Manganese Defective Clustering: Influence on the Spectroscopic Features of Ceria-Based Nanomaterials.

The influence of manganese modification on the spectroscopic features of manganese-doped CeO2 systems synthesized by the microwave-assisted hydrothermal route and their correlation with the presence of O defective structures were verified, focusing on their interaction with poisonous atmospheres. Raman and electron paramagnetic resonance studies confirmed the presence of defective clusters formed by dipoles and/or quadrupoles. The number of paramagnetic species was found to be inversely proportional to the doping concentration, resulting in an increase in the Mn2+ signal, likely due to the reduction of Mn3+ species after the interaction with CO. X-ray photoelectron spectroscopy data showed the pure system with 33% of its cerium species in the Ce3+ configuration, with an abrupt decrease to 19%, after the first modification with Mn, suggesting that 14% of the Ce3+ species are donating one electron to the Mn2+ ions, thus becoming nonparamagnetic Ce4+ species. On the contrary, 58% of the manganese species remain in the Mn2+ configuration with five unpaired electrons, corroborating the paramagnetic feature of the samples seen in the electron paramagnetic resonance study.

White fish reduces cardiovascular risk factors in patients with metabolic syndrome: the WISH-CARE study, a multicenter randomized clinical trial.

BACKGROUND AND AIMS: Reduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate, and concerns about heavy metal contamination have limited consumption of oily fish. We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome. METHODS AND RESULTS: Multicenter randomized crossover clinical trial including 273 individuals with metabolic syndrome. An 8-week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with advice on a healthy diet, compared with no fish or seafood with advice on a healthy diet. Outcomes were lipid profile, individual components of the metabolic syndrome, serum insulin concentrations, homeostasis model of insulin resistance, serum C-reactive protein and serum fatty acid levels. We found a significant lowering effect of the intervention with white fish on waist circumference (P < 0.001) and diastolic blood pressure (P = 0.014). A significant lowering effect was also shown after the dietary intervention with fish on serum LDL concentrations (P = 0.048), whereas no significant effects were found on serum HDL or triglyceride concentrations. A significant rise (P < 0.001) in serum EPA and DHA fatty acids was observed following white fish consumption. Overall adherence to the intervention was good and no adverse events were found. CONCLUSION: In individuals with metabolic syndrome, regular consumption of hake reduces LDL cholesterol concentrations, waist circumference and blood pressure components of the metabolic syndrome. CLINICAL TRIAL REGISTRY: White Fish for Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study, Registered under ClinicalTrials.gov Identifier: NCT01758601.

GC-MS determination of malondialdehyde, acrolein, and 4-hydroxy-2-nonenal by ultrasound-assisted dispersive liquid-liquid microextraction in beverages.

A new, fast, simple, and effective ultrasound-assisted dispersive liquid-liquid microextraction procedure (UA-DLLME) for the gas chromatography-mass spectrometry (GC-MS) determination of malondialdehyde, acrolein, and 4-hydroxy-2-nonenal in beverages was successfully developed. 2,4-Dinitrophenylhydrazine derivatization was performed during extraction. An asymmetrical 3541//18 screening design and a central composite surface response design were used to investigate the influence of the most critical factors during the extraction process (ultrasound time and temperature, extraction and disperser solvents volumes, salt addition, and derivatization reagent concentration). According to FDA guidelines, the method was validated, achieving good linearities with r2 ≥ 0.9982, recoveries between 94.0 and 102.4%, and reproducibility with RSD lower than 4.5%. The method was applied to simultaneously determine the compounds in 60 different beverage samples, including beer, coffee, black tea, and fruit juices. The presence of secondary lipid oxidation products is demonstrated in beverages with a strong roasting process or oxidation.

In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells.

Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.

[Bronchospasm and flushing after vaccination with 23 serotype pneumococcal polysaccharide in chronic patients]. / Broncoespasmo y flushing tras la vacunación con neumococo polisacárida de 23 serotipos en pacientes crónicos.

OBJECTIVE: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23®). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance. METHODS: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted. RESULTS: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found. CONCLUSIONS: The reactions described do not appear in the PNEUMOVAX23® data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet.

Development of a partitioned liquid-liquid extraction- dispersive solid phase extraction procedure followed by liquid chromatography-tandem mass spectrometry for analysis of 3-monochloropropane-1,2-diol diesters in edible oils.

A fast and effective method using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach which includes partitioned liquid-liquid extraction (PLLE) and dispersive solid phase extraction (dSPE) clean-up step for the determination of seven 3-monochloropropane-1,2-diol (3-MCPD) fatty acid diesters in vegetable oils is developed and validated according to the Food and Drug Administration (FDA) guidelines. Due to the complexity of the matrices, combination of silica based sorbents (Silica Strong Anion Exchange (Si-SAX), Supel™ QuE Z-Sep+ (Z-Sep+) and Primary Secondary Amine (PSA) were tested for lipid removal. The effect of several experimental factors on the efficiency of the extraction procedure was studied by a screening design 3422//16 and a response surface Doehlert design. The separation and determination was carried out by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The method provided suitable linearity (r2 > 0.9960), precision (relative standard deviation (RSD) lower than 10%) and accuracy, in terms of recovery. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 10 to 20 µg kg -1 and from 25 to 50 µg kg-1, respectively. The recoveries at three spiking levels of 100, 250, and 500 µg kg-1 were over the range of 71.4-122.9% with RSD lower than 13%. The method was successfully applied in edible oils and fatty food samples. The results provide valuable information to assess the risk of exposure to these foodborne contaminants.

Linfoma no Hodgkin difuso de células B grande como linfoma primario de ovario. Presentación decaso / Diffuse large B-cell non-Hodgkin's lymphoma as primary ovarian lymphoma. Case presentation

Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1porciento de estos se presenta en ovario y el 1.5 porciento de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuenteses el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia.Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario.Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario. [AU]

A single growth hormone determination 30 minutes after the administration of the GHRH plus GHRP-6 test is sufficient for the diagnosis of somatotrope dysfunction in patients who have suffered traumatic brain injury.

UNLABELLED: As hypopituitarism is frequent in patients who have suffered a traumatic brain injury (TBI) a hormonal check-up is necessary. However, the prevalence of TBI is so large that the number of potential candidates to be tested is difficult to manage, in particular for GH deficiency diagnosis that requires cumbersome and expensive dynamic tests. GHRH plus GH-releasing hexapeptide (GHRP-6) is a safe and effective test capable of segregating normal subjects from GH deficient patients. As the GHRH+GHRP-6 test induces GH peaks consistently in the first 30 min, the working hypothesis assessed in this study was whether a single determination of GH 30 min after stimulus could provide the same biochemical classification as the whole secretory curve. A total of 83 subjects who suffered TBI at least one year before the study were administered GHRH 1 mug/kg iv plus GHRP-6 1 mug/kg iv at 0 min, and blood samples were obtained at regular intervals. GH was determined in all samples. An excellent correlation was observed between GH values at 30 min and GH peaks (r=0.972, p<0.0001). When comparing the 30-min GH values against the peaks, the biochemical classification changed only in 5 out of 83 subjects from normal GH secretion to uncertain. CONCLUSIONS: The GHRH+GHRP-6 test is convenient, safe and in patients with TBI can be reduced to a single fixed GH determination 30 min after stimulus without losing diagnostic power.

Campaña Reactívate: un plan de acción saludable sobre actividad física, nutrición y salud mental en tiempos de pandemia / Reactívate campaign: a healthy action plan on physical activity, nutrition and mental health in a time of pandemic

JUSTIFICACIÓN: la pandemia ha cambiado los hábitos de la población influenciados, principalmente, por las restricciones establecidas. La farmacia comunitaria ha sido clave proporcionando información sobre la COVID-19 y aconsejando hábitos de vida saludables adaptados a la nueva situación. En este marco, surgió la campaña REACTÍVATE como plan de acción basado en utilización de redes sociales como instrumento para proporcionar consejo farmacéutico.OBJETIVO: elaborar material formativo destinado a concienciar a la población general de la importancia de mantener o adquirir hábitos de vida saludables adaptados a la situación de pandemia. Objetivos específicos: educar a la población sobre conceptos básicos de actividad y ejercicio físico, así como divulgar conceptos de higiene postural para prevenir lesiones. Resaltar las propiedades funcionales de determinados alimentos que sirven para mejorar la salud de la población. Concienciar a la población sobre la importancia de la salud mental y el control del estrés sin descuidar patologías como Alzheimer.METODOLOGÍA Y MATERIAL: 1.Selección de expertos en distintas áreas: bloque actividad física e higiene postural, bloque nutrición y bloque salud mental. 2. Elaboración de cronograma de difusión: Reactívate y Reactívate verano.3.Desarrollo material para difusión : cartelería promocional para la farmacia comunitaria, newsletter, infografías descargables, vídeos (1-2 min) y retos en redes sociales (Página Web, Facebook, Twitter e Instagram).RESULTADO Y DISCUSIÓN: se han elaborado y difundido 1 cartel, 2 vídeos presentación, 1 vídeo resumen, 10 infografías, 7 vídeos de información y consejos y 4 vídeos de retos distribuidos con una media de 8 días entre entregas del 18 de febrero al 20 de octubre de 2021. (AU)

Impacto de la Campaña Reactívate: un éxito en tiempos de pandemia / Impact of the Reactivate Campaign: a success in times of pandemic

JUSTIFICACIÓN: la campaña REACTÍVATE, creada y promovida por la Sociedad Española de Farmacia Clínica, Familiar y Comunitaria (SEFAC), ha pretendido inculcar a la población cómo adquirir y mantener hábitos de vida saludable en tiempos de pandemia donde nuestro estilo de vida ha sufrido cambios importantes. Las redes sociales han sido nuestro gran aliado en su difusión. Es necesario estimar el alcance en la población y en diferentes redes sociales para la implementación de futuras campañas.OBJETIVOS: analizar y valorar el alcance y participación ciudadana en las dos ediciones de la campaña REACTÍVATE.MATERIAL Y MÉTODOS: se ha realizado una valoración sobre los datos de participación generados en redes sociales y webs gestionadas por SEFAC, en las dos ediciones de la campaña, REACTÍVATE y REACTÍVATE VERANO, entre febrero y octubre de 2021.Las variables analizadas para valorar el impacto de la campaña fueron el número de descargas del material de la campaña, las impresiones existentes en redes sociales y la participación de particulares y personas famosas mediante videos, fotografías y retos.RESULTADOS Y DISCUSIÓN: en la primera edición, ya concluida, se registraron 2,4 millones de impresiones en redes sociales, más de 12000 visualizaciones de vídeos, más de 120 aportaciones de particulares con videos, fotos y retos, y la participación en la campaña de 5 personas conocidas del mundo del deporte. De la segunda edición, aunque todavía no ha concluido, se suman 500.000 impresiones en redes sociales, cerca de 5000 visualizaciones de vídeo y alguna aportación particular con vídeos. El tiempo medio entre publicaciones fue de 8 días en Reactívate (mínimo 0, máximo 32) y de 9 días en Reactívate Verano (mínimo 0, máximo 77) lo que demuestra mayor discontinuidad en la segunda parte del proyecto. (AU)

Evaluación de la mejora de conocimientos de los participantes del taller de tapón de oído, durante las jornadas SEFAC 2021 / Evaluation of the improvement of the knowledge of the participants of the earplug workshop during the SEFAC 2021 conference

JUSTIFICACIÓN: SEFAC ha retomado la celebración de las jornadas SEFAC 21, en las 15 delegaciones, de manera presencial, en sesiones de mañana y de tarde para facilitar la asistencia. Uno de los talleres del programa ha sido: “Indicación farmacéutica en tapón de oído: prevención, tratamiento y disolución”.OBJETIVO: el objetivo principal del trabajo es evaluar la mejora de conocimiento de los farmacéuticos tras la asistencia al taller. Como objetivo general, queremos conocer la utilidad y eficacia del taller en las jornadas de SEFAC tras la asistencia al mismo.MÉTODO: para conseguir los objetivos propuestos, el grupo que elaboró el taller preparó un cuestionario tipo test, que posteriormente aprobó el comité científico, con cinco preguntas y cuatro respuestas posibles en cada una de ellas. A través de la descarga de una APP, los participantes debían contestar el cuestionario antes del inicio del taller e inmediatamente después de finalizarlo, teniendo el cuestionario las mismas preguntas en ambos casos.RESULTADOS: participantes que cubrieron el cuestionario: 278, en la mañana 175 y en la tarde 103.La primera pregunta no presenta cambios porcentuales grandes, ya que los aciertos eran muy elevados inicialmente. La segunda muestra una mejora significativa en todas las ciudades. En la tercera pregunta, el porcentaje de aciertos es similar al de la pregunta dos. La cuarta presenta una diferencia amplia entre antes y después. En la quinta pregunta se obtienen resultados de mejora próximos al 25 %.Los talleres con mejoras significativas en la formación tras la realización del cuestionario son: Barcelona, Badajoz, Alicante, Madrid y Santander. (AU)

Tratamiento farmacológico y no farmacológico. Adherencia e inercia terapéutica / Pharmacological and non-pharmacological treatment. Adherence and therapeutic inertia

La hipertensión arterial (HTA) continúa siendo el principal factor evitable de enfermedad cardiovascular (ECV) y de mortalidad por cualquier causa tanto en Europa como en el mundo y existe una gran cantidad de evidencias que demuestran que la reducción de la presión arterial (PA) reduce sustancialmente la morbimortalidad prematura1.El objetivo de reducir la presión arterial de nuestros pacientes radica fundamentalmente en frenar la evolución de la enfermedad arteriosclerótica y sus complicaciones cardiovasculares y renales, entre otras.En estos momentos contamos con dos estrategias terapéuticas que han demostrado un beneficio claro sobre la ECV: las intervenciones en el estilo de vida y el tratamiento farmacológico. No hay duda de que las intervenciones en el estilo de vida pueden reducir la PA y deben indicarse en todos los casos, aunque su impacto no sea tan potente como el tratamiento farmacológico1.Dado que los tratamientos de los factores de riesgo cardiovascular (FRCV) se prolongarán durante décadas, es importante que sean bien tolerados además de efectivos e impacten de forma positiva en la calidad de vida de los pacientes. (AU)

Programa formativo CRÓNICA. Continuidad asistencial en hipertensión arterial / CRONICA training programme. Continuity of care in arterial hypertension

INTRODUCCIÓN: el Programa formativo Crónica, Continuidad Asistencial surge como una necesidad de abordaje conjunto entre médicos de familia y farmacéuticos comunitarios, de diferentes patologías crónicas con alta prevalencia en nuestra sociedad. Recientemente se ha puesto en marcha el primero de ellos: Crónica: Continuidad asistencial en hipertensión arterial, próximamente se lanzará el segundo, referido a la Salud Mental: Ansiedad y Depresión. La prevalencia mundial de la hipertensión en adultos es de 1280 millones en 2019 . La guía europea de HTA habla de un 30-45 % en adultos. En España el estudio di@betes prevalencia por edad en torno al 42,6 %, con un tercio de la población sin diagnosticar. El estudio Iberican informa de un 48 %. Ambos estudios describen grado de control desde un 29,9 % hasta un 58,5 %, valores lejanos a lo deseable. La colaboración entre profesionales sanitarios es de vital importancia para el correcto diagnóstico, seguimiento y control de estos pacientes. Para ello necesitamos una formación conjunta.OBJETIVOS: fomentar el conocimiento y el trabajo coordinado de farmacéuticos comunitarios y médicos de familia, mediante el diseño y elaboración de un programa formativo común para: •Conocer cómo realizar la medida correcta de la presión arterial, así como el cribado, diagnóstico, seguimiento y control de la misma.• Conocer las recomendaciones actuales de las guías en cuanto a factores de riesgo, cálculo de riesgo cardiovascular, clasificación, fenotipos, objetivos de control, tratamiento farmacológico y no farmacológico y adherencia.• Evaluación y correcta derivación a urgencias y emergencias hipertensivas de forma coordinada desde la farmacia comunitaria y el centro de salud. (AU)

Comorbid conditions in men with ED before and after ED diagnosis: a retrospective database study.

Although erectile dysfunction (ED) has been considered a complication of other medical conditions, clinicians and researchers suggest that ED may serve as a clinical marker of vascular health. This retrospective claims study examined the prevalence of predefined comorbid conditions in men with ED (N=301 994) in the 12 months before and the 6 months following ED diagnosis. Consistent with previous research, comorbid conditions were prevalent among men with ED. Comorbid conditions were most often diagnosed before an ED diagnosis, although new diagnoses in the 6 months following an ED diagnosis were common and occured more frequently than new diagnoses in a matched sample of men without ED during the same period. Differences by age, region and insurance coverage for ED medications were also examined. Findings support previous research that suggests ED may serve as a marker for previously undetected comorbid conditions.

Effect of immunomodulatory therapy and other factors on employment loss time in multiple sclerosis.

The factors that influence time missed from work among individuals diagnosed with multiple sclerosis were the focus of this study. Records of individuals who were employed and diagnosed with multiple sclerosis between the years 1999 and 2002 (N=284) were examined for details pertaining to their medical claims. Multivariate regressions, controlling for demographic characteristics, type of immunomodulatory medication, and overall severity of illness, were used in the examination of the total number of days missed from work for any reason and those missed due to absenteeism, short-term disability, or worker's compensation. Results indicate that lost work time is affected by severity of illness, and type of immunomodulatory therapy. Comparing individuals treated with the specific immunomodulator glatiramer acetate, interferon beta-1a (intramuscular), or interferon beta-1b, to those who did not receive multiple sclerosis medications of this type; only glatiramer acetate was associated with significantly fewer days missed from work for short term disability (18.24 fewer days, P<0.03), worker's compensation (29.50 fewer days, P<0.04) or any reason (53.70 fewer days, P< 0.003).

Obesity and glycemic control in patients with diabetes mellitus: Analysis of physician electronic health records in the US from 2009-2011.

AIMS: Examine the association between obesity and glycemic control among patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). METHODS: Data from US physician electronic health records (Humedica®) from 2009-2011 were utilized. Patients were defined as having above-target glycemic control if they had an HbA1c ≥7% at any time during the study period. Multinomial logistic regressions were conducted separately for T1DM and T2DM patients, and examined associations between BMI categories and probability of having above-target glycemic control (≥7% and <8%, ≥8% and <9%, or ≥9%) while controlling for patient demographics, general health, comorbid conditions, and antihyperglycemic medication use. RESULTS: There were 14,028 T1DM and 248,567 T2DM patients; 47.8% of T1DM and 63.4% of T2DM were obese (BMI ≥30kg/m(2)). For T1DM, being overweight (BMI 25-<30), obese class I (30-<35), II (35-<40), or III (≥40) was associated with a significantly higher probability of having HbA1c≥8% and <9% or ≥9%, while being overweight was associated with a significantly higher probability of having HbA1c ≥7% and <8% compared to normal BMI (BMI≥18.5 and<25). For T2DM patients, being overweight, obese class I, II, or III was associated with a significantly higher probability of having HbA1c ≥7% and <8%, ≥8% and <9%, or ≥9%. CONCLUSIONS: For both T1DM and T2DM patients, there were positive and statistically significant associations between being overweight or obese and having suboptimal glycemic control. These findings quantify the associations between obesity and glycemic control, and highlight the potential importance of individual characteristics on glycemic control.

Differentiating Tumor Progression from Pseudoprogression in Patients with Glioblastomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI.

BACKGROUND AND PURPOSE: Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. MATERIALS AND METHODS: Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%-75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. RESULTS: Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non-true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from nonpseudoprogression (true progression and mixed) with an area under the curve of 0.807. CONCLUSIONS: DTI and DSC perfusion imaging can improve accuracy in assessing treatment response and may aid in individualized treatment of patients with glioblastomas.

cis-FFA do not alter membrane depolarization but block Ca2+ influx and GH secretion in KCl-stimulated somatotroph cells. Suggestion for a direct cis-FFA perturbation of the Ca2+ channel opening.

It has been reported that cis-unsaturated free fatty acids (cis-FFA) block intracellular Ca2+ rise in EGFR T17 and GH3 cells by perturbing the generation of Ins(1,4,5)P3. In the present work, it was found that cis-FFA did not alter potassium-induced cell depolarization in GH3 cells, while blocking Ca2+ rise and GH secretion. Interestingly enough, saturated or trans-unsaturated FFA exert the opposite actions, i.e., they block cell depolarization without altering Ca2+ rise and hormone secretion. As depolarization activates GH3 cells via direct opening of Ca2+ channels with no generation of intracellular mediators, these results suggest that cis-FFA act by a direct perturbation of the Ca2+ channel opening.

Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage.

UNLABELLED: It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index. IN CONCLUSION: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.