Collaborative permeation of drug and excipients in transdermal formulations. In vitro scrutiny for ethanol:limonene combinations.

Enhancement of skin permeation of drugs is affected by the simultaneous co-permeation of excipients that hinder the predictivity of in vitro tests. The collaborative effects of two permeation enhancers (ethanol and d-limonene) of a lipophilic drug (alprazolam) have been simultaneously assessed in human skin under different in vitro conditions: integrated setups of diffusion cell experiments with selective concentration gradients of permeants (asymmetric) or without (symmetric) have been combined with coadministration dosages (all-in-one) at different concentrations or short-time skin pretreatment to scrutiny this mutual performance. Findings: Drug permeation is increased under moderated supersaturation but reaches a stationary level above 33 % of its solubility. Ethanol in absence of a concentration gradient increases ca.5 times basal drug permeation. Limonene until 20 % permeates human skin proportionally to its donor concentration but its effect does not depend on ethanol in symmetric conditions and is based on skin imbibition rather than on a carry-on effect. Simultaneous permeation of ethanol and limonene reaches a stationary state after 1.5 h, enough time to achieve maximal enhancement of alprazolam permeation. Additive enhancement is based on ethanol solubilisation maximized by skin saturation of terpene. Complementary analyses of skin disruption published in the literature are in line with these assessments and consolidate them.

Impacto de una modificación de la guía de práctica clínica de la Academia Americana de Pediatría en el manejo de la bronquiolitis aguda grave en una unidad de cuidados intensivos pediátricos / Impact of a modification of the clinical practice guide of the American Academy of Pediatrics in the management of severe acute bronchiolitis in a pediatric intensive care unit

Objetivo: Describir las características y la evolución de los pacientes con bronquiolitis ingresados en una unidad de cuidados intensivos pediátricos. Comparar el tratamiento administrado pre y pospublicación de la guía de práctica clínica de la Academia Americana de Pediatría. Diseño: Estudio descriptivo y observacional realizado entre septiembre de 2010 y septiembre de 2017. Configuración: Unidad de cuidados intensivos pediátricos. Pacientes: Menores de un año con bronquiolitis grave. Intervenciones: Se compararon 2 períodos (2010-14 y 2015-17), antes y después de la modificación del protocolo de manejo de la bronquiolitis en el hospital, según las guías de la Academia Americana de Pediatría. Principales variables: Sexo, edad, comorbilidades, gravedad, etiología, tratamiento administrado, infecciones bacterianas, soporte respiratorio e inotrópico, estancia y mortalidad. Resultados: Se recogieron 706 pacientes, 414 (58,6%) varones, con una mediana de edad de 47 días (RIC 25-100,25). Mediana de escala de gravedad de bronquiolitis (BROSJOD) al ingreso: 9 puntos (RIC 7-11). La etiología por virus respiratorio sincitial se dio en 460 (65,16%) pacientes. El primer período (2010-14) incluyó 340 pacientes y el segundo (2015-17), 366 pacientes. En el segundo período se administraron más nebulizaciones de adrenalina y suero salino hipertónico, y más tratamiento con corticoides. Se usó más ventilación no invasiva y menos ventilación mecánica convencional y precisaron menos soporte inotrópico, sin diferencias significativas. La tasa de antibioterapia disminuyó de forma estadísticamente significativa (p = 0,003). Conclusiones: Pese a la disminución en la antibioterapia, se debería limitar la utilización de nebulizaciones y corticoides en estos pacientes, como recomienda la guía

Objective: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. Design: A descriptive and observational study was carried out between September 2010 and September 2017. Setting: Pediatric intensive care unit. Patients: Infants under one year of age with severe bronchiolitis. Interventions: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. Main variables: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. Results: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (P = .003). Conclusions: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide

Impact of a modification of the clinical practice guide of the American Academy of Pediatrics in the management of severe acute bronchiolitis in a pediatric intensive care unit.

OBJECTIVE: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. DESIGN: A descriptive and observational study was carried out between September 2010 and September 2017. SETTING: Pediatric intensive care unit. PATIENTS: Infants under one year of age with severe bronchiolitis. INTERVENTIONS: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. MAIN VARIABLES: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. RESULTS: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (p=0.003). CONCLUSIONS: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide.

Impact of a modification of the clinical practice guide of the American Academy of Pediatrics in the management of severe acute bronchiolitis in a pediatric intensive care unit. / Impacto de una modificación de la guía de práctica clínica de la Academia Americana de Pediatría en el manejo de la bronquiolitis aguda grave en una unidad de cuidados intensivos pediátricos.

OBJECTIVE: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. DESIGN: A descriptive and observational study was carried out between September 2010 and September 2017. SETTING: Pediatric intensive care unit. PATIENTS: Infants under one year of age with severe bronchiolitis. INTERVENTIONS: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. MAIN VARIABLES: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. RESULTS: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (P=.003). CONCLUSIONS: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide.

The peptide-binding motif of HLA-DR8 shares important structural features with other type 1 diabetes-associated alleles.

The objective of this study was to characterize the peptide-binding motif of the major histocompatibility complex (MHC) class II HLA-DR8 molecule included in the type 1 diabetes-associated haplotype DRB1(*)0801-DQA1(*)0401/DQB1(*)0402 (DR8-DQ4), and compare it with that of other diabetes-associated MHC class II alleles; DR8-bound peptides were eluted from an HLA-DR homozygous lymphoblastoid cell line. The repertoire was characterized by peptide sequencing using a LTQ ion trap mass spectrometer coupled to a multidimensional liquid chromatography system. After validation of the spectra identification, the definition of the HLA-DR8 peptide-binding motif was achieved from the analysis of 486 natural ligands, based on serial alignments of all possible HLA-DR-binding cores. The DR8 motif showed a strong similarity with the peptide-binding motifs of other MHC class II diabetes-associated alleles, HLA-DQ8 and H-2 I-A(g7). Similar to HLA-DQ8 and H-2 I-A(g7), HLA-DR8 preferentially binds peptides with an acidic residue at position P9 of the binding core, indicating that DR8 is the susceptibility component of the DR8-DQ4 haplotype. Indeed, some DR8 peptides were identical to peptides previously identified as DQ8- or I-A(g7) ligands, and several diabetes-specific peptides associated with DQ8 or I-A(g7) could theoretically bind to HLA-DR8. These data further strengthen the association of HLA-DR8 with type I diabetes.

Steroid-sparing effect of mycophenolate mofetil in the treatment of a subepidermal blistering autoimmune disease in a dog.

A 7-year-old female Cocker spaniel-cross was referred with an 8-month history of mucocutaneous erosive dermatitis. On physical examination, skin lesions affected the eyelids and periocular area, lips and vulva. Lesions were symmetrical with small diffuse superficial ulcers, haemorrhagic crusts, adherent purulent exudation in haired skin, and alopecia with hyperpigmentation and scarring. Histopathologic evaluation showed multiple, non-intact dermoepidermal junction vesicles and ulceration associated with a dermal lichenoid infiltrate. Immunohistochemistry showed strong to moderate reactivity in the dermoepidermal junction for the antibodies directed against canine IgG, human IgG lambda light chains and C3, respectively. A diagnosis of autoimmune subepidermal blistering dermatosis was made. Treatment with oral prednisone at 2 mg/kg and mycophenolate mofetil (MMF) at 20 mg/kg twice daily was initiated and after 4 weeks the ulcers and erosions were cured. During the rest of treatment, MMF was maintained at 10 mg/kg twice daily and prednisone could be tapered to 0.25 mg/kg once every other day without recurrences. In conclusion, this case report shows that MMF was well tolerated and might be effective as steroid-sparing agent in the long-term treatment of this autoimmune subepidermal blistering disease.

Comparison of sampling devices for the determination of polychlorinated biphenyls in the sea surface microlayer.

Over 30 sea surface microlayer (SML) samples from two contrasting sites in the North Western Mediterranean -- Barcelona (Spain) and Banyuls-sur-Mer (France) -- were collected using three different sampling devices, namely, glass plate, metal screen (MS) and a surface slick sampler (SS), and compared with the corresponding underlying water (16 samples). The distributions of 41 polychlorinated biphenyl congeners (PCBs) were determined in the different phases: particulate (1.17-10.8 SigmaPCB ng L(-1)), truly dissolved (0.080-16.7 SigmaPCB ng L(-1)) and colloidal matter (1.17-43.0 SigmaPCB ng L(-1)), being the last two estimated from the analysis of the apparently dissolved phase. Concentrations of PCBs in the SML were higher than those in the underlying water (ULW), giving rise to enrichment factors (EF=[C](SML)/[C](ULW)) up to first-order of magnitude. The ANOVA statistical approach was used to assess differences of bulk data (e.g. dissolved organic carbon, DOC; particulate organic carbon, POC; suspended particulate matter, SPM) among sampling devices, whilst p-tailed t paired tests were used in order to compare the enrichments obtained for each sampling date. In this respect, no significantly different enrichment factors were found among sampling devices (p < 0.05), although the surface SS showed lower enrichments, probably due to the dilution of the SML with the ULW during sampling. The MS seemed to be the most suitable device for the determination of PCBs in the SML in terms of sampling efficiency under a variety of meteorological conditions.

Evaluation of sampling devices for the determination of polycyclic aromatic hydrocarbons in surface microlayer coastal waters.

The sea surface microlayer (SML) may play an important role on the transport and fate of persistent organic pollutants in the marine environment. In order to evaluate the appropriateness of a number of sampling devices for the analysis of 14 parent polycyclic aromatic hydrocarbons (3-5 aromatic rings), marine SML waters were sampled using a glass plate, a rotating drum/roller, a metal screen and a surface slick sampler. The underlying waters were also sampled for the determination of the corresponding enrichment factors (EF = [C](microlayer)/[C](underlying water)). The EFs were phase dependent, ranging from 1 to 3 for the dissolved phase and between 4 and 7 for the particulate phase. In order to better assess the performance of the different sampling methods, in terms of phase partitioning, the truly dissolved and colloidal phases were also estimated. Generally, no significant differences were found for the enrichment factors provided by the different methods, due to the observed large variability in concentrations that can be attributed to small-scale coastal processes. However, the metal screen is recommended as the most efficient sampling method for the study of PAHs taking into account the amount of water collected versus time.

[Spontaneous regression of a heart rhabdomyoma in tuberous sclerosis. Apropos of a case]. / Regresión espontánea de un rabdomioma cardíaco en la esclerosis tuberosa. A propósito de un caso.

A case of cardiac rhabdomyoma diagnosed during the neonatal period is presented. The condition remitted spontaneously, as was observed by monitoring its course both clinically and by echocardiography. Surgical treatment of this rare condition should be assessed with care, both because of the risk involved in surgery and because of the possibility of a spontaneous cure in rhabdomyomas, which are usually grouped together, as in our case, in a general picture of tuberous sclerosis.