RESUMEN
This study aimed to investigate the clinical, radiological, and pathological characteristics of pathologies involving the buccal fat pad (BFP) and to explore the treatment protocols. The cases of 109 patients with primary pathologies involving the BFP (pBFP) diagnosed between January 2013 and September 2021 were assessed. The patients' clinical presentations and radiological and histopathological findings were analysed retrospectively, and their treatment outcomes were evaluated. The 109 pBFP were categorized as benign tumours (n = 17), malignant tumours (n = 29), vascular malformations (n = 38), and inflammatory masses (n = 25). Of the 17 benign tumours, seven were lipomas, five were pleomorphic adenomas, three were solitary fibrous tumours, and two were other tumours. The 29 malignant tumours included five adenoid cystic carcinomas, six mucoepidermoid carcinomas, three synovial sarcomas, and 15 other tumours. Of the 38 vascular malformations, 37 were venous and one was arteriovenous. Regarding the inflammatory masses, the lesions appeared after cosmetic facial botulinum toxin injection in 13 cases and after other cosmetic facial procedures in five. The upper body of the BFP was the most frequently involved site (79/109), while other frequently involved sites were the lower body (67/109) and the masseteric (41/109), temporal (32/109), and pterygopalatine (30/109) extensions.
Asunto(s)
Adenoma Pleomórfico , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Malformaciones Vasculares , Humanos , Neoplasias de las Glándulas Salivales/terapia , Neoplasias de las Glándulas Salivales/patología , Estudios Retrospectivos , Adenoma Pleomórfico/patología , Carcinoma Adenoide Quístico/patología , Carcinoma Mucoepidermoide/patología , Tejido AdiposoRESUMEN
Temporomandibular joint osteoarthrosis (TMJ-OA) frequently causes mild, moderate, or severe condylar morphological changes. A novel condylar remodelling scoring system (CRSS) based on three-dimensional cone beam computed tomography images is proposed, which is used to grade condylar morphological changes. In the CRSS, the condyle is divided into 10 regions by 11 reference points. For each increase in the number of regions involved in TMJ-OA, one point is subtracted from the full score of 10. The intra-class correlation coefficients for intra- and inter-observer agreement (range 0.656-0.898 and 0.841-0.906, respectively) indicated that the CRSS had good reliability. Cephalometric analysis showed that the condyles with severe morphological changes were prone to present with a retrognathic and clockwise rotating mandible, shorter ramus height, reduced mandibular length, larger mandibular angle, and maxillary retrusion. Qualitative CRSS evaluation and quantitative volumetric analysis were performed to evaluate the stability of severe TMJ-OA in its natural course (343 condyles). The continuous cortex group showed no remarkable changes with an average follow-up of 2 years. In the discontinuous cortex group, most (74.4%) converted into a continuous cortex during follow-up (mean 2 years).
Asunto(s)
Osteoartritis , Trastornos de la Articulación Temporomandibular , Humanos , Cóndilo Mandibular/diagnóstico por imagen , Reproducibilidad de los Resultados , Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Osteoartritis/diagnóstico por imagenRESUMEN
Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 µg/Lã0.13 µg/LAsunto(s)
Hormona de Crecimiento Humana
, Síndrome Metabólico
, Adulto
, HDL-Colesterol
, Humanos
, Masculino
, Síndrome Metabólico/complicaciones
, Persona de Mediana Edad
, Factores de Riesgo
, Triglicéridos
RESUMEN
OBJECTIVE: To establish a Parotid Imaging Reporting and Data System (PI-RADS) for CT diagnosis of the parotid gland neoplasms and to investigate the clinical applicable value and feasibility of PI-RADS. METHODS: Patients who had been diagnosed with primary parotid gland neoplasms and had received surgical treatments in Peking University School and Hospital of Stomatology during the period of January 2013 to December 2016 were included in this study. The diagnoses were confirmed by the postoperative pathological examinations in all the patients. The CT imaging data of all patients were retrospectively reviewed and analyzed by two readers in consensus. Imaging characteristics related to the parotid neoplasms were extracted and quantified. Based on comprehensive analysis of the imaging characteristics, the probabilities of the benign and malignant neoplasms were evaluated and classified into six grades, PI-RADS 1-6 (PI-RADS 1: normal parotid gland; PI-RADS 2: confidently benign lesions; PI-RADS 3: probably benign lesions without confirmed evidence of malignancy; PI-RADS 4: suspected malignancy without sufficient evidence of malignancy; PI-RADS 5: confidently malignant lesions; PI-RADS 6: lesions with confirmed pathological evidence of malignancy). RESULTS: A total of 897 patients with 1 003 parotid lesions were included. The lesions included 905 benign and 98 malignant lesions. The proportions of the malignancies in PI-RADS 2, PI-RADS 3, PI-RADS 4 and PI-RADS 5 according to the two readers in consensus were 0.4%, 5.7%, 35.5% and 96.7% respectively. The overall Cohen's Kappa test showed medium consistency between the two independent researchers (κ=0.614, P<0.001, 95%CI: 0.569-0.695). Pearson Chi-square test showed that the proportions of malignancies increased with the diagnostic PI-RADS grades (Cochran-Armitage trend test, Z=-15.579, P<0.001). The results of Pearson Chi-square tests showed significant differences between the grades [PI-RADS 2 and 3 (χ²=12.048, P=0.001); PI-RADS 3 and 4 (χ²=75.231, P<0.001); PI-RADS 4 and 5 (χ²=32.266, P<0.001)]. CONCLUSION: PI-RADS can be used to evaluate the risk of malignancy and will be helpful to improve the imaging diagnosis and clinical treatment of parotid gland neoplasms.
Asunto(s)
Glándula Parótida/diagnóstico por imagen , Neoplasias de la Parótida , Neoplasias de la Próstata , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To investigate the BRAF gene mutations in ameloblastic fibroma (AF), and to further analyze the relationship between the BRAF mutation and clinical characteristics so as to provide new reference to the study of AF's molecular pathology. METHODS: Sixteen cases diagnosed as AF at the Department of Oral Pathology, Peking University School of Stomatology between January 1990 and December 2017 were collected. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues using the QIAamp DNA Mini Kit (Qiagen, Germany) according to the manufacturer's instructions. Polymerase chain reaction (PCR) and direct sequencings were used to detect the BRAF gene mutations. The clinicopathological data, such as the age, location of the lesion, symptoms and treatments were retrospectively analyzed. RESULTS: The sixteen cases of AF involved nine women and seven men aged 2-67 years. Three lesions occurred in the maxilla and thirteen in the mandible. The most common presenting symptom of AF was a painless slowly enlarging mass with swelling. Ten patients received conservative treatment and the other six patients received radical surgery. Three cases relapsed during the study period. BRAF gene mutation was found in sixteen of all the sixteen samples analyzed (100%). The BRAF mutation was a point mutation with a thymine-adenine transversion at nucleotide 1 799 of 15 exons, resulting in a change at residue 600 that substituted glutamine for valine. This mutation was the strongest activator of the downstream RAS/RAF/MEK/ERK-MAPK signaling pathway. This helped to bring about a gain-of-function mutation due to a V600E substitution. Many studies identified that BRAF regulated survival, apoptosis, and proliferation of cells by inducing MAPK pathways activation. For the existing cases, none of the age, sex, location, recurrence and treatments had a statistically significant correlation with BRAF mutation. CONCLUSION: Our findings demonstrated high prevalence of BRAF V600E mutation in AF. The pathogenic role remains to be clarifiedï¼.
Asunto(s)
Fibroma , Proteínas Proto-Oncogénicas B-raf/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Exones , Femenino , Fibroma/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Adulto JovenRESUMEN
V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a pro-oncogene, which is one member of the RAF family. Mutated BRAF is found in approximately 8% of human tumors. BRAF gene mutations lead to continuous activation of the mitogen-activatd protein kinase (MAPK) pathway, which resulting in abnormal cell proliferation and tumorigenesis. In recent years, recurrent MAPK signaling mutations were identified in ameloblastoma, among which BRAF-V600E is the most prominent type. This provides new strategies for the targeted treatment of ameloblastoma. This paper reviewed the latest advances in BRAF gene mutation associated with ameloblastoma and its potential clinical significance.
Asunto(s)
Ameloblastoma/genética , Neoplasias Maxilomandibulares/genética , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Animales , Humanos , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Investigación/tendencias , Transducción de SeñalRESUMEN
BACKGROUND: The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. METHODS: Data were obtained from the Western Australian Pregnancy Cohort (Raine) Study, with language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E] and Total [CELF-T]) and cognition (Coloured Progressive Matrices [CPM]) assessed at age 10 yr. Medical records were reviewed, and children divided into quartiles based on total VA exposure duration before age three yr. The association between test score and exposure duration quartile was evaluated using linear regression, adjusting for patient characteristics and comorbidity. RESULTS: Of 1622 children with available test scores, 148 had documented VA exposure and were split into the following quartiles: ≤25, >25 to ≤35, >35 to ≤60 and >60 min. Compared with unexposed children, CELF-T scores for children in the first and second quartiles did not differ, but those in the third and fourth quartiles had significantly lower scores ([3 rd quartile - Unexposed] -5.3; 95% confidence interval [CI], (-10.2 - -0.4), [4 th quartile - Unexposed] -6.2; 95% CI, (-11.6 - -0.9). CELF-E showed similar findings, but significant differences were not found in CELF-R or CPM for any quartile. CONCLUSIONS: Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.
Asunto(s)
Anestésicos Generales/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Lenguaje/inducido químicamente , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pruebas Neuropsicológicas , Estudios Retrospectivos , Factores de Tiempo , Australia Occidental , Adulto JovenRESUMEN
OBJECTIVES: We aimed to investigate the possible effects of vimentin (Vim) and citrullinated Vim (cVim) on proliferation capacity, pro-inflammatory cytokine secretion, and the expression of peptidylarginine deiminase type 4 (PADI4) and receptor activator of nuclear factor kappa B ligand (RANKL) in cultured fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHOD: Human native Vim was citrullinated with rabbit PAD in vitro and detected using a Western blot assay with anti-modified citrulline antibody (anti-MC Ab). FLSs from RA or OA synovial samples were stimulated with Vim or cVim. Cell proliferation capacity was determined using the Celltiter 96 AQueous cell proliferation assay. The concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of PADI4 and RANKL was measured by real-time polymerase chain reaction (RT-PCR) and a Western blot assay. RESULTS: Our Western blot assay with anti-MC Ab indicated that the amount of cVim increased significantly after Vim had been incubated with rabbit PAD in vitro. The proliferation capacity and secretion of TNF-α and IL-1 were significantly enhanced in the FLSs of RA patients when treated with cVim. However, when treated with Vim, an inhibitory effect on the proliferation capacity was noted in the FLSs from RA and also from OA patients. cVim significantly increased the expression of PADI4 and RANKL in the FLSs from RA patients. CONCLUSION: cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients.
Asunto(s)
Artritis Reumatoide/metabolismo , Proliferación Celular/efectos de los fármacos , Hidrolasas/metabolismo , Ligando RANK/metabolismo , Membrana Sinovial/efectos de los fármacos , Vimentina/farmacología , Anciano , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Interleucina-1/metabolismo , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Osteoartritis/inmunología , Osteoartritis/metabolismo , Osteoartritis/patología , Arginina Deiminasa Proteína-Tipo 4 , Desiminasas de la Arginina Proteica , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
To evaluate the association of single-nucleotide polymorphisms (SNPs) in PADI4 mRNA with rheumatoid arthritis (RA) in a Chinese population, we examined the distribution of four exonic SNPs of the PADI4 gene (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C and padi4_104*T/C) and PADI4 gene expression in 70 RA patients and 81 controls. Increased RA susceptibility was associated with the minor alleles of padi4_89 (P = 0.012), padi4_90 (P = 0.002), padi4_104 (P = 0.001) and the functional haplotype carrying the four minor alleles (P = 0.008). Human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles were also associated with increased RA susceptibility, and the individuals with minor alleles of four exonic SNPs and SE alleles showed more increased RA susceptibility. The PADI4 expression was significantly higher in RA patients than in controls (P < 0.001). HLA-DRB1 SE alleles and the genotypes carrying the minor alleles of four SNPs were associated with increased PADI4 expression. It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.
Asunto(s)
Artritis Reumatoide/genética , Antígenos HLA-DR/genética , Haplotipos/genética , Hidrolasas/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Artritis Reumatoide/epidemiología , China/epidemiología , Susceptibilidad a Enfermedades , Femenino , Frecuencia de los Genes , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad , Arginina Deiminasa Proteína-Tipo 4 , Desiminasas de la Arginina ProteicaRESUMEN
UNLABELLED: Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. ABBREVIATIONS: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.
Asunto(s)
Síndrome del Nevo Basocelular/complicaciones , Neoplasias Maxilomandibulares/genética , Tumores Odontogénicos/genética , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G/genética , Adolescente , Adulto , Anciano , Síndrome del Nevo Basocelular/genética , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Neoplasias Maxilomandibulares/complicaciones , Queratinas , Masculino , Persona de Mediana Edad , Mutación , Tumores Odontogénicos/complicaciones , Receptores Patched , Receptor Patched-1 , Receptor SmoothenedRESUMEN
OBJECTIVES: PTCH, the human homologue of the Drosophila segment polarity gene, patched, has been identified as the gene responsible for nevoid basal cell carcinoma syndrome. The aim of this study was to investigate PTCH gene mutation in Chinese patients with nevoid basal cell carcinoma syndrome. MATERIALS AND METHODS: DNA was isolated from both odontogenic keratocyst tissue and peripheral blood of five patients with syndrome and one patient with only multiple odontogenic keratocysts, and mutational analysis of the PTCH gene performed by direct sequencing after amplification of all 23 exons by polymerase chain reaction (PCR). RESULTS: A previously reported germline mutation (c.2619C>A) was identified in two familial cases involving the mother and the daughter, with the mother also carrying a novel somatic mutation (c.361_362insGAGC). Three novel germline PTCH mutations (c.1338_1339insGCG, c.331delG and c.1939A>T) were detected in three unrelated patients with syndrome. The patient with multiple odontogenic keratocysts who failed to fulfill the diagnostic criteria of the syndrome also carried a novel germline mutation (c.317T>G). CONCLUSION: The frequent germline PTCH mutations detected in our series provide further evidence for the crucial role of PTCH in the pathogenesis of nevoid basal cell carcinoma syndrome in Chinese.
Asunto(s)
Síndrome del Nevo Basocelular/genética , Mutación de Línea Germinal/genética , Quistes Odontogénicos/genética , Tumores Odontogénicos/genética , Receptores de Superficie Celular/genética , Adolescente , Adulto , Síndrome del Nevo Basocelular/complicaciones , Síndrome del Nevo Basocelular/etnología , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense/genética , Quistes Odontogénicos/complicaciones , Tumores Odontogénicos/complicaciones , Receptores Patched , Receptor Patched-1 , Linaje , Valores de ReferenciaRESUMEN
Odontogenic keratocysts are relatively common lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (or Gorlin syndrome). The PTCH gene has been reported to be associated with Gorlin syndrome. We investigated 10 cases of non-syndromic keratocysts and two other cases associated with Gorlin syndrome, looking for PTCH mutations. Four novel and 1 known PTCH mutations were identified in five individual patients. Of the 5 mutations identified, 2 were germ-line mutations (2619C>A; 1338_1339insGCG) in 2 cysts associated with Gorlin syndrome, and 3 were somatic mutations (3124_3129dupGTGTGC; 1361_1364delGTCT; 3913G>T) in 3 non-syndromic cysts. This report describes PTCH mutations in both non-syndromic and Gorlin-syndrome-related odontogenic keratocysts in Chinese patients, and suggests that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts.
Asunto(s)
Síndrome del Nevo Basocelular/genética , Quistes Odontogénicos/genética , Receptores de Superficie Celular/genética , Adolescente , Adulto , Pueblo Asiatico/genética , China , Análisis Mutacional de ADN , Femenino , Humanos , Queratinas , Masculino , Persona de Mediana Edad , Mutación , Receptores Patched , Receptor Patched-1 , Polimorfismo GenéticoRESUMEN
We have previously demonstrated that both basal and isoproterenol-stimulated activities of myocardial adenylyl cyclase were greater in cyanotic patients with tetralogy of Fallet (TOF) than those in acyanotic patients. However, it was not determined whether increased enzyme activity was related to a similar increase in adenylyl cyclase protein and mRNA expression. In the current study, we examined the mRNA and protein expression of cardiac adenylyl cyclase, types V and VI, in cyanotic and acyanotic patients with TOF. Ribonuclease protection assays and immunoblotting were performed on myocardial specimens obtained from cyanotic patients with TOF and acyanotic patients with TOF or ventricular septal defect. We demonstrated that in both cyanotic and acyanotic patients, there was more type V adenylyl cyclase mRNA than type VI. Types V and VI cardiac adenylyl cyclase mRNA were significantly increased in myocardium of the cyanotic group compared to the acyanotic group. Protein expression of both V and VI adenylyl cyclases was correspondingly upregulated in cyanotic patients compared to acyanotic patients. Our results indicate that gene and protein expression of cardiac adenylyl cyclases, types V and VI, is increased in the cyanotic myocardium. These results suggest that chronic hypoxemia may regulate the expression of adenylyl cyclase enzymes.
Asunto(s)
Adenilil Ciclasas/metabolismo , Cardiopatías Congénitas/enzimología , Isoenzimas/metabolismo , Miocardio/enzimología , ARN Mensajero/metabolismo , Adenilil Ciclasas/análisis , Enfermedad Crónica , Densitometría , Femenino , Humanos , Hipoxia/metabolismo , Immunoblotting , Lactante , Isoenzimas/análisis , Masculino , ARN Mensajero/análisis , Transducción de Señal , Tetralogía de Fallot/complicaciones , Tetralogía de Fallot/enzimología , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVES: Atrial fibrillation remains a significant source of morbidity after coronary artery bypass grafting (CABG). Whether cardiopulmonary bypass (CPB) temperature influences the occurrence of postoperative atrial fibrillation in CABG patients has not been specifically examined. In the present study, we reviewed postoperative data from patients who were prospectively randomized to mild or moderate hypothermic CPB for elective CABG to determine the incidence of postoperative atrial fibrillation. DESIGN: Randomized, single center, observational study. SETTING: Tertiary university medical center. PATIENTS: Adults undergoing elective CABG surgery. INTERVENTIONS: Enrolled patients were prospectively randomized to mild (34 degrees C [93.2 degrees F]) or moderate (28 degrees C [82.4 degrees F]) hypothermic CPB. MEASUREMENTS AND MAIN RESULTS: The incidence of postoperative atrial fibrillation was determined by review of ICU and hospital records. There was a significantly higher incidence of atrial fibrillation in the moderate compared with the mild hypothermic CPB group. Patients who had postoperative atrial fibrillation were significantly older than those without atrial fibrillation. Furthermore, a significant increase in the relative risk of developing postoperative atrial fibrillation was found for both age and CPB temperature. CONCLUSIONS: Our results indicate that the temperature of systemic cooling during CPB is an important factor in the development of atrial fibrillation after CABG surgery. In addition, this study confirms that increasing age is a significant determinant of postoperative atrial fibrillation.
Asunto(s)
Fibrilación Atrial/etiología , Puente Cardiopulmonar/efectos adversos , Hipotermia Inducida/efectos adversos , Hipotermia Inducida/métodos , Adulto , Distribución por Edad , Factores de Edad , Anciano , Puente de Arteria Coronaria , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Morbilidad , Estudios Prospectivos , Factores de Riesgo , TemperaturaRESUMEN
UNLABELLED: Cardiac dysfunction occurs in infants with prenatal cocaine exposure, and gestational cocaine exposure induces presynaptic and postsynaptic changes in the central monoaminergic receptor pathways. The hypothesis of this study is that prenatal cocaine exposure adversely affects the peripheral adrenergic receptor (betaAR) signaling pathway in the neonatal rat heart. Timed pregnant rats received daily intragastric treatment with saline or cocaine 20 mg/kg or 60 mg/kg from Gestational Day 2 until parturition. After birth, nursing mothers either continued to receive the same treatment or received no treatment. Adenylyl cyclase activity, betaAR density, and the amount of immunoreactive G proteins were measured in myocardial membranes obtained from the offspring on Postnatal Day 1 or 7. On Postnatal Day 1, prenatal cocaine exposure increased the betaAR number but did not affect isoproterenol-stimulated adenylyl cyclase activity. On Postnatal Day 7, perinatal cocaine exposure significantly attenuated isoproterenol-stimulated adenylyl cyclase activity in the absence of betaAR up-regulation. Prenatal cocaine exposure also significantly increased Gi protein and reduced GTP-stimulated adenylyl cyclase activity in Postnatal Day 1 cocaine (20 mg/kg) pups compared with saline (P < 0.05). Therefore, perinatal cocaine exposure impaired the myocardial betaAR-cAMP signaling pathway during the first week of postnatal life in the rat. IMPLICATIONS: This study shows that maternal cocaine use during pregnancy impairs the beta-adrenoceptor signaling pathway in the rat during the first week of life. Abnormal cardiac function in the cocaine-exposed neonate may be related to a defect in beta-adrenoceptors, because they regulate cardiac function.
Asunto(s)
Animales Recién Nacidos/fisiología , Cocaína/toxicidad , Inhibidores de Captación de Dopamina/toxicidad , Corazón/efectos de los fármacos , Miocardio/metabolismo , Receptores Adrenérgicos beta/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Animales , AMP Cíclico/fisiología , Femenino , Proteínas de Unión al GTP/fisiología , Corazón/inervación , Immunoblotting , Miocardio/enzimología , Embarazo , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-DawleyRESUMEN
beta-Adrenergic receptor (betaAR) desensitization is the decrease in response following sustained agonist stimulation by catecholamines. While developmental changes in betaAR response have been well documented in the mammalian heart, much less is known regarding the regulation of betaAR function in immature hearts. The purpose of the present study was to determine whether there are developmental differences in myocardial betaAR desensitization. We used an isolated heart preparation to examine the betaAR-mediated inotropic response before and after sustained exposure to 1 microM isoproterenol in adult and neonatal rabbits. We also assayed the adenylyl cyclase activity and performed radioligand-binding studies to determine betaAR characteristics in adult and neonatal ventricular tissues with and without exposure to isoproterenol. Both adult and neonatal rabbit hearts showed a concentration-dependent increase in systolic function, namely, isovolumic left ventricular developed pressure (LVDP) and maximal positive dP/dt of LVDP (dP/dt(max)) in response to isoproterenol. Adults, however, showed a significantly greater response than neonates. After sustained exposure to isoproterenol, the subsequent betaAR-mediated responses in LVDP and dP/dt(max) were significantly attenuated in adults, but much less so in neonates. The adenylyl cyclase activity in response to isoproterenol was significantly different between adult, but comparable in neonatal tissues both exposed or not to isoproterenol. The total betaAR density was higher in neonatal than in adult tissues without isoproterenol exposure, but there was no significant change in betaAR density in either group following isoproterenol exposure. In addition, isoproterenol exposure increased the amount of the inhibitory G protein in adult, but not neonatal tissues. Our results suggest that there were developmental differences in myocardial betaAR functional responses in betaAR desensitization.
Asunto(s)
Envejecimiento , Animales Recién Nacidos/fisiología , Miocardio/metabolismo , Receptores Adrenérgicos beta/fisiología , Adenilil Ciclasas/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Proteínas de Unión al GTP/análisis , Isoproterenol/farmacología , Contracción Miocárdica , Miocardio/química , Presión , Conejos , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: To perform preoperative airway evaluations, using radiographic analysis, to review the tracheal anatomy in children with congenital cardiac disease. DESIGN: Prospective. SETTING: A university children's hospital. PARTICIPANTS: One hundred patients. MEASUREMENTS AND MAIN RESULTS: One magnified airway film (high kilovoltage filtered) was performed preoperatively on 100 consecutive children presenting for repair of congenital cardiac disease. Events at intubation, with respect to endotracheal tube size (internal diameter in millimeters) and difficulties with placement of the tube, were recorded. Postoperative morbidity, specifically related to underlying airway anomaly, was documented. Eleven children had positive radiographic findings after review of magnified airway films. Six of 11 patients had evidence of tracheobronchial pathology, and five patients had no tracheal pathology. Difficulties with intubation were noted in two children. No perioperative morbidity was noted in any patient. CONCLUSION: The use of preoperative magnified airway films for tracheal evaluations in children with cardiac disease should be considered.
Asunto(s)
Cardiopatías Congénitas/patología , Tráquea/anomalías , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Estudios ProspectivosRESUMEN
Pregnant rats received saline once daily (Control QD) or twice daily (Control BID), cocaine 2 mg/kg IV daily (COC QD) or twice daily (COC BID) throughout gestation beginning on gestational day 4. The treatment was continued in nursing mothers until postnatal day 7. All studies were performed in their offsprings on postnatal days 1 and 7. An age-dependent increase in heart rate was observed from D1 to D7 in all four groups of animals. Cocaine exposure significantly increased heart rate in the once daily treatment group on D1 and D7. In contrast, twice daily cocaine exposure did not alter heart rate. Maturational changes in heart rate variability (HRV) were also documented. Low-frequency (LF: 0.25-0.8 Hz) power of HRV is a marker of both sympathetic and parasympathetic influences. and high-frequency (HF: 0.8-2.4 Hz) power is a marker of efferent vagal activity. Total power (TP) is the sum of LF and HF. TP, normalized units of LF (LF as percent of TP), and normalized HF power decreased from D1 to D7 in all groups. Cocaine treatment affected both LF and HF powers and there was an interaction between cocaine treatment and age for both LF and HF. Although LF/HF ratio decreased from D1 to D7 in both groups of control animals. LF/HF did not change from D1 to D7 in either cocaine-treated group. Thus, cocaine exposure significantly attenuated the age-dependent change in LF/HF. Our results indicated that there were normal developmental changes in HRV consistent with continued postnatal development of autonomic nervous system. Perinatal cocaine exposure appeared to modify these changes. The specific autonomic mechanism for the cocaine effect may be a decline in parasympathetic activity and a concomitant change in sympathetic activity.
Asunto(s)
Cocaína/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Peso al Nacer , Peso Corporal/efectos de los fármacos , Femenino , Lactancia , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
The cardiac alpha1-adrenergic chronotropic response changes from stimulatory to inhibitory post-natally. The mature inhibitory response is mediated by the alpha1B-adrenoceptor and a pertussis toxin sensitive G protein. In vivo and in vitro studies identify sympathetic innervation as critical for the maturation of this inhibitory response. Additional experiments in a culture model indicate the effect of innervation is dependent on neurally released neuropeptide Y. The present study establishes that the individual signaling elements in the neuropeptide Y induced alpha1-adrenergic cascade are the same as those appearing during normal in vivo development. In addition, the data demonstrate that the effect of neuropeptide Y does not result from activation of the putative cardiac Y3 neuropeptide Y receptor subtype, since it is reproduced by the peptide fragment neuropeptide Y-(13-36) but not by [Leu31, Pro34]neuropeptide Y.
Asunto(s)
Proteínas de Unión al GTP/fisiología , Frecuencia Cardíaca/fisiología , Corazón/efectos de los fármacos , Neuropéptido Y/farmacología , Receptores Adrenérgicos alfa 1/fisiología , Receptores de Neuropéptido Y/fisiología , Animales , Animales Lactantes , Células Cultivadas , Proteínas de Unión al GTP/efectos de los fármacos , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Toxina del Pertussis , Fenilefrina/farmacología , Ratas , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores de Neuropéptido Y/efectos de los fármacos , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
BACKGROUND: Exposure to environmental tobacco smoke is associated with detrimental effects on pulmonary function in children. The authors investigated the relation between airway complications in children receiving general anesthesia and the passive inhalation of tobacco smoke. METHODS: Six hundred two children scheduled to receive general anesthesia were enrolled in this prospective study. The anesthesiologist and the recovery room nurse, unaware of the smoke exposure history, recorded the occurrence of airway complications. A history of passive smoking was assessed by measuring the urinary concentration of the major nicotine metabolite cotinine and by questionnaire. RESULTS: Airway complications occurred in 42% of the patients with urinary concentrations of cotinine > or =40 ng/ml, in 33% of the patients with concentrations of cotinine between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender of the child (P = 0.001) and the educational level of the child's mother (P = 0.0008) significantly modified the effect of the concentration of cotinine on the incidence of adverse respiratory events. CONCLUSIONS: There is a strong association between passive inhalation of tobacco smoke and airway complications in children receiving general anesthesia. The relationship is greatest for girls and for those whose mothers have a lower level of education. Passive smoking should be regarded as a risk factor in children undergoing general anesthesia.