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1.
OTO Open ; 8(2): e164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938507

RESUMO

Objective: Advances in deep learning and artificial intelligence (AI) have led to the emergence of large language models (LLM) like ChatGPT from OpenAI. The study aimed to evaluate the performance of ChatGPT 3.5 and GPT4 on Otolaryngology (Rhinology) Standardized Board Examination questions in comparison to Otolaryngology residents. Methods: This study selected all 127 rhinology standardized questions from www.boardvitals.com, a commonly used study tool by otolaryngology residents preparing for board exams. Ninety-three text-based questions were administered to ChatGPT 3.5 and GPT4, and their answers were compared with the average results of the question bank (used primarily by otolaryngology residents). Thirty-four image-based questions were provided to GPT4 and underwent the same analysis. Based on the findings of an earlier study, a pass-fail cutoff was set at the 10th percentile. Results: On text-based questions, ChatGPT 3.5 answered correctly 45.2% of the time (8th percentile) (P = .0001), while GPT4 achieved 86.0% (66th percentile) (P = .001). GPT4 answered image-based questions correctly 64.7% of the time. Projections suggest that ChatGPT 3.5 might not pass the American Board of Otolaryngology Written Question Exam (ABOto WQE), whereas GPT4 stands a strong chance of passing. Discussion: The older LLM, ChatGPT 3.5, is unlikely to pass the ABOto WQE. However, the advanced GPT4 model exhibits a much higher likelihood of success. This rapid progression in AI indicates its potential future role in otolaryngology education. Implications for Practice: As AI technology rapidly advances, it may be that AI-assisted medical education, diagnosis, and treatment planning become commonplace in the medical and surgical landscape. Level of Evidence: Level 5.

2.
J Clin Sleep Med ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38935051

RESUMO

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) therapy has historically had strict eligibility requirements including a body mass index (BMI) < 32 kg/m2. However, recent Food and Drug Administration approval expanded indications to a BMI < 40 kg/m2. There is a wide variability in body fat distribution. This study sought to determine if neck circumference is a better surrogate predictive variable for HGNS outcomes than BMI. METHODS: A retrospective chart review was conducted at a tertiary care center on adults who underwent HGNS implantation by a single surgeon from March 2017 to October 2021. Baseline demographic data including neck circumference, diagnostic sleep studies and post-implantation HGNS titration studies were collected. Linear regression and Spearman's Correlation Coefficient (SCC) analysis were utilized to compare neck circumference (NC), percentage of predicted neck circumference (PPNC) and BMI with the apnea-hypopnea index at effective voltage (AHI-v). RESULTS: This study included 43 patients who were middle aged (61.1 years), predominantly male (76.7%), with severe obstructive sleep apnea (median AHI 35) and mean neck circumference of 15.3 inches. Utilizing the NC and PPNC, positive correlations with AHI-v were observed (p = 0.0033, SCC = .438, and p = 0.0029, SCC = .444). While controlling for BMI, a 1-inch increase in neck circumference was associated with a 35% increase in AHI-v (p = 0.0411). CONCLUSIONS: A larger neck circumference was independently associated with worse HGNS outcomes. Further research is needed to support and confirm these findings, particularly across sexes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38751109

RESUMO

OBJECTIVE: The recommended readability of health education materials is at the sixth-grade level. Artificial intelligence (AI) large language models such as the newly released ChatGPT4 might facilitate the conversion of patient-education materials at scale. We sought to ascertain whether online otolaryngology education materials meet recommended reading levels and whether ChatGPT4 could rewrite these materials to the sixth-grade level. We also wished to ensure that converted materials were accurate and retained sufficient content. METHODS: Seventy-one articles from patient educational materials published online by the American Academy of Otolaryngology-Head and Neck Surgery were selected. Articles were entered into ChatGPT4 with the prompt "translate this text to a sixth-grade reading level." Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL) were determined for each article before and after AI conversion. Each article and conversion were reviewed for factual inaccuracies, and each conversion was reviewed for content retention. RESULTS: The 71 articles had an initial average FKGL of 11.03 and FRES of 46.79. After conversion by ChatGPT4, the average FKGL across all articles was 5.80 and FRES was 77.27. Converted materials provided enough detail for patient education with no factual errors. DISCUSSION: We found that ChatGPT4 improved the reading accessibility of otolaryngology online patient education materials to recommended levels quickly and effectively. IMPLICATIONS FOR PRACTICE: Physicians can determine whether their patient education materials exceed current recommended reading levels by using widely available measurement tools, and then apply AI dialogue platforms to modify materials to more accessible levels as needed. LEVEL OF EVIDENCE: Level 5.

4.
Laryngoscope ; 134(5): 2464-2470, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37905744

RESUMO

OBJECTIVES: Recent evidence suggests that environmental factors impact craniofacial development. Specifically, the height and width of the maxilla may impact the degree of septal deviation. We sought to determine the relationship between transverse maxillary deficiency and severity of septal deviation. METHODS: A prospective cohort of adult sleep surgery patients were evaluated by standardized CT imaging. Primary outcomes evaluated the relationship of a narrow, high-arched palate (the palatal height to width ratio) with the degree of septal deviation at the level of the 1st premolar and 1st molar. Secondary outcome evaluated the relationship of the palatal height-to-width ratio and nasal obstruction. Both adjusted and unadjusted linear regression were performed, including correction for multiple hypothesis testing. RESULTS: Ninety-three patients were included. On average, the cohort was middle aged (54.7 ± 12.7 years), obese (BMI 30.1 ± 4.5 kg/m2), predominantly male (74.2%), White (73.1%), and with severe obstructive sleep apnea (OSA) (AHI 30.0 ± 18.7 events/h). A moderate correlation was observed between both the relative and absolute inter-premolar palatal height and the degree of septal deviation at the inter-molar region. No significant correlation was observed between palatal dimensions and NOSE score. CONCLUSION: This study found that transverse maxillary deficiency is moderately associated with greater degree of septal deviation among a sample of OSA patients. This contributes to the concept that craniofacial development impacts the nasal airway, promoting a comprehensive evaluation of both endonasal and extranasal structures. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2464-2470, 2024.


Assuntos
Obstrução Nasal , Apneia Obstrutiva do Sono , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Estudos Prospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Nariz , Palato , Obstrução Nasal/etiologia
5.
J Clin Sleep Med ; 20(1): 93-99, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707285

RESUMO

STUDY OBJECTIVES: Drug-induced sleep endoscopy with positive airway pressure evaluates the collapsibility of the upper airway. It is currently unknown whether body position affects this assessment. We sought to determine whether the collapsibility of the airway may change with head of bed elevation. METHODS: A prospective, consecutive cohort study was performed by 2 sleep surgeons at a tertiary care center. Inclusion criteria included adults 18 years of age and older with obstructive sleep apnea who were intolerant to continuous positive airway pressure therapy. Patients underwent drug-induced sleep endoscopy with positive airway pressure to evaluate them for alternative treatment options. Patients were evaluated in supine position with the head of bed both level and elevated to 30°. The airway was evaluated using the standardized VOTE scoring system in both positions. RESULTS: The 61 patients included in the study were predominantly male (70.5%), middle-aged (51.2 years), and obese (body mass index, 30.2 kg/m2) with moderate-to-severe obstructive sleep apnea (apnea-hypopnea index, 34.1 events/h). The cohort consisted of predominantly positional obstructive sleep apnea (mean supine apnea-hypopnea index 48.7 events/h, nonsupine apnea-hypopnea index 20.8 events/h). All 4 sites of the upper airway demonstrated a significant decrease in airway opening pressures with the head of bed elevated compared to level (P < .01 for all sites). There was no significant difference in VOTE scoring between level and upright positions. CONCLUSIONS: Patients with the head of bed elevated to 30° have a significantly lower degree of airway collapsibility compared to patients in the level position but no significant change in VOTE scoring was observed. CITATION: Owen GS, Talati VM, Zhang Y, LoSavio PS, Hutz MJ. The effect of head of bed elevation on upper airway collapsibility during drug-induced sleep endoscopy. J Clin Sleep Med. 2024;20(1):93-99.


Assuntos
Apneia Obstrutiva do Sono , Sono , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Adolescente , Feminino , Polissonografia , Estudos de Coortes , Estudos Prospectivos , Endoscopia
6.
Laryngoscope ; 134(4): 1970-1977, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37772955

RESUMO

OBJECTIVE: Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to assess the feasibility, preliminary outcomes, and safety of posterior palatal expansion via subnasal endoscopy (2PENN), a modified SARPE procedure, aimed at achieving anterior and posterior maxillary expansion. METHODS: This prospective case series included consecutive adult patients with findings of transverse maxillary deficiency that underwent the 2PENN procedure from 4/2021 to 4/2022. Patients completed pre- and post-operative clinical evaluations, Nasal Obstruction and Septoplasty Effectiveness (NOSE) questionnaires, and computed tomography (CT), with measures including expansion at the level of the posterior nasal spine (PNS), first maxillary inter-molar distance (IMD), and anterior nasal spine (ANS). RESULTS: The cohort (N = 20) was middle-aged (39 ± 11 years), predominantly male (80%), and overweight (BMI 28 ± 4 kg/m2 ). The majority (85%) of patients had sleep breathing issues, of which 10 (59%) had polysomnography-confirmed obstructive sleep apnea (OSA). Full anterior-posterior separation of the mid-palatal suture line was evident on all post-operative CT scans, with mean expansion at the PNS of 3.6 ± 1.3 mm, IMD of 6.1 ± 1.6 mm and ANS of 7.0 ± 1.6 mm (p < 0.001). Following surgery, mean NOSE scores improved from 57 ± 23 to 14 ± 13 (p < 0.001). One patient required maxillary antrostomy for post-operative sinusitis. CONCLUSION: 2PENN is an effective and safe technique for achieving both anterior and posterior maxillary expansion in patients with transverse maxillary deficiency. Further study is warranted to better understand the effect of 2PENN in patients with OSA, particularly as it relates to improving pharyngeal patency. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1970-1977, 2024.


Assuntos
Micrognatismo , Obstrução Nasal , Apneia Obstrutiva do Sono , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Técnica de Expansão Palatina , Projetos Piloto , Obstrução Nasal/diagnóstico por imagem , Obstrução Nasal/etiologia , Obstrução Nasal/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Endoscopia Gastrointestinal , Maxila/cirurgia
7.
Laryngoscope ; 133(10): 2821-2822, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37036098

RESUMO

Infection and extrusion of hardware are known complications of hypoglossal nerve stimulation surgery. We present a unique case of an extruded hardware lead successfully managed with reimplantation without need for explantation and new device placement. The topic will be discussed in context of the body of literature related to extruded medical device management. Laryngoscope, 133:2821-2822, 2023.


Assuntos
Terapia por Estimulação Elétrica , Nervo Hipoglosso , Humanos , Nervo Hipoglosso/cirurgia , Reimplante , Remoção de Dispositivo , Reoperação
8.
Laryngoscope ; 132(10): 2076-2077, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35815734

RESUMO

Drug-induced sleep endoscopy with positive airway pressure (DISE-PAP) is a new technique that allows for both the visualization of upper airway collapse as well as to evaluate the degree of airway collapsibility. This DISE-PAP protocol provides an affordable and clinically efficient manner in which to immediately implement this technique in clinical practice. Laryngoscope, 132:2076-2077, 2022.


Assuntos
Apneia Obstrutiva do Sono , Endoscopia/métodos , Humanos , Nariz , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia
9.
Otolaryngol Head Neck Surg ; 166(1): 60-67, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33878987

RESUMO

OBJECTIVE: We performed a systematic review and meta-analysis of deep lobe parotid tumors to evaluate their unique characteristics. DATA SOURCES: PubMed/Medline, Embase, Web of Sciences, and Cochrane Library databases were queried for relevant literature. REVIEW METHODS: Studies were individually assessed by 2 independent reviewers. Risk of bias was assessed with the Cochrane bias tool, GRADE criteria, and MINORS criteria. Results were reported according to the PRISMA guidelines. Statistical analysis was performed by comparing rates of malignancy between deep and superficial lobe tumors. RESULTS: In total, 8 studies including 379 deep lobe parotid tumors met inclusion criteria. Mean age at diagnosis was 44.9 years. Computed tomography scan was the most common imaging modality. Preoperative diagnostic fine-needle aspiration was utilized in 39.4% of patients and demonstrated high sensitivity for malignant disease. The most common approach was subtotal parotidectomy with facial nerve preservation (58.9%). The rate of malignancy was 26.6%, which was significantly higher than that of the superficial lobe tumors in this study (risk ratio, 1.25; 95% CI, 1.01-1.56). The rate of temporary postoperative facial nerve weakness between deep and superficial lobe tumors was 32.5% and 11.7%, respectively. CONCLUSION: Deep lobe parotid tumors had a 26.6% rate of malignancy. On meta-analysis, deep lobe tumors appeared to have higher rates of malignancy than superficial lobe tumors. Surgical excision of deep lobe tumors showed increased rates of temporary facial nerve paresis as compared with superficial lobe tumors. Computed tomography scan was the most common imaging modality. There were limited data regarding the utility of fine-needle aspiration.


Assuntos
Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos , Neoplasias Parotídeas/diagnóstico por imagem , Adulto Jovem
10.
Front Neurol ; 12: 723024, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956038

RESUMO

Nerve injury resulting in muscle paralysis from trauma or surgery is a major medical problem. Repair of such injuries with existing nerve grafting and reconstructive techniques often results in less than optimal outcomes. After previously demonstrating significant return of function using muscle-nerve-muscle (MNM) grafting in a rat facial nerve model, this study compares a variant of the technique, muscle-nerve-nerve (MNN) neurotization to MNM and interposition (IP) nerve grafting. Thirty male rats were randomized into four groups (1) control with no intervention, (2) repair with IP grafts, (3) MNM grafts and (4) MNN grafts. All groups had the buccal and marginal mandibular branches of the right facial nerve resected. Return of vibrissae movement, orientation, and snout symmetry was measured over 16 weeks. Functional recovery and muscle atrophy were assessed and quantified. All interventions resulted in significant improvement in vibrissae movement and orientation as compared to the control group (p < 0.05). The MNM and MNN groups had significantly less time to forward vibrissae movement as compared to controls (p < 0.05), and a large number of animals in the MNN group had coordinated vibrissae movement at 16 weeks. MNN and IP grafts retained significantly more muscle mass as compared to control (p < 0.05). Thus, MNN grafting is a promising adjuvant or alternative technique for reanimation for patients with unilateral peripheral nerve injury who are not candidates for primary neurorrhaphy.

11.
Laryngoscope ; 131(1): E248-E249, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057112

RESUMO

A novel technique for the diagnosis and management of middle ear myoclonus is described. A patient with middle ear myoclonus underwent a trans-canal microscopic middle ear exploration with injection of botulinum toxin into the stapedius and tensor tympani muscles. Postoperatively, the patient noted complete resolution of symptoms. This is the first report of the use of botulinum toxin directly applied to the middle ear musculature via a trans-canal approach for the management of middle ear myoclonus. This approach is both a useful diagnostic and therapeutic tool that allows for temporary muscle paralysis prior to offering definitive surgical management. Laryngoscope, 131:E248-E249, 2021.


Assuntos
Orelha Média , Mioclonia , Inibidores da Liberação da Acetilcolina/administração & dosagem , Adulto , Toxinas Botulínicas/administração & dosagem , Humanos , Injeção Intratimpânica , Masculino , Mioclonia/diagnóstico , Mioclonia/tratamento farmacológico , Tensor de Tímpano
12.
WMJ ; 119(3): 205-210, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33091292

RESUMO

INTRODUCTION: While most patients note a complete resolution of facial paralysis in Bell's Palsy, up to 30% will have persistent facial weakness and develop synkinesis. All branches of the facial nerve are at risk for developing synkinesis, but stapedial synkinesis has rarely been reported in the literature. CASE PRESENTATION: A 45-year-old man presented with sudden onset, complete right facial paralysis. One-and-a-half years later, he had persistent facial weakness and synkinesis. He noted persistent right aural fullness and hearing loss. Audiometry demonstrated facial-stapedial synkinesis. DISCUSSION: The patient was diagnosed with stapedial synkinesis based on audiometric findings by comparing his hearing at rest and with sustained facial mimetic movement. A literature review revealed 21 reported cases of this disorder. CONCLUSIONS: Facial-stapedial synkinesis is an underdiagnosed phenomenon for patients recovering from idiopathic facial palsy. Patients who develop facial synkinesis also may have a component of stapedial synkinesis and should be referred to an otolaryngologist if they complain of any otologic symptoms, such as unilateral hearing loss or tinnitus. Definitive management involves surgical transection of the stapedial tendon.


Assuntos
Paralisia de Bell , Paralisia Facial , Sincinesia , Humanos , Masculino , Pessoa de Meia-Idade , Sincinesia/diagnóstico , Sincinesia/etiologia
13.
Laryngoscope ; 130(12): E958-E962, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32109324

RESUMO

OBJECTIVE: To determine if a modified tissue-preserving palatopharyngoplasty could convert retropalatal concentric collapse to anteroposterior or lateral patterns of collapse on drug-induced sleep endoscopy (DISE) in patients who are not candidates for upper airway stimulation due to complete circumferential collapse at the velum. METHODS: A prospective, nonconsecutive, single-blinded cohort study was performed by two sleep surgeons at a tertiary care center from 2015 to 2018. Inclusion criteria included adults > 18 years of age with a diagnosis of obstructive sleep apnea with an Apnea-Hypopnea Index (AHI) > 15, a body mass index (BMI) < 32, and < 25% central apneas on polysomnography. Twelve patients with complete circumferential collapse underwent a modified palatopharyngoplasty. Postoperatively, a repeat sleep study was performed. A repeat DISE was recommended for those with incomplete surgical response (clinically and/or AHI). RESULTS: Twelve patients with complete circumferential collapse were eligible for the study. Mean BMI was 30.5. Mean preoperative AHI was 54.0 events per hour. Following a modified palatopharyngoplasty, the mean AHI was reduced to 33.1 events per hour, and 100% (12 of 12) of the patients converted from a pattern of complete circumferential collapse to either no collapse at the level of the velum (3) or an anteroposterior pattern of collapse (9). CONCLUSION: We demonstrate that a modified palatopharyngoplasty can successfully convert collapse patterns in patients with complete circumferential collapse. Further studies are required to determine the outcome of these patients following upper airway stimulation implantation. LEVEL OF EVIDENCE: 1B Laryngoscope, 2020.


Assuntos
Faringe/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Úvula/cirurgia , Adulto , Idoso , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Apneia Obstrutiva do Sono/terapia
14.
Otolaryngol Head Neck Surg ; 162(4): 458-468, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32093508

RESUMO

OBJECTIVES: To perform an evidence-based review evaluating presenting symptoms, imaging, and management for primary paragangliomas of the facial canal (PPFCs). DATA SOURCES: PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science. REVIEW METHODS: Studies were assessed for quality of evidence and bias with the Cochrane bias tool, GRADE, and MINORS criteria. Demographic data, imaging modalities, management strategies, and status at last follow-up were obtained. RESULTS: Sixteen studies met inclusion criteria. In total, 21 patients with PPFCs were identified, 19 of which were histologically confirmed. Most common presenting symptoms included unilateral facial nerve dysfunction (n = 14, 73.7%) and pulsatile tinnitus (n = 8, 42.1%). Mean time from reported onset of facial dysfunction was 17.8 months. Computed tomography findings included an expanded descending facial nerve canal (n = 13, 76.5%). All cases with magnetic resonance imaging reported enhancement with contrast. Of the 18 patients who had surgery, 16 (88.9%) underwent full tumor resection while 1 (5.6%) had partial tumor debulking with adjuvant radiotherapy. Overall improvement in facial weakness was documented in 5 of 9 patients (55.6%) with initial facial nerve dysfunction and >6-month follow-up. No evidence of tumor recurrence was reported. CONCLUSIONS: PPFCs are extraordinarily rare vascular neoplasms of the temporal bone. Early imaging with both computed tomography and magnetic resonance imaging is essential for narrowing the differential diagnosis, assessing the extent of tumor invasion, and accurate surgical planning. Surgical tumor resection with subsequent facial nerve reconstruction is recommended for patients with facial nerve dysfunction, while tumor biopsy or debulking may be indicated when normal facial movement in present.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Paraganglioma/diagnóstico , Paraganglioma/terapia , Osso Temporal , Medicina Baseada em Evidências , Humanos
15.
Curr Neurol Neurosci Rep ; 18(3): 11, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29445883

RESUMO

PURPOSE OF REVIEW: The aim of this study is to discuss the symptoms, diagnosis, and management of the neurologic complications of acute and chronic otitis media. RECENT FINDINGS: Antibiotic therapy has greatly reduced the frequency of complications of otitis media. However, it is of vital importance to remain aware of the possible development of neurologic complications. There is a trend toward less severe presenting symptoms including otorrhea, headache, nausea, and fever, with altered mental status and focal neurologic deficits presenting later. In order to reduce morbidity, early deployment of a multidisciplinary approach with prompt imaging and laboratory studies is imperative to guide appropriate management. Complications of acute and chronic otitis media may present with neurologic signs and symptoms. It is important to recognize the possible otitic origin of such complications to ensure proper management and to decrease overall morbidity and mortality.


Assuntos
Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Otite Média/complicações , Otite Média/diagnóstico , Doença Aguda , Antibacterianos/uso terapêutico , Criança , Doença Crônica , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/etiologia , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Perda Auditiva/diagnóstico , Perda Auditiva/tratamento farmacológico , Perda Auditiva/etiologia , Humanos , Doenças do Sistema Nervoso/tratamento farmacológico , Otite Média/tratamento farmacológico
16.
Pharmacol Biochem Behav ; 117: 17-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24316201

RESUMO

Studies in male rodents have shown that stress-induced increases in circulating corticosterone are increased by both CB1 receptor (CB1R) antagonist treatment and genetic deletion. The purposes of the current study were to determine whether female mice respond in the same manner as males, and whether indirect CB1R agonists accelerate the return of corticosterone to baseline. In agreement with earlier studies, CB1R null and rimonabant-treated male mice had significantly increased circulating corticosterone 30 min following the end of a restraint episode compared to wild type and vehicle-treated, respectively. Females treated with rimonabant had significantly higher circulating corticosterone compared to vehicle. However, corticosterone concentrations were not different between CB1R null and wild type females at 30 min recovery, although CB1R null mice had higher corticosterone concentrations at 90 min of recovery. Female CB1R null mice exhibited greater serum binding capacity for corticosterone than wild type. The monoacylglycerol lipase inhibitor, JZL184, attenuated corticosterone concentrations at restraint offset in male, and at 30 min recovery in female mice compared to vehicle. Male mice treated with JZL184 exhibited greater concentrations of circulating corticosterone at 120 min recovery, even in the absence of restraint. JZL184 had no effect on corticosterone concentrations in CB1R null mice. The fatty acid amide hydrolase inhibitor, URB597, did not affect corticosterone responses to restraint in male or female, wild type or CB1R null mice. These data suggest that 2-arachidonoylglycerol is the primary endocannabinoid involved in CB1R regulation of the recovery of the HPA axis from restraint stress. These data support a role for endocannabinoid-CB1R signaling in the regulation of the corticosterone response to restraint stress and suggest that female mice with life-long loss of the CB1R undergo compensatory changes that minimize the impact of loss of endocannabinoid signaling on circulating corticosterone.


Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Endocanabinoides/metabolismo , Sistema Hipotálamo-Hipofisário , Piperidinas/farmacologia , Sistema Hipófise-Suprarrenal , Pirazóis/farmacologia , Transdução de Sinais , Estresse Fisiológico , Córtex Suprarrenal/fisiopatologia , Animais , Corticosterona/sangue , Endocanabinoides/agonistas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Receptor CB1 de Canabinoide/genética , Rimonabanto
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