cell Res Ther ; 5(4): 105, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-25168698

RESUMO

INTRODUCTION: Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein and daidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs). Herein, the effects of daidzein analogs on the osteogenic differentiation efficiency of human BMSC and adipose-derived stromal/stem cells (ASC) were explored. METHODS: BMSCs and ASCs underwent osteogenic differentiation in the presence of vehicle, 17ß-estradiol (E2), phytoestrogens, or daidzein analogs. Cells were stained for alkaline phosphatase (ALP) enzymatic activity, calcium deposition by alizarin red s, and phosphate mineralization by silver nitrate. Gene expression analysis was conducted on cells treated with daidzein analogs. RESULTS: Cells treated with E2, daidzein, or genistein increased calcium deposition by 1.6-, 1.5-, and 1.4-fold, respectively, relative to vehicle-treated BMSCs and 1.6-, 1.7-, and 1.4-fold relative to vehicle-treated ASCs, respectively. BMSCs treated with daidzein analog 2c, 2g, and 2l demonstrated a 1.6-, 1.6-, and 1.9-fold increase in calcium deposition relative to vehicle-treated BMSCs, respectively, while ASCs treated with daidzein analog 2c, 2g, or 2l demonstrated a 1.7-, 2.0-, and 2.2-fold increase in calcium deposition relative to vehicle-treated ASCs, respectively. Additional analysis with BMSCs and ASCs was conducted in the more efficient compounds: 2g and 2l. ALP activity and phosphate mineralization was increased in 2g- and 2l-treated cells. The analysis of lineage specific gene expression demonstrated increased expression of key osteogenic genes (RUNX2, c-FOS, SPARC, DLX5, SPP1, COL1A1, IGF1, SOST, and DMP1) and earlier induction of these lineage specific genes, following treatment with 2g or 2l, relative to vehicle-treated cells. Estrogen receptor (ER) inhibitor studies demonstrated that ER antagonist fulvestrant inhibited the osteogenic differentiation of 2g in BMSCs and ASCs, while fulvestrant only attenuated the effects of 2l, suggesting that 2l acts by both ER dependent and independent pathways. CONCLUSIONS: These studies provide support for exploring the therapeutic efficacy of daidzein derivatives for the treatment of osteoporosis. Furthermore, the patterns of gene induction differed following treatment with each daidzein analog, suggesting that these daidzein analogs activate distinct ER and non-ER pathways to induce differentiation in BMSCs and ASCs.


Assuntos
Células-Tronco Adultas/fisiologia , Conservadores da Densidade Óssea/farmacologia , Isoflavonas/farmacologia , Células-Tronco Mesenquimais/fisiologia , Receptores de Estrogênio/fisiologia , Células-Tronco Adultas/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Células da Medula Óssea/fisiologia , Diferenciação Celular , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Fulvestranto , Humanos , Concentração Inibidora 50 , Osteogênese , Osteoporose/tratamento farmacológico , Fitoestrógenos/farmacologia
15.
J Cardiovasc Pharmacol ; 49(6): 362-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17577100

RESUMO

Angiotensin II (Ang II) activates p38 mitogen-activated protein kinase (p38 MAPK) and increases reactive oxygen species (ROS), but the nature of the relationship in vivo is not fully understood. We assess the effect of SB239063AN, a highly selective, orally active, p38 MAPK inhibitor, on Ang II-dependent hypertension, target-organ damage and ROS production. Sprague-Dawley rats and MAPKAP kinase-2 knockout mice were infused with Ang II. Ang II infusion increased the levels of phosphorylated p38 MAPK in the heart and aorta. Production of superoxide anion and expression of NAD(P)H oxidase subunit gp91 in the aorta were increased 4- and 5-fold, respectively. In addition, Ang II infusion led to endothelial dysfunction, progressive and sustained hypertension, and cardiac hypertrophy. Treatment with SB239063AN (800 ppm in the diet) significantly attenuated the levels of phosphorylated p38 MAPK in the heart and aorta, reduced superoxide anion generation by 57% (P < 0.01), markedly suppressed gp91 mRNA expression, prevented endothelial dysfunction, and blunted both the hypertension and cardiac hypertrophy. Ang II-dependent hypertension was also significantly attenuated in MAPKAP kinase-2 knockout mice. The results suggest that Ang II induced hypertension, organ damage, and ROS production are possibly mediated by p38 MAPK and inhibition of p38 MAPK may offer a therapeutic approach for cardiovascular disease.


Assuntos
Angiotensina II/efeitos adversos , Inibidores Enzimáticos , Hipertensão/tratamento farmacológico , Imidazóis , Pirimidinas , Superóxidos/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/enzimologia , Aorta Abdominal/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/enzimologia , Artérias Carótidas/metabolismo , Ecocardiografia , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Hipertensão/induzido quimicamente , Hipertensão/enzimologia , Hipertensão/metabolismo , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Miocárdio/enzimologia , Miocárdio/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese
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