RESUMEN
Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, â¼3 g) can subdue a mouse (â¼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede's venom. The study indicates that centipedes' venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.
Asunto(s)
Venenos de Artrópodos/toxicidad , Artrópodos/fisiología , Canales de Potasio KCNQ/antagonistas & inhibidores , Enfermedades del Sistema Nervioso/inducido químicamente , Conducta Predatoria/efectos de los fármacos , Anomalías del Sistema Respiratorio/inducido químicamente , Animales , Anticonvulsivantes/farmacología , Carbamatos/farmacología , Ratones , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Fenilendiaminas/farmacología , Anomalías del Sistema Respiratorio/tratamiento farmacológico , Anomalías del Sistema Respiratorio/metabolismoRESUMEN
The management of congenital lung malformations is controversial both in the prenatal and postnatal periods. This article attempts to inform best practice by reviewing the level of evidence with regard to prenatal diagnosis, prognosis, and management and postnatal management, including imaging, surgical indication, surgical approach, and risk of malignancy. We present a series of clinically relevant statements along those topics and analyze the evidence for each. In the end, we make a plea for an adequate description of the lesions, both before and after birth, which will allow future comparisons between management options and the initiation of prospective registries.
Asunto(s)
Enfermedades Fetales , Enfermedades del Recién Nacido , Enfermedades Pulmonares , Guías de Práctica Clínica como Asunto , Diagnóstico Prenatal/métodos , Anomalías del Sistema Respiratorio , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/tratamiento farmacológico , Enfermedades Fetales/cirugía , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/cirugía , Enfermedades Pulmonares/congénito , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/cirugía , Embarazo , Diagnóstico Prenatal/normas , Anomalías del Sistema Respiratorio/diagnóstico , Anomalías del Sistema Respiratorio/tratamiento farmacológico , Anomalías del Sistema Respiratorio/cirugíaRESUMEN
BACKGROUND/PURPOSE: Severe pulmonary hypoplasia remains the main cause of the high mortality in newborn infants with congenital diaphragmatic hernia (CDH). Retinoids are a family of molecules derived from vitamin A, which play an important role in lung development. We hypothesized that retinoids promote alveologenesis at the end of gestation and therefore designed this study to investigate the effects of retinoid acid on nitrofen-induced hypoplastic lungs in CDH. METHODS: Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9 of gestation. Retinoic acid 5 mg/kg was given intraperitoneally on days 18, 19, and 20 of gestation and fetuses were recovered on day 21. We had 4 study groups: control (n = 24), control + retinoic acid (n = 22), CDH (n = 24), and CDH + retinoic acid (n = 19). Lungs from the 4 study groups were fixed, and the following stereological measurements were performed on vertical random sections: total lung volume, volume density of airspaces, volume density of air walls, gas exchange surface area, alveolar volume, and total number of alveoli per lung. Total DNA content of each lung was measured using a spectrophotometer. RESULTS: Total lung volume increased in CDH lungs after the addition of retinoic acid but remained the same in the control group. Gas exchange surface area was larger in CDH lungs after the addition of retinoic acid but remained unchanged in the control group. The total number of alveoli per lung was higher after the addition of retinoic acid. Total DNA content as well as total DNA content-lung weight ratio of the left lung increased significantly in the CDH group after the addition of retinoic acid compared with CDH without retinoic acid. CONCLUSIONS: Our results demonstrate that prenatal treatment with retinoic acid stimulates alveologenesis in hypoplastic lungs in CDH.
Asunto(s)
Hernias Diafragmáticas Congénitas , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/embriología , Anomalías del Sistema Respiratorio/prevención & control , Tretinoina/administración & dosificación , Animales , Modelos Animales de Enfermedad , Femenino , Madurez de los Órganos Fetales/efectos de los fármacos , Inyecciones Intraperitoneales , Pulmón/efectos de los fármacos , Pulmón/embriología , Éteres Fenílicos , Embarazo , Preñez , Atención Prenatal , Probabilidad , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Anomalías del Sistema Respiratorio/tratamiento farmacológico , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Retinoids play an important role in lung development. A recent study has demonstrated that prenatal treatment with retinoic acid (RA) stimulates alveologenesis in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia (CDH). Furthermore, it has also been demonstrated that the differentiation from alveolar epithelial cells type II (AECs-II) into alveolar epithelial cells type I (AECs-I), which is the key process in lung development, is disturbed in this model. We hypothesized that retinoids promote alveologenesis by stimulating differentiation of AECs-II to AECs-I at the end of gestation; and therefore, we investigated the effect of RA on the pulmonary expression of intercellular adhesion molecule 1 (ICAM-1), a marker for AECs-I, and thyroid transcription factor 1 (Ttf-1), a marker for AECs-II, in nitrofen-induced hypoplastic lungs. MATERIALS AND METHODS: Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day of gestation (D) 9. Five milligrams per kilogram of RA was given intraperitoneally on D18, D19, and D20; and fetuses were recovered on D21. We had 4 study groups: control (n = 7), control + RA (n = 7), CDH (n = 6), and CDH + RA (n = 6). The expression of ICAM-1 and Ttf-1 was analysed in each lung by real-time reverse transcription polymerase chain reaction and immunohistochemistry. One-way analysis of variance test was used for statistical analysis. RESULTS: Expression levels of ICAM-1 were significantly reduced in CDH lungs compared with normal controls, whereas levels increased significantly in CDH group after the addition of RA (P < .05). Expression levels of Ttf-1 were significantly decreased in lungs from RA-treated CDH animals compared with CDH without RA (P < .05). The ICAM-1 and Ttf-1 immunoreactivity demonstrated similar pattern of expression in various groups. CONCLUSIONS: Our results demonstrate that prenatal treatment with RA accelerates AEC-I proliferation in the hypoplastic lung in CDH.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Hernias Diafragmáticas Congénitas , Pulmón/anomalías , Alveolos Pulmonares/efectos de los fármacos , Anomalías del Sistema Respiratorio/tratamiento farmacológico , Tretinoina/farmacología , Animales , Modelos Animales de Enfermedad , Esquema de Medicación , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Femenino , Hernia Diafragmática/fisiopatología , Inmunohistoquímica , Éteres Fenílicos , Embarazo , Preñez , Atención Prenatal , Probabilidad , Alveolos Pulmonares/citología , ARN Mensajero/análisis , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Anomalías del Sistema Respiratorio/patología , Anomalías del Sistema Respiratorio/prevención & control , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y EspecificidadRESUMEN
Laryngeal web is a rare congenital anomaly. The primary goals of management for congenital laryngeal web are to provide a patent airway and to achieve a good voice quality. However, vocal cords have a tendency for fibrosis and granulation tissue formation after surgical interventions. Traditionally, the treatment of choice for laryngeal web is laryngofissure and placement of a stent or keel. This report presents the successful management of a congenital laryngeal web in a 10-month-old boy with endoscopic lysis and topical mitomycin-C application.
Asunto(s)
Obstrucción de las Vías Aéreas/cirugía , Antibióticos Antineoplásicos/uso terapéutico , Laringoscopía , Laringe/anomalías , Laringe/cirugía , Mitomicina/uso terapéutico , Anomalías del Sistema Respiratorio/cirugía , Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/etiología , Humanos , Lactante , Laringoscopía/métodos , Masculino , Anomalías del Sistema Respiratorio/complicaciones , Anomalías del Sistema Respiratorio/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Contusion spinal cord injury (SCI) at T8 produces respiratory abnormalities in conscious rats breathing room air and challenged with CO2. In seeking ways to improve respiration after SCI, we tested drugs that stimulate serotonin 1A (5-HT1A) receptors, based on our previous findings that these agents can counteract respiratory depression produced by morphine overdose. Respiratory function was measured with a head-out plethysmograph system in conscious rats. T8 SCI rats (n = 5) showed decreased tidal volume (Vt; 0.90 +/- 0.02-0.66 +/- 0.03 ml; p < 0.05) and increased respiratory rate (f;91 +/- 3.7-132 +/- 5.7 breaths/min; p < 0.05) with room air ventilation at 24 hr after injury. They also exhibited a diminished response to the respiratory stimulating effect of 7% CO2; minute ventilation increased to 250 +/- 17 ml/min before, but only to 162 +/- 15 ml/min at 24 hr after SCI (p < 0.05). Respiratory deficits during room air ventilation were also observed at 7 d after injury (n = 3). Treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH-DPAT; 250 microg/kg, i.p.) at 24 hr (n = 5) or 7 d (n = 3) after injury normalized Vt, f, and the respiratory response to 7% CO2. Identical results were obtained with another 5-HT1A receptor agonist, buspirone (1.5 mg/kg, i.p.; n = 3). In contrast, intraperitoneal saline vehicle administration (n = 5) showed no beneficial effects on SCI-impaired respiration. Finally, pretreatment with a specific antagonist of 5-HT1A receptors, 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.; n = 3) given 20 min before 8-OH-DPAT, prevented 8-OH-DPAT from restoring respiration to normal. Our results demonstrate that drugs that stimulate 5-HT1A receptors counteract respiratory abnormalities in conscious rats after SCI.