Diagnosis and treatment of disorders of intracranial pressure: consensus statement of the Spanish Society of Neurology's Headache Study Group.

Primary intracranial pressure disorders include idiopathic intracranial hypertension and spontaneous intracranial hypotension. Remarkable advances have been made in the diagnosis and treatment of these 2entities in recent years. Therefore, the Spanish Society of Neurology's Headache Study Group (GECSEN) deemed it necessary to prepare this consensus statement, including diagnostic and therapeutic algorithms to facilitate and improve the management of these disorders in clinical practice. This document was created by a committee of experts belonging to GECSEN, and is based on a systematic review of the literature, incorporating the experience of the participants, and establishes practical recommendations with levels of evidence and grades of recommendation.

[New therapeutic era for migraine attacks with recently approved monoclonal antibodies, ditans and gepants]. / Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant). Furthermore, eptinezumab, which has been approved for the preventive treatment of migraine in adults, has also been used for migraine attacks. This manuscript reviews the efficacy and safety results of the new drugs for migraines that will soon be on the market.

TITLE: Nueva era terapéutica para el ataque de migraña con los recientemente aprobados anticuerpos monoclonales, ditanes y gepantes.El tratamiento de los ataques de migraña se aconseja en todos los pacientes, utilizando antiinflamatorios no esteroideos cuando el dolor es leve y triptanes cuando la intensidad del dolor es moderada-grave. Sin embargo, la efectividad de estos fármacos es modesta, un porcentaje elevado de pacientes presenta efectos secundarios y los triptanes están contraindicados en las personas con antecedentes de ictus, cardiopatía isquémica o hipertensión mal controlada. Por tanto, es imprescindible disponer de nuevas alternativas terapéuticas. En los últimos años han ido apareciendo nuevos fármacos para los ataques de migraña, entre los que destacan los ditanes (lasmiditán) y los gepantes (ubrogepant y rimegepant). Por otro lado, el eptinezumab, que ha sido aprobado para el tratamiento preventivo de la migraña en adultos, se ha utilizado también para los ataques de migraña. En este manuscrito se revisan los resultados de eficacia y seguridad de los nuevos fármacos para los ataques de migraña que se comercializarán próximamente.

Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.

Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.

T cell suppression in vitro during Toxoplasma gondii infection is the result of IL-2 competition between Tregs and T cells leading to death of proliferating T cells.

A reduced proliferation to T cell mitogens is observed in vitro in murine cells isolated during the acute phase of Toxoplasma gondii infection. Foxp3(+) regulatory T cells (Tregs) mediate this suppression, which is interleukin (IL)-2 dependent. In this work, we analysed the mechanism of this Treg-mediated suppression. We found that removal of antigen-presenting cells (APC) from spleen cells from infected mice did not modify suppression but further elimination of Tregs led to a restored proliferation, demonstrating that Tregs mediate suppression in the absence of APC. Production of IL-2 by T cells from infected animals was abolished but partially restored when Tregs were removed. However, IL-2 levels and T cell proliferation were restored when Tregs and T cells were separated by transwells, indicating that Tregs require close proximity with T cells to induce suppression. Tregs from infected mice were able to reduce proliferation of CTLL-2 cells in the classical IL-2 bioassay, strongly suggesting that Tregs compete with T cells for IL-2. We found that T cells from infected mice died after a few rounds of division in vitro, but addition of recombinant IL-2 or removal of Tregs abolished this effect. Our results showed that suppression of T cell proliferation during acute Toxoplasma gondii infection is the result of death of proliferating T cells by Treg-mediated IL-2 competition. Thus, immunosuppression is due to death of proliferating T cells as a consequence of low IL-2 availability.

Protocolo modificado de la terapia del movimiento inducido por restricción para un hospital de atención a crónicos y larga estancia / Modified protocol of constraint-induced movement therapy for a chronic and long term care hospital

Introducción. La terapia del movimiento inducido por restricción es una de las pocas terapias de rehabilitación del miembro superior que ha demostrado científicamente que tiene un impacto en las actividades de la vida diaria. El objetivo del ensayo clínico aleatorizado es comprobar si la modificación del protocolo original de la terapia del movimiento inducido por restricción mejora la elegibilidad del protocolo original y mantiene los beneficios del mismo. Material y método. Se realiza un estudio comparativo en una muestra de 32 pacientes que han sufrido un accidente cerebrovascular, divididos de manera aleatoria en un grupo experimental y otro control, para determinar si una modificación del protocolo original de la terapia del movimiento inducido por restricción tiene un impacto significativo en la mejora de las actividades de la vida diaria dentro del tratamiento global de pacientes ingresados en un Hospital de atención a crónicos y larga estancia, el Hospital «Pare Jofré» de la ciudad de Valencia. La técnica es comparada con el tratamiento tradicional de terapia ocupacional. Resultados. Se consigue aumentar la elegibilidad de un 1,6%, hasta un 26,22%. Se observa una mejora funcional en las actividades de la vida diaria por el impacto de la técnica dentro del período ingreso-alta con significación estadística (U de Mann-Whitney 0,001) y una diferencia significativa en los niveles de dependencia entre el grupo experimental y el grupo control, observándose que los pacientes que reciben la técnica tienen menores niveles de dependencia (Chi-cuadrado 0,038) y diferencias estadísticamente significativas para actividades de la vida diaria como la alimentación, el vestido, el aseo personal, la ducha, el uso del retrete las transferencias y el desplazamiento, por lo que podemos decir que se mantienen los beneficios del protocolo original. Conclusión. El protocolo modificado mejora la elegibilidad de los pacientes, así como los resultados de los pacientes en actividades de la vida diaria, tanto en alimentación, vestido, higiene, baño, uso del retrete y transferencias (AU)

Introduction. Constraint-induced movement therapy is one of the few therapies for upper limb rehabilitation that has been scientifically proven to have an impact on daily life activities. The purpose of this clinical trial is check whether the modification of the original protocol of constraint- induced movement therapy improves the eligibility restrictions of the original protocol and maintains the benefits. Material and methods. We performed a comparative study on a sample of 32 patients who had suffered a stroke. They were randomly divided into an experimental group and a control group to determine if a modification of the original protocol of constraint-induced movement therapy has a significant impact on improvement in daily living activities within the overall treatment of patients admitted to a chronic care, long stay, hospital, that is, the Hospital “Pare Jofre” of the city of Valencia. The technique was compared with the traditional treatment of occupational therapy. Results. Eligibility is increased from 1.6% to 26.22%. We observed functional improvement in activities of daily living with statistical significance (Mann-Whitney U Test: 0.001) and a significant difference in levels of dependence between the experimental and control group. It has been observed that patients receiving the technique have lower levels of dependency (Chi-square 0.038) and statistically significant differences for activities of daily life, such as eating, dressing, personal hygiene, showering, use of toilet, transfers and movements from one place to another, so we can say that the benefits of the original protocol are maintained. Conclusions. Eligibility is increased with this modified protocol and it has better results in activities of daily living, such as feeding, dressing, hygiene, bathroom, use of the toilet and transfers (AU)

Gonadotrophin levels and morphological testicular features in rats after different doses of the phytoestrogen coumestrol.

INTRODUCTION: Phytoestrogens are a wide variety of chemical compounds, mainly isoflavonoids, from a vegetable source. Their name makes reference to their ability to induce estrogenic responses in mammals. Coumestrol is a phytoestrogen that can be found in high concentrations in the dietary elements of cattle. Some endocrine alterations have been reported for cows and ewes after ingestion of vegetables with high concentrations of coumestrol. However, these studies have been made mainly in females. OBJECTIVE: To analyze some features of the masculine endocrine response in rats after several doses of the phytoestrogen coumestrol. DESIGN: Adult male rats were injected with several doses of coumestrol. Plasma gonadotrophins (LH/FSH) and testosterone levels were assessed. In addition, morphology of the testicles was analyzed. SETTING: Experiments were done in the facilities of the neurosciences area at the University. RESULTS: No significant changes were observed in gonadotrophin levels after the administration of coumestrol. Testosterone levels showed a significant decrease with the higher doses. Morphological analysis showed an inhibitory effect on spermatogenesis expressed mainly in the right testicle. Testicular volume decreased and the tubular area increased significantly after coumestrol treatment. CONCLUSIONS: These results suggest that the endocrine effect of coumestrol is mainly expressed in peripheral targets in male rats. In addition, the possible mediation of estrogen beta receptors is discussed.

The macroinfauna of the Galician sandy beaches (NW Spain) affected by the Prestige oil-spill.

Eighteen sandy beaches were sampled along the 1659 km of the Galician coast (NW Spain) six months after the Prestige oil-spill to study the impact of the fuel and the clean-up activities on the macroinfauna community. A transect was extended at each beach, from above the drift line to below the swash line at five sampled levels; at each level six 0.05 m2 replicates were taken to a depth of 30 cm and sieved through a 1mm mesh, and the organisms collected and preserved. Results were compared with previous data obtained using the same procedures. The macroinfauna was numerically dominated by the amphipod Pontocrates arenarius, the isopod genus Eurydice, the polychaete Scolelepis squamata, and the amphipod Talitrus saltator. As a result of the Prestige oil-spill and the clean-up activities, beach populations were reduced, with Eurydice and S. squamata as the most affected taxa.

Risk factors and the prevalence of leptospirosis infection in a rural community of Chiapas, Mexico.

A cross-sectional study was conducted in Mapastepec, a rural community of the southern state of Chiapas, Mexico. The overall prevalence of leptospirosis infection in 1169 subjects was 37.7% [95% confidence intervals (95% CI) 34.9-40.5]. The main risk factors related to leptospirosis infection were flooding, mainly if subjects had a skin cut or abrasion [odds ratio (OR) 4.2; 95% CI 3.1-5.7], having domestic animals, either dogs and/or cats (OR 1.3; 95% CI 0.96-1.8) or cattle and/or pigs (OR 1.9; 95% CI 1.3-2.7), contact with animal excreta with no protection and with a skin cut or abrasion (OR 2.3; 95% CI 1.1-4.6). Those subjects with a dengue infection in the previous year had also an excess risk (OR 1.4; 95% CI 0.9-2.0). Mapastepec is a previously unknown area with high endemicity. Specific preventive measures should be adopted to prevent any contact with infected animals, and animal immunization should also be implemented. There is need of an epidemiological surveillance system to allow proper diagnosis.

TC helicoidal del estómago: diferenciación entre patología benigna y maligna y estadificación del carcinoma gástrico / Helical CT of the sto mach: differentiation between benign and malignat patholo gies, together with the staging of gastric carcinoma

Objetivos: valorar la capacidad de la HidroTC helicoidal para diferenciar la patología gástrica benigna de la maligna y, medir su utilidad en la estadificación del carcinoma gástrico. Pacientes y diseño: realizamos un estudio transversal de evaluación de la eficacia diagnóstica de la TC, con recogida prospectiva de los pacientes. Estudiamos a 92 pacientes con sospecha clínica de patología gástrica con TC helicoidal con contraste (TCHC), con agua como contraste oral y contraste yodado i.v. De acuerdo con trabajos previos consideramos como normal el estómago cuando el grosor de su pared es menor o igual a 6 mm, presenta una apariencia multicapeada y se realza homogéneamente con el contraste i.v. Se diagnosticó como tumor maligno, si existía un grosor de pared aumentado, marcado realce con el contraste y pérdida del patrón multicapa normal. Se clasificó como gastritis un engrosamiento parietal, sin excesivo realce y sin pérdida del patrón en capas. Las masas con bordes lisos, crecimiento intraluminal y morfología redondeada fueron diagnosticadas como tumores submucosos. Los resultados de nuestros 92 estudios fueron cotejados, en la totalidad de los casos, con los hallazgos del estudio endoscópico y en los 52 pacientes intervenidos con los hallazgos quirúrgicos. Resultados: en 12 de los 92 pacientes estudiados con TCHC no se objetivó patología gástrica en la TC ni en la endoscopia. De los 80 casos patológicos diagnosticamos en TC 29 como patología benigna (19 se confirmaron con histología) y en 51 patología maligna (con confirmación histológica en 49).Obtuvimos una sensibilidad del 81,7 por ciento en el diagnóstico de patología maligna y una especificidad del 90 por ciento, con un VPP del 96 por ciento y VPN del 62 por ciento. Respecto a la estadificación TNM (en relación con la clasificación TNM de 1997) la fiabilidad diagnóstica obtenida fue del 56 por ciento para T y N, y del 87 por ciento para M. Conclusiones: la hidroTC helicoidal permite diagnosticar el carcinoma gástrico avanzado. Su utilidad fundamental es la valoración de la enfermedad neoplásica metastásica. También se ha demostrado útil en el diagnóstico de patologías benignas. No es un buen método de cribado para el diagnóstico del carcinoma gástrico (AU)

Differentiation of the raw material of the Iberian pig meat industry based on the use of amplified fragment length polymorphism.

The present study is the first step of the development of a new analytical technique to discriminate the genotypes of purebred Iberian and crossbred Iberian×Duroc pigs. A DNA test of breed identity has clear advantages for the protection of the brand name of high-prized products of purebred Iberian pigs. Amplified fragment length polymorphism procedure was used to analyze the genomic DNA samples of 77 Duroc and 80 Iberian pigs from the most representative populations. Thirteen primer combinations produced 588 amplified fragments. A total number of 139 fragments were polymorphic and 14 out of them were detected in Duroc and never in Iberian pigs. A panel of the nine most frequent markers allows the discrimination between purebred and crossbred animals. The values of the probability of exclusion of the pure Iberian origin (P(EC)) were 0.97 and 0.78, for crossbred individuals with 50 or 25% of Duroc genes, respectively.

Helical CT of the stomach: differentiation between benign and malignant pathologies, together with the staging of gastric carcinoma.

OBJECTIVES: To evaluate the capacity of Helical Hydro-CT to differentiate between benign and malignant gastric pathologies, and also to measure its usefulness in the staging of gastric carcinoma. PATIENTS AND DESIGN: We perform a cross-sectional study to evaluate the diagnostic efficacy of CT, including patients prospectively. We study 92 patients with a clinical suspicion of gastric pathology using helical CT with a contrast agent (HCTC), water being the oral contrast agent, and i.v. iodine contrast. According to the findings of previous works, we considered stomachs to be normal when the thickness of their wall was less than or equal to 6 mm, with a multilayered appearance that stands out homogeneously with the i.v. contrast. A malignant tumour was diagnosed if the thickness of the wall was greater, together with strong marking by the contrast agent and loss of the normal multilayered pattern. Parietal thickening was classified as gastritis if there was no excessive marking and no loss of the layered pattern. Masses with smooth borders, intraluminal growth and a rounded morphology were diagnosed as sub-mucosal tumours. The results of our 92 studies were compared in all cases with the findings of endoscopic studies, while in the 52 patients treated with surgery they were compared against surgical findings. RESULTS: In 12 of the 92 patients studied using HCTC no gastric pathology was observed by CT or endoscopy. Of the 80 pathological cases CT was used to diagnose 29 as benign pathology, 19 of which were confirmed as such by histology, and 51 cases as malignant pathology, of which 49 were confirmed by histology. We obtained a sensitivity of 81.7% in the diagnosis of malignant pathology and a specificity of 90%, with a PPV of 96% and a NPV of 62%. Regarding TNM staging (in comparison with the 1997 TNM classification), the diagnostic reliability obtained amounted to 56% for T and N, and 87% for M. CONCLUSIONS: Helical hydro CT makes it possible to diagnose advanced gastric carcinoma. Its usefulness basically lies in the evaluation of metastatic neoplastic disease. It has also been shown to be useful in the diagnosis of benign pathologies. It is not a good screening method for the diagnosis of gastric carcinoma.

Pseudoartrosis atrófica con defecto óseo en secuelas de fracturas de la diáfisis humeral: tratamiento con placa en onda más colocación de autoinjertos óseos / Atrophic ununited diaphyseal fractures of the humerus with a bony defect: treatment using a wave-plate

Entre 1993 y 2000 fueron tratados en el Departamento de Ortopedia y Traumatología del Hospital Clínica San Rafael y en la practica privada del co-autor, 22 pacientes con pseudoartrosis atrófica de húmero con defecto óseo, utilizando placa en puente con moldeo en onda y autoinjerto de hueso córtico-esponjoso. En tres casos se agregó un autoinjerto estructural de peroné. La longitud promedio del defecto óseo fue de 2,2 cm (1-7 cm). En 18 pacientes (81 por ciento) se logró un seguimiento clínico y radiológico de 10 meses (5-36 meses); con este único procedimiento consolidaron 16 casos (89 por ciento) y 2 casos (11 por ciento) requirieron una revisión con nueva colocación de injertos y osteosíntesis. Los resultados sugieren que en presencia de un adecuado cubrimiento muscular, la aplicación de una placa en onda con injertos óseos autólogos, representa una buena alternativa para el tratamiento de la pseudoartrosis atrófica compleja de húmero

Pattern- and growth-linked cell cycles in Drosophila development.

During Drosophila development the cell cycle is subject to diverse regulatory inputs. In embryos, cells divide in stereotypic patterns that correspond to the cell fate map. There is little cell growth during this period, and cell proliferation is regulated at G2/M transitions by patterned transcription of the Cdk1-activator, Cdc25/String. The string locus senses pattern information via a > 40 kb cis-regulatory region composed of many cell-type specific transcriptional enhancers. Later, in differentiated larval tissues, the cell cycle responds to nutrition via mechanisms that sense cellular growth. These larval cell cycles lack mitoses altogether, and are regulated at G/S transitions. Cells in developing imaginal discs exhibit a cycle that is regulated at both G1/S and G2/M transitions. G2/M progression in disc cells is regulated, as in the embryo, by string transcription and is thus influenced by the many transcription factors that interact with string's 'pattern-sensing' control region. G1/S progression in disc cells is controlled, at least in part, by factors that regulate cell growth such as Myc, Ras and phosphatidylinositol-3-kinase. Thus G1/S progression appears to be growth-coupled, much as in the larval endocycles. The dual control mechanism used by imaginal disc cells allows integration of diverse inputs which operate in both cell specification and cell metabolism.

Analysis of the individual role of the TCRzeta chain in transgenic mice after conditional activation with chemical inducers of dimerization.

Signaling through the TCR/CD3 complex plays a critical role in T-cell development and activation. Gene-targeted mice lacking particular components of this complex show arrested T-cell development in the thymus. As all TCR/CD3 components are required for efficient surface expression of the complex, it is difficult to assess the specific signaling role of each receptor component. To overcome this problem, we designed a strategy to examine the specific role(s) of individual receptor chains. A chimeric protein, containing binding domains for chemical inducers of dimerization fused to the cytoplasmic tail of TCRzeta, was generated. Activation of the chimeric receptor after stimulation with chemical dimerizers in Jurkat cells showed tyrosine phosphorylation of the TCRzeta chain chimera, recruitment of phosphorylated Zap70, and generation of NFAT in a reporter assay. Analysis of thymocytes from transgenic mice expressing this chimeric receptor showed that intracytoplasmic crosslinking of the chimera induced tyrosine phosphorylation of the protein, as well as a slow and very weak calcium mobilization response. However, this signaling did not lead to increased expression of activation markers, T-cell proliferation, or apoptosis. In addition, stimulation of thymocytes in suspension or in fetal thymic organ cultures with chemical inducers of dimerization did not lead to alterations in positive or negative selection. We conclude that signaling through the TCRzeta chain alone is not sufficient to generate downstream events leading to full T-cell activation or thymocyte selection; instead, additional CD3 components must be required to induce a functional response in primary thymocytes and peripheral T cells.

Simple and rapid determination of carboplatin in plasma by high-performance liquid chromatography. Error pattern and application to clinical pharmacokinetic studies.

Carboplatin is an antitumor agent widely employed in cancer chemotherapy. A specific and selective method for the determination of carboplatin in human plasma and its applications to pharmacokinetic investigations is described. One ultrafiltration step, through a Centrifree micropartition system (Amicon) at 2000 g for 10 min, is the only requirement as sample treatment. The resulting solution is injected into an Inertsil ODS-2 (5 microm, 25 cm x 4.6 mm I.D.) analytical column. The mobile phase consisted of 0.1 M potassium dihydrogenphosphate with 1 mM dipotassium edetate adjusted to a pH between 3 and 3.5. The limit of quantitation was 1 mg/l. The method showed good recovery (100.68+/-5.49%) and precision: the within-day relative standard deviation (RSD) for carboplatin (3-350 mg/l) was 2.07% and the between-day RSD for carboplatin, in the previously described range, was 1.31%. We determined the assay error pattern for proper weighting of serum level data in pharmacokinetic models. The selectivity (discrimination between the parent drug and platinum-containing species such as carboplatin metabolites), simplicity and speed of this assay for free carboplatin quantitation should facilitate pharmacokinetic investigations and therapeutic drug monitoring.

Simple and rapid determination of irinotecan and its metabolite SN-38 in plasma by high-performance liquid-chromatography: application to clinical pharmacokinetic studies.

Irinotecan (CPT-11) is an anticancer agent widely employed in the treatment of colorectal carcinoma. A simple, rapid and sensitive high-performance liquid chromatographic method for the simultaneous determination of CPT-11 and its metabolite SN-38 in plasma, and their preliminary clinical pharmacokinetics are described. Both deproteinisation of plasma specimens (100 microl) and addition of the internal standard, camptothecin (CPT), are achieved by incorporating to samples 100 microl of a solution of CPT (1 microg/ml) in acetonitrile-1 mM orthophosphoric acid (90:10); 200 microl of this acidified acetonitrile solution, drug-free, is also added to accomplish complete deproteinisation: this procedure reduces sample preparation time to a minimum. After deproteinisation, samples are treated with potassium dihydrogenphosphate (0.1 M) and injected into a Nucleosil C18 (5 microm, 250 x 4.0 mm) column. Mobile phase consists of potassium dihydrogenphosphate (0.1 M)-acetonitrile (67:33), at a flow-rate of 1 ml/min. CPT-11, SN-38 and CPT are detected by fluorescence with excitation wavelength set at 228 nm and emission wavelengths of CPT-11, SN-38 and CPT fixed, respectively, at 450, 543 and 433 nm. The limits of quantitation for CPT-11 and SN-38 are 1.0 and 0.5 ng/ml, respectively. This method shows good precision: the within day relative standard deviation (RSD) for CPT-11 (1-10000 ng/ml) is 5.17% (range 2.15-8.27%) and for SN-38 (0.5-400 ng/ml) is 4.33% (1.32-7.78%); the between-day RSDs for CPT-11 and SN-38, in the previously described ranges, are 6.82% (5.03-10.8%) and 4.94% (2.09-9.30%), respectively. Using this assay, plasma pharmacokinetics of CPT-11, SN-38 and its glucuronidated form, SN-38G, have been determined in one patient receiving 200 mg/m2 of CPT-11 as a 90 min intravenous infusion. The peak plasma concentration of CPT-11 at the end of the infusion is 3800 ng/ml. Plasma decay is biphasic with a terminal half-life of 11.6 h. The volume of distribution at steady state (Vss) is 203 l/m2, and the total body clearance (Cl) is 14.8 l/h x m2. The maximum concentrations of SN-38 and SN-38G reach 28.9 and 151 ng/ml, respectively.

Characterization of Iberian pig genotypes using AFLP markers.

The use of the AFLP (amplified fragment length polymorphism) technique for the characterization of highly inbred Iberian pig breed genotypes and the detection of strain-specific polymorphisms is demonstrated. Twelve different primer combinations were used on individual DNA samples from animals belonging to two black hairless Iberian pig strains, Guadyerbas and Coronado. These amplification reactions allowed the detection of more than 1700 amplification products of which 26 were identified as strain-specific markers, present in all individuals of one strain and absent in the other. Comparison of male and female amplification products within one strain also allowed the identification of 8 male-specific amplified bands. AFLP showed a great power of marker detection due to a high multiplex ratio and high reproducibility. Comparison of similarity and co-ancestry coefficient matrices also showed the usefulness of AFLP markers to estimate genetic relationships between individuals pigs.

Actualización en el tratamiento de la pediculosis, sarna y leishmaniasis / Treatment review in pediculosis scabies and leishmaniasis

Realizamos una revisión de los principales agentes utilizados en el tratamiento de la pediculosis, sarna y leishmaniasis.Actualmente constituyen el tratamiento de elección tanto para la pediculosis como para la sarna las piretrinas y sus derivados sintéticos (permetrina tópica) y además para la escabiosis la ivermectina oral (200 µg/kg). Revisamos los principales trabajos que demuestran su eficacia, superioridad y seguridad. Finalmente, hacemos una revisión del tratamiento de las leishmaniasis. El antimonio pentavalente continúa siendo el fármaco de elección. Otros productos empleados son: pentamidina, sulfato de paramomicina, alopurinol, ketoconazol e itraconazol y más recientemente anfotericina liposomal (AU)