Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Introduction: Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Material and methods: Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. µ, Æ©, and σ values and margins were obtained. Results: Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors µ, σ and Æ© of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively. Conclusion: Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

In vivo evaluation of skin of children with LC-OCT: An objective assessment.

BACKGROUND: Several non-invasive skin imaging methods have been developed in recent years. Line-field confocal optical coherence tomography (LC-OCT) is one of them, leading to the best compromise in terms of resolution and penetration depth. Skin biopsies are an essential technique in paediatric dermatology, but they are a major stressful event for the child and their parents. Current LC-OCT studies have not been dedicated to a paediatric population. If, however, LC-OCT proves to be helpful in children, it may help guide and decrease a certain number of skin biopsies. OBJECTIVES: (1) To evaluate the feasibility of using LC-OCT in paediatric patients, and (2) to assess the maturation of skin structures in children over time with this method. METHODS: In vivo LC-OCT images were collected on six specific body regions (forehead, forearm, chest, back, dorsum of the hand and palmar surface) and in six age groups (between the ages of 0 and 16 years). RESULTS: In all body areas and age groups assessed, 9 of 10 images were rated as good-to-excellent, the only exception were the images acquired on the palmar surface. LC-OCT allowed visualizing very well the skin structures up to a penetration of 500 µm. We observed that the body regions located on the upper extremities of the body (forearm, dorsum of the hand and palmar surface) showed both a maturation on their structure and differences in thickness with respect to the other regions evaluated. CONCLUSIONS: LC-OCT can easily be used for non-invasive imaging of children's skin and allows to document progressive skin changes in the different age groups. It may be a useful asset for imaging and diagnosing superficial skin disorders and as such reducing the number of invasive procedures while increasing the speed of diagnosis in the paediatric population.

Cambio del modelo asistencial en una unidad de uroginecología de un hospital de tercer nivel: impacto de la pandemia por COVID-19 en la presencialidad / Update of the care model in a urogynaecology unit of a tertiary hospital: impact of the COVID-19 pandemic on face-to-face care

La pandemia por la COVID-19 generó un cambio de forma brusca en la práctica asistencial habitual de nuestra unidad de uroginecología, y a raíz de esta situación se ideó un nuevo modelo asistencial para adaptarnos a la nueva etapa epidemiológica. Se acordó, como eje central del nuevo modelo, la disminución de la presencialidad hospitalaria, ofreciendo la misma calidad asistencial mediante la introducción de la telemedicina.Para conseguir tal fin, se elaboró un modelo con tres tipos de visitas nuevas: primera visita médica telemática, visitas de seguimiento de tratamientos conservadores y farmacológicos telemáticas, y creación de visita pack (pack STUI, el pack posparto y el pack postalta) que incluye visitas y pruebas diagnósticas uroginecológicas que se realizan todas el mismo día.El pack STUI va dirigido a todas las pacientes con síntomas del tracto urinario inferior, asociados o no a prolapso de órganos pélvicos. Consta de dos visitas (enfermería y médica), y dos pruebas diagnósticas avanzadas (urodinamia y ecografía de suelo pélvico).El pack posparto va dirigido a mujeres con síntomas de incontinencia urinaria, incontinencia anal, prolapso y/o alteraciones de la sexualidad tras el parto. También incluye mujeres asintomáticas con antecedente de trauma perineal obstétrico. Consta de una visita médica, una ecografía de suelo pélvico y una visita por la fisioterapeuta.El pack postalta se realiza al mes de la cirugía e incluye dos pruebas (ecografía de suelo pélvico y flujometría) y una visita médica.Los tratamientos de fisioterapia y otras visitas que por motivos médicos lo requirieran, han mantenido su presencialidad.(AU)

The COVID-19 pandemic caused a sudden change in the usual care practice of our urogynaecology unit. Therefore, we designed a new healthcare model to adapt our practice to the epidemiological situation. The central axis of the new model was reduced hospital attendance, offering the same healthcare quality through the introduction of telemedicine.To achieve this aim, we made the following changes: a first telematic medical visit was the first step, telematic monitoring visits for conservative and pharmacological treatments and pack visit. We created the following packs: LUTS, postpartum and post-discharge pack. All packs included visits and diagnostic tests performed on the same day.The LUTS pack is indicated in patients with lower urinary tract symptoms, associated or not with pelvic organ prolapse. It includes two visits (nursing and medical) and two tests (urodynamics and pelvic floor ultrasound).The postpartum pack is indicated in women with symptoms of urinary incontinence, anal incontinence, pelvic organ prolapse and sexual disfunctions after delivery, as well as asymptomatic patients with a history of obstetric perineal trauma. It includes a medical visit, a pelvic floor ultrasound and a visit with the physiotherapist.The post-discharge pack is scheduled a month after the surgery and includes two tests (pelvic floor ultrasound and uroflowmetry) and a medical visit.Some face-to-face visits were maintained, as were physiotherapy treatments and other visits following medical criteria.(AU)

Top-ten papers in pneumonia (2020-2021).

Despite the fact that the last year has been marked by the SARS-CoV-2 pandemic, there have been many articles published on non-COVID pneumonia. Making the selection has not been easy, having based on those articles that we think can bring us some novelty and help in clinical practice. We have divided the selection into seven sections: patient severity, diagnosis, treatment, ventilation, novelties in the guidelines, fungal infection and organ donation.

Aplicabilidad clínica de la ecografía de suelo pélvico en las mujeres con disfunciones miccionales / Clinical applicability of pelvic floor ultrasound in women with urinary dysfunction

Las disfunciones miccionales más frecuentes son la incontinencia urinaria de esfuerzo (IUE), la incontinencia urinaria de urgencia y la dificultad miccional. Son un problema de salud que afecta a la calidad de vida y, a pesar de su alta prevalencia, su etiopatología y fisiopatología sigue sin estar bien establecida. La ecografía de suelo pélvico (ESP) tiene un papel importante para ayudarnos a comprender conceptos de la fisiopatología de estas disfunciones y el manejo clínico de la paciente.La ESP nos permite evaluar la movilidad uretral, la longitud de la uretra y la presencia de embudización del cuello vesical, todos ellos parámetros importantes a considerar, especialmente en aquellas pacientes que se someterán a una cirugía correctora de la IUE. Mediante la ESP evaluamos de forma rutinaria las paredes vesicales y la morfología uretral con el fin de descartar una enfermedad orgánica asociada. La ESP también nos permite evaluar el residuo posmiccional, importante en todas las pacientes con disfunciones miccionales. Finalmente, la ESP es de gran utilidad en la evaluación de las pacientes con antecedente de cirugía antiinconinencia con una banda suburetral libre de tensión (BSLT), permitiendo valorar los parámetros estáticos y dinámicos de la BSLT (en Valsalva), que se correlacionan con la sintomatología descrita por las pacientes.La ESP es una prueba subespecializada que se debe realizar por personal entrenado, y que cada vez va adquiriendo más protagonismo en las unidades de uroginecología. Se espera en un futuro disponer de una terminología estandarizada y de una aplicabilidad más extendida.

Stress urinary incontinence (SUI), urge urinary incontinence, and voiding dysfunction are the most frequent urinary dysfunctions. These dysfunctions affect the patient's quality of life and despite their high prevalence, their aetiopathology and pathophysiology are still not well established. Pelvic floor ultrasound (PFUS) helps us to understand the pathophysiology of these dysfunctions and the clinical evaluation and treatment of patients.PFUS allows us to assess urethral mobility, urethral length, and bladder neck funnelling, all of which are important parameters to be considered in patients undergoing SUI surgery. The evaluation of bladder walls and urethral morphology could be routinely performed by PFUS to assess other pathologies. PFUS also allows us to evaluate the post void residual volume which is especially important in patients with voiding dysfunction. Finally, PFUS is useful in the assessment of the mid urethral slings used for the surgical treatment of SUI. We can evaluate the static and dynamic (with Valsalva) parameters which correlate with the patient's symptoms.PFUS should be performed by trained professionals, and it is expected that in the near future its use will be more extended.

[Update of the care model in a urogynaecology unit of a tertiary hospital: impact of the COVID-19 pandemic on face-to-face care]. / Cambio del modelo asistencial en una unidad de uroginecología de un hospital de tercer nivel: impacto de la pandemia por COVID-19 en la presencialidad.

The COVID-19 pandemic caused a sudden change in the usual care practice of our urogynaecology unit. Therefore, we designed a new healthcare model to adapt our practice to the epidemiological situation. The central axis of the new model was reduced hospital attendance, offering the same healthcare quality through the introduction of telemedicine.To achieve this aim, we made the following changes: a first telematic medical visit was the first step, telematic monitoring visits for conservative and pharmacological treatments and pack visit. We created the following packs: LUTS, postpartum and post-discharge pack. All packs included visits and diagnostic tests performed on the same day.The LUTS pack is indicated in patients with lower urinary tract symptoms, associated or not with pelvic organ prolapse. It includes two visits (nursing and medical) and two tests (urodynamics and pelvic floor ultrasound).The postpartum pack is indicated in women with symptoms of urinary incontinence, anal incontinence, pelvic organ prolapse and sexual disfunctions after delivery, as well as asymptomatic patients with a history of obstetric perineal trauma. It includes a medical visit, a pelvic floor ultrasound and a visit with the physiotherapist.The post-discharge pack is scheduled a month after the surgery and includes two tests (pelvic floor ultrasound and uroflowmetry) and a medical visit.Some face-to-face visits were maintained, as were physiotherapy treatments and other visits following medical criteria.

Brain metastases: Single-dose radiosurgery versus hypofractionated stereotactic radiotherapy: A retrospective study.

BACKGROUND: Radiosurgery is employed for the treatment of brain metastases. The aim of this study is to evaluate the efficacy and tolerability of single-dose radiosurgery (SRS) compared to hypofractionated stereotactic radiotherapy (hFSRT). MATERIALS AND METHODS: Between 2004 and 2018, we analyzed treatments of 97 patients with 135 brain metastases. Fifty-six patients were treated with SRS, and 41 patients were treated with hFSRT. Median dose was 16 Gy (12-20 Gy) for the SRS group and 30 Gy in 5-6 fractions for the hFSRT group. hFSRT was used for larger lesions and lesions located near critical structures. Kaplan-Meier curves were constructed for overall survival (OS) and local control (LC). RESULTS: Median age was 64 years (range, 32-89 years). Median survival was 10 months (1-68 months). With a median follow-up of 10 months, no significant differences in OS between groups were found (P=0.21). LC for all patients was 67%. Local progression-free survival (LPFS) at 6 months and 1 year was 71% and 60% for the SRS group, respectively, and 80% and 69% for the hFSRT group, respectively (P=0.93). Although hFSRT was used for larger lesions and lesions in adverse locations, LPFS was not inferior compared to lesions treated with SRS. We observed acute toxicity grade 1-2 in 25 patients (25.8%). Late complications were observed in 11 patients (11.3%). Acute and late toxicity was similar in the SRS- and hFSRT-treated patients (P=0.63 and P=0.11, respectively). Brain recurrence occurred in 37.5% and 14.6% in the hFSRT and SRS group, respectively (P=0.06). CONCLUSIONS: Since patients treated with hFSRT exhibited similar survival and LPFS rates without differences in toxicity compared to those treated with SRS, hFSRT can be beneficial, particularly for patients with brain metastases. RELEVANCE FOR PATIENTS: Hypofractionated schemes in stereotactic radiosurgery offers treatment alternatives to patients with large lesions or lesions near critical structures.

Cómo la pandemia por COVID-19 ha cambiado la forma de atender a las pacientes en una unidad de uroginecología / How did COVID-19 pandemic change the way we attend the patients in an urogynaecological unit

La actual pandemia ocasionada por el SARS-coronavirus tipo 2 ha generado, en pocas semanas, cambios importantes en el funcionamiento del sistema sanitario y la forma en cómo se realiza la atención a las pacientes. La patología uroginecológica afecta a la calidad de vida, pero sin riesgo vital en la mayoría de casos, por lo que suele ser demorable. Además, afecta a un alto porcentaje de mujeres > 65 años (población de riesgo ante la infección por COVID-19). En este manuscrito se resume la evidencia que existe sobre la efectividad de la telemedicina aplicada en las disfunciones de suelo pélvico, así como recomendaciones de las sociedades científicas uroginecológicas durante el estado de alarma. Describimos el abordaje de las disfunciones de suelo pélvico durante la pandemia por COVID-19 y una propuesta de cómo organizar las agendas para el diagnóstico (visitas y pruebas diagnósticas) y tratamiento (conservador, farmacológico y la cirugía) en el período interpandemia y en el futuro

The current SARS-coronavirus type 2 pandemic caused, in few weeks, important changes in the health system organization and in the way we attend the patients. Urogynaecological diseases affect quality of life, but without life risk in most cases, so it is possible to delay. Moreover, urogynaecological diseases affect mostly women over 65 years old (a high risk population for contracting COVID-19). In this manuscript we summarise the current evidence about telemedicine efectivity to manage to pelvic floor dysfunctions and, in addition, the recommendations of Urogynaecological scientific societies during state of alarm. We describe the management of the different pelvic floor dysfunctions during COVID-19 pandemic and a proposal to organize the urogynaecological services to diagnose (visits and diagnostic investigations) and to treat (conservative, pharmacological or surgery) in the interpandemic period and in the future

[How did COVID-19 pandemic change the way we attend the patients in an urogynaecological unit]. / Cómo la pandemia por COVID-19 ha cambiado la forma de atender a las pacientes en una unidad de uroginecología.

The current SARS-coronavirus type 2 pandemic caused, in few weeks, important changes in the health system organization and in the way we attend the patients. Urogynaecological diseases affect quality of life, but without life risk in most cases, so it is possible to delay. Moreover, urogynaecological diseases affect mostly women over 65 years old (a high risk population for contracting COVID-19). In this manuscript we summarise the current evidence about telemedicine efectivity to manage to pelvic floor dysfunctions and, in addition, the recommendations of Urogynaecological scientific societies during state of alarm. We describe the management of the different pelvic floor dysfunctions during COVID-19 pandemic and a proposal to organize the urogynaecological services to diagnose (visits and diagnostic investigations) and to treat (conservative, pharmacological or surgery) in the interpandemic period and in the future.

[Use of single-electrode EEG in the evaluation of attention-deficit/hyperactivity disorder]. / Empleo del electroencefalograma de un solo electrodo en la evaluación del trastorno por déficit de atención/hiperactividad.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) maintains a diagnosis based on behavioral data despite its involvement in neuropsychophysiological models. The monopolar electroencephalography (EEG) record focused on differentiating children with ADHD versus controls based on a higher theta/beta ratio has been proposed as an alternative to objectify the diagnosis and guide neurofeedback-based intervention, but its results have been controversial. AIM: To analyze the viability of a single electrode to detect differences in the main cerebral rhythms and especially in theta/beta ratio, in children diagnosed with ADHD, analyzing the differences by subtype, age, sex and type of experimental task. PATIENTS AND METHODS: 92 children (range: 7-13 years) diagnosed with ADHD were evaluated in a monopolar EEG record on four experimental tasks (rest, reading, active listening and copying a figure). Seven measures on slow and fast EEG rhythms were obtained, plus theta/beta ratio. RESULTS: There were no differences by ADHD subtypes. The task of greatest cognitive demand obtained the highest wave amplitudes. Smaller participants and boys presented higher amplitudes in slow waves and in theta/beta ratio in all the experimental tasks, showing a greater tendency to attentional regulation problems. CONCLUSION: Monopolar record and theta/beta ratio are a viable alternative in the clinical setting to complement the evaluation of ADHD.

TITLE: Empleo del electroencefalograma de un solo electrodo en la evaluación del trastorno por déficit de atención/hiperactividad.Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) mantiene un diagnóstico basado en datos conductuales a pesar de su implicación en modelos neuropsicofisiológicos. El registro del electroencefalograma (EEG) monopolar centrado en diferenciar a los niños con TDAH frente a los controles en función de una mayor ratio theta/beta se ha propuesto desde hace tiempo como una alternativa para objetivar el diagnóstico y guiar la intervención basada en neurofeedback, pero sus resultados han resultado controvertidos. Objetivo. Analizar la viabilidad de un único electrodo para detectar diferencias en los principales ritmos cerebrales, y especialmente en la ratio theta/beta, en niños con diagnóstico de TDAH, analizando las diferencias por subtipo, edad, sexo y tarea. Pacientes y métodos. Se evaluó a 92 niños (rango: 7-13 años) con diagnóstico de TDAH en un registro de EEG monopolar sobre cuatro tareas (reposo, lectura, escucha activa y copiar una figura). Se obtuvieron siete medidas basadas en ritmos EEG lentos y rápidos, más la ratio theta/beta. Resultados. No hubo diferencias por subtipos de TDAH. La tarea de mayor demanda cognitiva obtuvo en general las amplitudes de onda más elevadas. Los participantes más pequeños y los varones presentaron en general una ratio theta/beta y amplitudes en las ondas lentas más elevadas en todas las tareas investigadas, y mostraron una mayor tendencia a problemas de regulación atencional. Conclusión. El registro monopolar y la ratio theta/beta son una alternativa viable en el ámbito clínico, al menos para complementar la evaluación del TDAH.

Effects of the antimicrobial peptide protegrine 1 on sperm viability and bacterial load of boar seminal doses.

The presence of bacteria adversely affects boar sperm quality of seminal doses intended for artificial insemination. Currently, the most common measure to prevent bacteriospermia is the addition of antibiotics in semen extenders; however, mounting evidence shows that microbial resistance exists. A promising alternative to replace antibiotics are antimicrobial peptides. In this study, the effects of the antimicrobial peptide protegrine 1 (PG1) on the sperm viability and bacterial load of boar seminal doses were evaluated. Three different concentrations of PG1 (2.5, 25 and 100 µg/ml) were tested over a storing period of 10 days at 17°C. Sperm viability was analysed by fluorescence microscopy (SYBR14/propidium iodide), and bacterial load was assessed by plating 100 µl of each sample in Luria-Bertani medium and incubated at 37°C for 72 hr under aerobic conditions. Protegrine 1 was effective in controlling the bacterial load in all the assessed concentrations (p < .05), reaching the lowest values at the highest concentrations of the antimicrobial peptide. Nevertheless, sperm viability was significantly (p < .05) reduced by all tested concentrations of this peptide, the most cytotoxic effects being observed at the highest PG1 concentrations. Despite these results, the use of PG1 as an alternative to antibiotics cannot be totally discarded, as further studies using the truncated form of this peptide are needed.

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81µgcm-2h-1 whereas the highest iontophoretic transport was 46.4±3.6µgcm-2h-1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.

Topical delivery of diclofenac into and across equine skin from a novel liquid diclofenac epolamine formulation.

The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass® (1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)]. Cumulative permeation of diclofenac in Groups 1 and 2 after 24 h using diclofenac sodium solution was 1.91 ± 0.27 and 1.76 ± 0.34 µg/cm2 , respectively. The values for Surpass® and DIC-EP were 3.2 ± 0.8/3.3 ± 0.7 µg/cm2 and 230 ± 59/89.2 ± 32.5 µg/cm2 , respectively. Thus, diclofenac permeation from DIC-EP was significantly greater and appeared to show an age-dependent effect. Mathematical modelling showed that the DIC-EP formulation significantly increased diclofenac partitioning into the skin and a linear correlation was observed between steady-state flux and the partition parameter. Greater skin deposition of diclofenac was also observed with DIC-EP. These preliminary results suggest that the DIC-EP formulation may be effective in treating inflammatory conditions in horses.

Two-phase fluid flow in geometric packing.

We investigate how a plug of obstacles inside a two-dimensional channel affects the drainage of high viscous fluid (oil) when the channel is invaded by a less viscous fluid (water). The plug consists of an Apollonian packing with, at most, 17 circles of different sizes, which is intended to model an inhomogeneous porous region. The work aims to quantify the amount of retained oil in the region where the flow is influenced by the packing. The investigation, carried out with the help of the computational fluid dynamics package ANSYS-FLUENT, is based on the integration of the complete set of equations of motion. The study considers the effect of both the injection speed and the number and size of obstacles, which directly affects the porosity of the system. The results indicate a complex dependence in the fraction of retained oil on the velocity and geometric parameters. The regions where the oil remains trapped is very sensitive to the number of circles and their size, which influence in different ways the porosity of the system. Nevertheless, at low values of Reynolds and capillary numbers Re<4 and n(c)≃10(-5), the overall expected result that the volume fraction of oil retained decreases with increasing porosity is recovered. A direct relationship between the injection speed and the fraction of oil is also obtained.

Development of antimigraine transdermal delivery systems of pizotifen malate.

The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate.

Comparative analysis of boar seminal plasma proteome from different freezability ejaculates and identification of Fibronectin 1 as sperm freezability marker.

Variation in boar sperm freezability (i.e. capacity to withstand cryopreservation) between ejaculates is a limitation largely reported in the literature. Prediction of sperm freezability and classification of boar ejaculates into good (GFEs) and poor freezability ejaculates (PFEs) before cryopreservation takes place may increase the use of frozen-thawed spermatozoa. While markers of boar sperm freezability have been found from sperm cell extracts, little attention has been paid to seminal plasma. On this basis, the present study compared the fresh seminal plasma proteome of 9 GFEs and 9 PFEs through two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography mass spectrometry (LC-MS/MS). The ejaculates were previously classified as GFE or PFE upon their sperm viability and progressive motility assessments at 30 and 240 min post thawing. From a total of 51 spots, four were found to significantly (p < 0.05) differ between GFEs and PFEs, and two were identified as fibronectin-1 (FN1) and glutathione peroxidase 5 (GPX5). These two potential markers were further studied by western blot and correlation analysis between protein relative abundances in fresh seminal plasma and regression factors from principal component analyses (PCA) run using post-thawing sperm quality parameters. Results confirmed that FN1 is a reliable marker of boar sperm freezability, because GFEs presented significantly (p < 0.05) higher FN1-amounts than PFEs and FN1 was found to be correlated with the first PCA component at 240 min post thawing. In contrast, GPX5 was not validated as a boar sperm freezability marker. We can thus conclude that levels of FN1 in fresh seminal plasma from boar semen may be used as a sperm freezability marker, thereby facilitating the use of frozen-thawed boar spermatozoa.

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

BACKGROUND: A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. OBJECTIVE: To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. METHODS: In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. RESULTS: While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. CONCLUSIONS: RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies.

Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity.

The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5 mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations.

HPLC-UV analytical method for determination of pizotifen after in vitro transdermal diffusion studies.

Pizotifen malate is an antihistamine and serotonin inhibitor used in the preventive treatment of migraine and eating disorders. A simple, rapid, accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection was validated for the quantitative analysis of pizotifen malate in samples from in vitro transdermal diffusion studies. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantification and robustness. Drug stability in the solution was also determined under different conditions. Separation was carried out using a 250 × 4.0 mm Kromasil(®) C(18) column at room temperature. The detector response, fitted at 254 nm, was found to be linear in a concentration range between 0.24 and 24.0 µg/mL. The limit of detection was 0.02 µg/mL and the limit of quantification was 0.07 µg/mL. Finally, in vitro transdermal diffusion of pizotifen malate was characterized using the validated HPLC method.