RESUMEN
AIM: Postpartum depression (PPD) may have negative effects on the parents and lead to impaired cognitive, socioemotional, and behavioral development in their children. The purpose of this study was to examine factors associated with PPD in parents during the first year after delivery. METHODS: This study used a self-administered questionnaire. Questionnaires were mailed at 5 days, 3 months, 6 months, and 1 year after delivery, respectively. The particpants were 107 pairs of mothers and fathers. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Data on sense of coherence (SOC), Quality Marriage Index, Social Support Scale, Mother-to-Infant Bonding Scale, and sociodemographic variables were collected. Multiple regression analysis was performed to examine the strength of the association between several variables and the EPDS at each survey period for fathers and mothers, respectively. RESULTS: The prevalence of PPD in the first-year postpartum ranged from 12.1%-23.4% to 7.5%-8.4% for fathers and mothers, respectively. SOC had the strongest impact on EPDS scores for both fathers and mothers at all four survey periods. CONCLUSIONS: Our findings suggest that stress coping skills are an important factor affecting PPD throughout the first-year postpartum for both fathers and mothers.
Asunto(s)
Depresión Posparto , Padres , Femenino , Humanos , Lactante , Masculino , Depresión Posparto/epidemiología , Depresión Posparto/psicología , Pueblos del Este de Asia , Estudios Longitudinales , Estudios Prospectivos , Padres/psicologíaRESUMEN
Drug-induced block of the cardiac rapid delayed rectifying potassium current (I Kr), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Here we propose a mechanism that could explain why certain clinically used hERG blockers are less proarrhythmic than others. We demonstrate that several drugs that block hERG channels, but have favorable cardiac safety profiles, also evoke another effect; they facilitate the hERG current amplitude in response to low-voltage depolarization. To investigate how hERG facilitation impacts cardiac safety, we develop computational models of I Kr block with and without this facilitation. We constrain the models using data from voltage clamp recordings of hERG block and facilitation by nifekalant, a safe class III antiarrhythmic agent. Human ventricular action potential simulations demonstrate the ability of nifekalant to suppress ectopic excitations, with or without facilitation. Without facilitation, excessive I Kr block evokes early afterdepolarizations, which cause lethal arrhythmias. When facilitation is introduced, early afterdepolarizations are prevented at the same degree of block. Facilitation appears to prevent early afterdepolarizations by increasing I Kr during the repolarization phase of action potentials. We empirically test this prediction in isolated rabbit ventricular myocytes and find that action potential prolongation with nifekalant is less likely to induce early afterdepolarization than action potential prolongation with dofetilide, a hERG channel blocker that does not induce facilitation. Our data suggest that hERG channel blockers that induce facilitation increase the repolarization reserve of cardiac myocytes, rendering them less likely to trigger lethal ventricular arrhythmias.
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Potenciales de Acción , Antiarrítmicos/farmacología , Canal de Potasio ERG1/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Bloqueadores de los Canales de Potasio/farmacología , Animales , Células Cultivadas , Canal de Potasio ERG1/antagonistas & inhibidores , Células HEK293 , Humanos , Miocitos Cardíacos/fisiología , Fenetilaminas/farmacología , Pirimidinonas/farmacología , Conejos , Sulfonamidas/farmacología , XenopusRESUMEN
Human ether-a-go-go-related gene (hERG) channels play a critical role in cardiac action potential repolarization. The unintended block of hERG channels by compounds can prolong the cardiac action potential duration and induce arrhythmia. Several compounds not only block hERG channels but also enhance channel activation after the application of a depolarizing voltage step. This is referred to as facilitation. In this study, we tried to extract the property of compounds that induce hERG channel facilitation. We first examined the facilitation effects of structurally diverse hERG channel blockers in Xenopus oocytes. Ten of 13 assayed compounds allowed facilitation, suggesting that it is an effect common to most hERG channel blockers. We constructed a pharmacophore model for hERG channel facilitation. The model consisted of one positively ionizable feature and three hydrophobic features. Verification experiments suggest that the model well describes the structure-activity relationship for facilitation. Comparison of the pharmacophore for facilitation with that for hERG channel block showed that the spatial arrangement of features is clearly different. It is therefore conceivable that two different interactions of a compound with hERG channels exert two pharmacological effects, block and facilitation.
Asunto(s)
Canales de Potasio Éter-A-Go-Go/fisiología , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/farmacología , Relación Estructura-Actividad Cuantitativa , Animales , Atenolol/química , Atenolol/farmacología , Clorfeniramina/química , Clorfeniramina/farmacología , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Fluoxetina/química , Fluoxetina/farmacología , Haloperidol/química , Haloperidol/farmacología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Imipramina/química , Imipramina/farmacología , Metoprolol/química , Metoprolol/farmacología , Nortriptilina/química , Nortriptilina/farmacología , Prometazina/química , Prometazina/farmacología , Propranolol/química , Propranolol/farmacología , Sotalol/química , Sotalol/farmacología , Terfenadina/química , Terfenadina/farmacología , Verapamilo/química , Verapamilo/farmacología , Xenopus laevisRESUMEN
Nifekalant and azimilide, Class III antiarrhythmic agents, block the human ether-à-go-go-related gene K(+) (hERG) channel. However, when a depolarizing membrane potential is applied, they also increase the current at low potentials by shifting its activation curve towards hyperpolarizing voltages. This phenomenon is called 'facilitation'. In this study, we tried to address the mechanism underlying the facilitation by analyzing the effects of various compounds on hERG expressed in Xenopus oocytes. Like nifekalant, amiodarone, quinidine and carvedilol, but not by dofetilide, caused the current facilitation of hERG, suggesting that the facilitation is a common effect to a subset of hERG blockers. As the concentration of each compound was increased, the total hERG current was suppressed progressively, while the current at low potentials was augmented. Activation curves of the remaining hERG current in the facilitation condition could be described as the sum of two Boltzmann functions reflecting two populations of hERG currents having different activation curves. The voltage shift in the activation curve from control was constant for each compound even at different concentrations; -31 mV in amiodarone, -27 mV in nifekalant, -17 mV in quinidine and -12 mV in carvedilol. Therefore, the facilitation is based on the appearance of hERG whose voltage-dependence for the activation is shifted towards hyperpolarizing voltages.
Asunto(s)
Antiarrítmicos/farmacología , Canales de Potasio Éter-A-Go-Go/agonistas , Amiodarona/farmacología , Animales , Canal de Potasio ERG1 , Humanos , Hidantoínas , Imidazolidinas/farmacología , Potenciales de la Membrana/efectos de los fármacos , Piperazinas/farmacología , Pirimidinonas/farmacología , Xenopus laevisRESUMEN
BACKGROUND: Systemic administration of corticosteroid, plasmapheresis and high-dose immunoglobulin therapy (IVIG) are the main treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVE: To evaluate the effects of the treatments of SJS and TEN. METHODS: Twenty-seven cases of SJS and 19 cases of TEN treated in our hospitals from 2000 to 2007 were analyzed. RESULTS: Corticosteroid was administered systemically in all cases except one case of TEN which developed methicillin resistant staphylococcus aureus (MRSA) pneumoniae before the onset of the eruption. Methylprednisolone (mPSL) pulse therapy (1000 mg/day) or mini pulse therapy (less than 600 mg/day of mPSL) was selected by 8 cases of SJS and 9 cases of TEN. Combination of plasmapheresis or IVIG with corticosteroid therapy was performed in 3 cases of SJS and 8 cases of TEN. The mortality rate of patient with SJS was 3.7% (1 case), and with TEN was 21.1% (4 cases). The deceased case of SJS had been treated with corticosteroid alone and died for acute respiratory disorder after 24 days from the onset of the eruption. Four deceased cases of TEN were treated with corticosteroids with or without IVIG, and 2 of them merged sepsis. CONCLUSIONS: Although corticosteroids may enhance the risk of sepsis, prompt treatment with systemic corticosteroids seems to reduces morbidity and improves outcome of SJS and TEN patients.
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Síndrome de Stevens-Johnson/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inmunoglobulinas/uso terapéutico , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Intercambio Plasmático , Pronóstico , Quimioterapia por PulsoRESUMEN
BACKGROUND: Carmine is a natural red pigment obtained from dried gravid female cochineal insects (Dactylopius coccus or Coccus cacti). There have been several reports of allergies to carmine, but the major allergens responsible have not been identified. OBJECTIVE: To identify the major allergenic proteins in cochineal. METHODS: Immunoblots of purified cochineal extract were probed with sera from 3 patients with allergy. Partial amino acid sequences were determined for the proteins bound by IgE, and the corresponding cDNA, containing a complete coding region, was cloned by 5' and 3' rapid cDNA extension and PCR. The recombinant protein was expressed in yeast and subjected to immunoblotting. RESULTS: We identified a full-length cDNA encoding a protein, which we named CC38K, with 335 amino acids and a molecular mass calculated as 38 kd. This amino acid sequence included all the partial amino acid sequences obtained from the purified proteins identified by IgE from patients with allergy. Recombinant CC38K protein was recognized by patients' sera, indicating that this is a major allergen present in carmine. The CC38K sequence showed homology to phospholipases. CONCLUSION: We have, for the first time, identified the major allergen in cochineal extract. This protein may be a phospholipase or related enzyme, both of which are known to be allergens in other insects.
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Alérgenos/inmunología , Carmín/análogos & derivados , Colorantes/efectos adversos , Hipersensibilidad a los Alimentos/inmunología , Adulto , Alérgenos/química , Alérgenos/genética , Secuencia de Aminoácidos , Secuencia de Bases , Carmín/efectos adversos , Clonación Molecular , Femenino , Humanos , Inmunoglobulina E/sangre , Persona de Mediana Edad , Datos de Secuencia Molecular , Alineación de SecuenciaAsunto(s)
Carmín/análogos & derivados , Colorantes/efectos adversos , Hipersensibilidad Inmediata/etiología , Adulto , Animales , Bebidas/efectos adversos , Carmín/efectos adversos , Femenino , Hemípteros/inmunología , Humanos , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/sangre , Persona de Mediana EdadRESUMEN
Cutaneous pseudolymphomas (CPL) are benign cutaneous lymphoproliferative infiltrations of various origin, including among others bacterial infections, viral infections and drugs . Helicobacter pylori has been frequently founded in the stomach of patients with MALT lymphoma. In January 2001, a 43-year-old man was referred to our department because of a 1-month history of itchy erythematous patches, plaques and flat tumors on his body. Histological examination revealed nodular infiltrations composed of lymphocytes, plasma cells and histiocytes with exocytosis of lymphocytes within the epidermis. Molecular analysis of rearrangement of T cell receptor and immunoglobulin heavy-chain genes did not reveal monoclonality. Based on these clinical, laboratory and histopathological data, a diagnosis of cutaneous T cell pseudolymphoma (CTPL) was made. The patient was anti-H. pylori antibody-positive, and was treated with anti-H. pylori combination with the result that all of the tumors had disappeared by January 2002. The patient has maintained complete response up to the last follow-up visit in December 2005.
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Anticuerpos Antibacterianos/análisis , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Seudolinfoma/complicaciones , Enfermedades de la Piel/complicaciones , Adulto , Diagnóstico Diferencial , Estudios de Seguimiento , Mucosa Gástrica/microbiología , Gastroscopía , Infecciones por Helicobacter/microbiología , Helicobacter pylori/inmunología , Humanos , Masculino , Seudolinfoma/patología , Enfermedades de la Piel/patologíaRESUMEN
Drug-induced hypersensitivity syndrome (DIHS), characterized by serious adverse systemic reactions in addition to skin rash, has unknown pathogenesis. Its association with human herpesvirus (HHV), mainly HHV-6, has been reported recently. A 46-year-old Japanese man is described in whom a generalized eruption developed about 1 month after taking cyanamide, a drug for alcoholism. This was associated with the following manifestations: high fever, lymphadenopathy, facial edema, marked leukocytosis with eosinophilia and atypical lymphocytes, lymphocytopenia, liver and renal dysfunction, and low IgG level. He was treated with 8 mg betamethasone daily and his condition improved, but he needed low-dose corticosteroid for almost 1 year because of several episodes of recurrence. HHV-6, HHV-7, herpes simplex virus (HSV), and cytomegalovirus (CMV) specific IgG titers showed more than a four-fold rise sequentially. Significant numbers of copies of HHV-6 and HHV-7 DNA were detected in the peripheral white blood cells by real-time polymerase chain reaction (PCR). HHV-6 and CMV DNA were detected in the serum by nested PCR. A patch test for cyanamide was positive. The diagnosis of DIHS due to cyanamide, which has never been reported as a causal drug of DIHS, accompanied by reactivation of not only HHV-6, but also HHV-7, CMV, and HSV, was made. Disturbance of the immune system was suggested by the persistent low level of IgG, and consecutive viral reactivation may have participated in the prolonged course in this case.
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Cianamida/efectos adversos , Hipersensibilidad a las Drogas/etiología , Infecciones por Herpesviridae/virología , Herpesviridae/crecimiento & desarrollo , Activación Viral , Agammaglobulinemia , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Anticuerpos Antivirales/sangre , Betametasona/farmacología , Betametasona/uso terapéutico , Citomegalovirus/aislamiento & purificación , ADN Viral/sangre , Hipersensibilidad a las Drogas/complicaciones , Infecciones por Herpesviridae/etiología , Herpesvirus Humano 6/aislamiento & purificación , Herpesvirus Humano 7/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Pruebas del ParcheAsunto(s)
Anacardium , Hipersensibilidad a los Alimentos/inmunología , Prunus , Adulto , Reacciones Cruzadas , Femenino , HumanosRESUMEN
Lysophosphatidylcholine (lysoPC) acts on vascular smooth muscle cells (VSMCs) to produce a mitogenic response through the activation of extracellular signal-regulated kinases 1/2 (ERK1/2). In the present study, we examined the importance of reactive oxygen species (ROS) in lysoPC-stimulated ERK1/2 activation in cultured rat VSMCs. Treatment with lysoPC for 3 minutes caused a 2-fold increase in intracellular ROS that was blocked by the NADH/NADPH oxidase inhibitor, diphenylene iodonium (DPI). Antioxidants, N-acetyl-L-cysteine, glutathione monoester, or alpha -tocopherol, inhibited ERK1/2 activation by lysoPC. Almost identical results were obtained in the VSMC line A10. Pretreatment of VSMCs with DPI but not allopurinol or potassium cyanide (KCN) abrogated the activation of ERK1/2. The Flag-tagged p47phox expressed in A10 cells was translocated from the cytosol to the membrane after 2 minutes of stimulation with lysoPC. The overexpression of dominant-negative p47phox in A10 cells suppressed lysoPC-induced ERK activation. The ROS-dependent ERK activation by lysoPC seems to involve protein kinase C- and Ras-dependent raf-1 activation. Induction of c-fos expression and enhanced AP-1 binding activity by lysoPC were also inhibited by DPI and NAC. Taken together, these data suggest that ROS generated by NADH/NADPH oxidase contribute to lysoPC-induced activation of ERK1/2 and subsequent growth promotion in VSMCs.