[Evolution in muscle strength in critical patients with invasive mechanical ventilation]. / Evolución de la fuerza muscular en paciente críticos con ventilación mecánica invasiva.

OBJECTIVE: To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. MATERIAL AND METHOD: A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. INCLUSION CRITERIA: Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC< 48, MRC ≥ 48) after the first measurement. RESULTS: Thirty-four patients were assessed. Independent outcomes associated with muscle strength weakness were: days with cardiovascular SOFA >2 (P<.001) and days with costicosteroids (P<.001). Initial MRC in MRC<48 group was 38 (27-43), and 52 (50-54) in MRC ≥ 48. The largest muscle strength gain was obtained the first week (31% versus 52%). A MRC < 48 value was associated with more MV days (P<.007) and a longer ICU stay. (P<.003). CONCLUSION: The greatest muscle strength gain after withdrawing of the sedatives was achieved in the first week. Muscle strength loss was associated with a cardiovascular SOFA > 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay.

Analytical study proving alprazolam degradation to its main impurity triazolaminoquinoleine through Maillard reaction.

Triazolaminoquinoleine is rapidly formed in formulations of alprazolam tablets in presence of excipients, and its generation is speeded up with increasing temperature and humidity. The present paper deals with detailed quantitative and qualitative studies into the nonactive constituents of the formulation in order to determine the excipient (or the mixture) responsible for the degradation. Our studies have demonstrated that reducing carbohydrate excipients play a fundamental role in the generation of triazolaminoquinoleine, with lactose as the main one responsible, through a Maillard reaction. In order to demonstrate the validity of the proposed degradation mechanism, p-nitrobenzaldehyde has been employed as a model of reaction of the nucleophylic attack of amino-opened structure of alprazolam to an aldehyde to generate the first intermediate involved in Maillard reaction, a Schiff base. This model enables the identification of all the intermediates by mass spectrometry and/or nuclear magnetic resonance techniques, with the outcome of this experiment leading to a full understanding of the generation pathway. Calcium carbonate has been proposed as a possible tablet diluent replacing lactose in the pharmaceutical formulation.

Ultra rapid liquid chromatography as second dimension in a comprehensive two-dimensional method for the screening of pharmaceutical samples in stability and stress studies.

Separation orthogonality has been explored with respect to comprehensive two-dimensional liquid chromatography (2D-LC) for different reversed-phase stationary phases. The outcome of this study points out an SB-CN x BEH-C18 combination, used in the first and the second dimension, respectively, as the most orthogonal chromatographic system for the samples assayed. The present investigation reports the employment of an ultra high pressure liquid chromatography system (UPLC) as the second chromatographic dimension, increasing the sensitivity and the speed, completing the whole chromatographic separation in a reasonable time frame. Finally, an off-line 2D-LC method with diode array detection based on the UPLC has been optimized, allowing the separation and minimizing the run time. SB-CN and BEH-C18 were employed as first and second dimension, respectively, with gradient elution applied in each dimension. Alprazolam degraded tablets were studied as a proof of concept of the utility of this type of setups for impurity profiling of complex samples.

Isolation, identification and determination of the major degradation product in alprazolam tablets during their stability assay.

The presence of a degradation product of alprazolam tablets that emerged throughout a short-stability assay has been determined and properly characterized. For this purpose an efficient methodology has been successfully applied, including SPE and HPLC methods for isolation and purification, respectively. LC/MS, MS/MS, 1H NMR, 13C NMR, UV and IR have been employed for structural elucidation confirming the identity of this impurity as 7-chloro-1-methyl-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-4-amine or triazolaminoquinoleine. The impurity, previously described as a long-term photodegradation product of alprazolam active pharmaceutical ingredient, was rapidly formed in the absence of light, but required the presence of excipients and its rate of formation increased with heat and humidity. In addition, a LC method has been developed and validated including triazolaminoquinoleine for the adequate determination of alprazolam and its mayor degradation product in tablets as pharmaceutical forms.

Situación de las profesionales del fitness: Análisis de caso de la ciudad de Huesca / Female Fitness Professionals: A Case Study in the City of Huesca

La situación laboral de la mujer en España ha sufrido una gran evolución y a pesar de que hay estudios que indican las diferencias en las trayectorias laborares en función del género, apenas analizan el sector del Fitness. Nuestro objetivo es describir la situación laboral de la mujer en este ámbito y sus condiciones conociendo su percepción acerca de posibles desigualdades a raíz del género. Para ello se ha empleado una metodología cuantitativa de corte descriptivo, realizándose un estudio transversal basado en la aplicación de un cuestionario autoadministrado de diseño propio. Las 33 mujeres de Huesca (España) que participaron en el estudio muestran un sector joven y con formación universitaria, pero perciben mayores dificultades para ser contratadas, para promocionar, y para conciliar, que los hombres. (AU)

The situation of women in the labour market in Spain has undergone a great evolution, and although there are some studies on the differences in professional careers depending on gender, fitness has been scarcely analysed. Our objective is to describe the situation of women in the labour market in this field and their conditions by understanding their perception about possible gender inequality. To this end, a descriptive quantitative methodology has been used, carrying out a cross-sectional study based on the application of a self-administered questionnaire of own elaboration. The 33 women from Huesca (Spain) who participated in the study represent a young and university-educated sector, but nevertheless, they seem to encounter greater difficulties to be hired, to get promoted, and to achieve work-life balance than men. (AU)

Tandem column for the simultaneous determination of arginine, ibuprofen and related impurities by liquid chromatography.

Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia than commercially available forms of ibuprofen. Ibuprofen and arginine have very different polarities and this becomes in a chromatographic problem, further complicated with the determination of related compounds, which is necessary in stability assays of the pharmaceutical forms. The common solution is the employment of two separate methods, but this is time consuming. A LC method has been developed to determinate both compounds and related impurities in one run. Ibuprofen, arginine and three ibuprofen related impurities (B, E and J) have been baseline separated with isocratic conditions at pH 3.0 and run time under 20 min by employing a tandem combination of two different stationary phases: first a ZORBAX SB-C18 column from Agilent (250 mm x 4.6 mm and 5 microm) and downstream a SUPELCOSIL LC-NH2 column from Supelco (150 mm x 4.6 mm and 3 microm). The octadecyldiisobutylsilane column provides the separation of ibuprofen and its impurities by a hydrophobic mechanism, whereas aminopropyl column offers selective retention of arginine by dipolar interaction mechanism. Method has been successfully validated following ICH guidelines and it has been demonstrated to be reliable for arginine, ibuprofen and related impurities determination in sachets of two different dosages as pharmaceutical forms. Moreover, stress test has proved the selectivity of the method for degradation products, such as those that can emerge throughout long-term stability assays.

LC methods for acyclovir and related impurities determination.

Acyclovir, guanine, and impurity A have been baseline separated with isocratic conditions at pH=3.0 and run time under 15 min by employing a SB-CN column from Agilent (150 mm x 4.6mm and 3.5 microm). Moreover, when run time was increased to 40 min six impurities (guanine, impurities A, F, G, Vir 3/4 and N(7)) plus acyclovir were separated in the same conditions. The mobile phase consisted of buffer A/acetonitrile 96:4 (v/v), being buffer A:25 mM H(3)PO(4) (Milli-Q H(2)O) brought to pH 3.0 with KOH. The same column provided separation for all the seven impurities described in pharmacopoeia, including impurity C, which coeluted with acyclovir in the previous conditions with a mobile phase prepared with 25 mM phosphoric acid (pH=1.8)/acetonitrile 96:4 (v/v). The method has been validated following ICH guidelines and it has demonstrated to be reliable for acyclovir and its impurities determination.

Age-related changes in calcium homeostatic mechanisms in synaptosomes in relation with working memory deficiency.

Aging is associated with alterations in different systems that govern neuronal calcium homeostasis. This study was designed to determine whether any of these alterations may contribute to the decline in spatial working memory that is observed in old rats. Several parameters [initial (5 s) and steady state (15 min) 45Ca2+ uptake, FCCP-releaseable 45Ca2+, [Ca2+]i levels, depolarization-induced phosphoprotein (P97, PP65, P42) dephosphorylation and acetylcholine levels and release) involved in calcium homeostasis/signaling were determined in whole brain synaptosomes derived from adult (9-month-old) and old (24-month-old) rats that were evaluated for spatial memory performance in the eight-arm radial maze. The neurochemical analysis indicated that both the 9- and 24-month-old rats were impaired with respect to 3-month-old animals. When learners (animals reaching criterion; RC) were compared to memory impaired rats (MI), it was found that the FCCP-releaseable 45Ca2+ of synaptosomes, that reflects mitochondrial calcium, was lower in the MI than the RC rats and was correlated with the behavioral performance of the rats in their first testing sessions. The results suggest that the loss of calcium uptake capacity in synaptic mitochondria during aging may be associated with impaired working memory in old animals.

The activity of synaptosomal calcium channels is inversely correlated with working memory performance in memory impaired, aged rats.

Aged, memory-impaired rats do not learn an 8-arm radial maze task but differ in their performance along testing. The aim of this study was to determine whether any of the systems that govern calcium homeostasis in synaptosomes may be related to that difference in performance. A negative correlation between initial (5 s) K(+)-stimulated 45Ca2+ uptake and the behavioral scores from the last testing sessions was obtained K(+)-stimulated 45Ca2+ uptake showed also a negative correlation with an improvement score that evaluates the progress made by the rat along testing. The results support the notion that calcium inflow through synaptosomal voltage gated calcium channels in old rats is inversely correlated with their behavior. This may explain the beneficial effects of organic calcium channel blockers on behavioral performance in aged animals.

Rapid analytical procedure for neomycin determination in ointments by CE with direct UV detection.

The purpose of this study was the development of an analytical methodology for the determination of neomycin in a complex pharmaceutical preparation. The simplified methodology consisted of a primary liquid-liquid extraction, employing a mixture of chloroform and water (1.25:1, v/v) and subsequent analysis by CE applying a capillary zone electrophoresis method with a 30 cm (effective length), 50 microm (internal diameter) polyacrylamide-coated silica capillary. The background electrolyte consisted of 35 mM phosphate and 15 mM acetate buffer set at pH 4.7, under normal polarity mode and direct UV detection at 200 nm. The separation of the target analyte from the complex matrix was accomplished in less than 3 min. The analytical method was successfully validated in order to verify its proper selectivity, linearity, accuracy and precision for the goal intended and its further implementation for the quantification of the active compound in the pharmaceutical speciality for quality control.

Infertilidad masculina / Male infertility

Se estima que aproximadamente un 15 por ciento de las parejas son incapaces de concebir luego de un año de relaciones sexuales no protegidas; 30 por ciento son debidas a factor femenino y 30 por ciento a factor masculino. El 40 por ciento restante es de causa mixta. La evaluación inicial de rutina en el varón (que incluye una detallada historia clínica, examen físico y test básicos como perfil hormonal y análisis seminal) es por lo tanto esencial para la mejoría de su fertilidad. El varicocele, criptorquidia no tratada y las infecciones del tracto urogenital son las causas identificables más frecuentes de infertilidad masculina. Causas menos frecuentes son las disfunciones sexuales, trastornos endocrinos y efectos adversos de medicamentos. Los tratamientos para estas patologías han sido efectivos en la mayoría de los casos, permitiendo a un importante número de parejas concebir en forma espontánea. Si esto no es posible, las parejas pueden recurrir a técnicas de reproducción asistida de baja complejidad, tales como la Inseminación Intrauterina. Y sólo en aquellos casos con problemas más severos recurriremos a técnicas de reproducción de alta complejidad como por ejemplo el ICSI (Inyección Intracitoplasmática de Espermatozoides). Importantes progresos en el área de la Microcirugía permiten no sólo reparar la vía seminal en muchos casos, sino también recuperar espermatozoides de pacientes con atrofia testicular. En los últimos años, junto con el ICSI, han sido una importante contribución.

It is estimated that approximately 15 percent of couples are unable to conceive after one year of contraceptive-free intercourse; 30 percent of which are due to female factors and 30 percent to malefactors. The remaining 40 percent are due to both partners. A routine initial evaluation of the male partner (including detailed medical history, physical exam and basic tests such as hormonal profile and semen analysis) is therefore essential, for improvement of their fertility. Varicocele, untreated Cryptorquidism, infections (eg. epididymitis, orquitis, prostatitis and vesiculitis, most of which are related with sexually transmitted diseases) are the most frequent causes of male infertility. Other minor causes include sexual dysfunctions, drug adverse effects, exposure to radiationor contaminants, endocrine and genetic factors. Treatment for this condition has been effective in most cases, allowing a significant proportion of couples to conceive spontaneously. Whenever this is not possible, patients may resort to low complexity techniques such as artificial insemination, and only in more severe cases, to advanced assisted reproduction techniques such as In Vitro Fertilization (IVF) and in particular Intracytoplasmic Sperm injection (ICSI).Microsurgery has also progressed. Not only used to repair the seminal path when obstructed, but also to recover sperm from patients with testicular atrophy. In recent years, these techniques, together with ICSI, have made an important therapeutic contribution.

Alteration of the electrophoretic pattern of myofibrillar proteins in fish mince during frozen storage.

A study was made of the variations in the electrophoretic profile of myofibrillar proteins in the muscles of blue whiting (Micromesistius poutassou R.), horse mackerel (Trachurus trachurus L.) and mackerel (Scomber scombrus L.). It was shown that all species presented different deterioration patterns during frozen storage. The fish were caught at two separate times of the year (winter and summer) and were stored frozen at -18 degrees C for 1 year. The results indicate that during frozen storage, electrophoretic patterns varied according to species. Comparison of myosin heavy chain/actin (MHC/A) ratios indicates that blue whiting is the species that undergoes most alteration, and that this is more intense in fish caught in the summer than in the winter. Alteration of the MHC/A ratio was similar in horse mackerel and mackerel caught in the winter, whereas in the summer horse mackerel proved to be the most stable species. In all cases, the reduction of the MHC/A ratio was due essentially to alteration of the MHC, an effect which was particularly marked in blue whiting. Tropomyosin remained stable throughout the storage period in all three species.

[Prevalence of calorie protein malnutrition among patients in chronic hemodialysis]. / Prevalencia de desnutrición calórico proteica en pacientes hemodializados crónicos.

BACKGROUND: Malnutrition has been strongly associated with morbidity and mortality in hemodialysis patients. In the other hand, dialysis allows a nutritional improvement in patients with more than 12 months in dialysis. AIM: To study the prevalence of malnutrition among patients in hemodialysis. PATIENTS AND METHODS: We measured clinical, anthropometric and biochemical parameters of nutritional status in chronic hemodialysed patients. Results were related to individual time in dialysis. Patients with more and less than 12 months in dialysis were compared. RESULTS: Twenty nine patients (18 male) aged 14 to 65 years old, were studied. Mean caloric intake was 23.8 Cal/Kg and protein intake was 0.7 g/Kg. Mean body mass index was 21.7 +/- 3.7 kg/m2 Thirty eight percent of patients had a body mass index of less than 20 kg/m2. Mean serum albumin was 4.1 +/- 0.7 g/L; mean prealbumin was 33.5 +/- 7.9 mg% and creatinine was 9.6 +/- 2.8 mg%. Serum cholesterol was 182 mg% and triacylglycerol 129 mg%. PCR was 42.2 +/- 18.8 and Kt/V was 1.45 +/- 0.3. We did not find a correlation between nutritional markers and time in dialysis or a difference in nutritional parameters between patients with less or more than 12 months in dialysis. CONCLUSIONS: These patients in chronic dialysis have a high prevalence of caloric malnutrition, which may be due to a poor caloric intake. Protein malnutrition parameters were normal in most patients. The absence of abnormal lipid levels, common in chronic renal failure, is noticeable.

Frozen storage of dressed and pre-fried portions of minced sardine muscle.

The aim of this work was to study the modifications occurring during frozen storage (-18 degrees C) of dressed and pre-fried portions of minced muscle of the sardine (Sardina pilchardus). Various samples were prepared in order to discover the effect on the samples of different preparatory frying times, the influence of vacuum-packing and the possible alterations in the state of preservation of the portions due to the presence of anti-oxidant agents. The results indicate that the presence of tocopherols did not have the expected effect on rancidity; it reduced the degree of rancidity reached during storage only slightly, while texture with respect to the control sample remained the same. Although the washed-muscle sample presented minimum rancidity values, the tasting panel awarded it the lowest score for acceptability. In contrast, the vacuum-packed sample presented less toughness and rancidity and was considered more acceptable, in the light of which this latter procedure would appear to be the best suited for frozen storage for pre-fried battered sardine portions.

Restless legs syndrome and paroxetine.

Restless legs syndrome is a frequent dyssomnia with well-known clinical features but uncertain origin and treatment. This paper describes a case of restless legs syndrome worsened by paroxetine. A possible pathogenic hypothesis related to the attributed neurochemical properties of the drug is proposed.

[Child abuse in Tlaxcala: a case-control study]. / El niño maltratado en Tlaxcala: estudio de casos.

A longitudinal, retrospective and descriptive study about child abuse was carried out in the Hospitals of the Tlaxcala Secretariat of Health, Mexico. The information was obtained from hospitalized children's charts between January first and November 30, 1991. The charts included were those belonging to zero to 14 year old children with injuries, poisoning, and II-III degrees of malnutrition. Four child-abuse criteria were established: physical, sexual, non organic malnutrition and mixed (physical and non organic malnutrition). Two control groups were defined. Different patterns were observed between accidental and non accidental injuries, malnutrition and poisoning among the case and the control groups. The study provides useful information for the integral diagnosis of child abuse in hospitalized children.

Evolución de la fuerza muscular en paciente críticos con ventilación mecánica invasiva / Evolution in muscle strength in critical patients with invasive mechanical ventilation

OBJETIVO: Evaluar la evolución de la fuerza muscular en pacientes críticos con ventilación mecánica (VM) tras la retirada de la sedación y hasta el alta hospitalaria. MATERIAL Y MÉTODO: Estudio de cohortes desarrollado en 2 unidades de cuidados intensivos (UCI) del Hospital Universitari de Bellvitge, de noviembre del 2011 a marzo del 2012. Se incluyó a pacientes consecutivos con VM > 72h. Variable dependiente: fuerza muscular mediante la escala Medical Research Council (MRC), el primer día que el paciente fue capaz de responder a 3 de 5 órdenes (día 1), cada semana, al alta de la UCI y al alta hospitalaria o 60 días. Variables independientes: factores asociados a la pérdida de fuerza, días libres de VM, días de estancia en la UCI y estancia hospitalaria. Los pacientes se distribuyeron en 2 grupos (MRC < 48, MRC ≥ 48) tras la primera medición. RESULTADOS: Se evaluó a 34 pacientes. Variables independientes asociadas a pérdida de fuerza: días con SOFA cardiovascular > 2 (p < 0,001) y días con corticoides (p < 0,001). MRC inicial para el grupo MRC < 48: 38 (27-43) y 52 (50-54) para el grupo MRC ≥ 48. La mayor ganancia de fuerza se obtuvo la primera semana (31% versus 52%). Un MRC < 48 se asoció a más días de VM (p < 0,007) y mayor estancia en la UCI (p < 0,003). CONCLUSIONES: La mayor ganancia de fuerza tras retirar la sedación se consigue la primera semana. La pérdida de fuerza se asocia a un valor de SOFA cardiovascular > 2 y al uso de corticoides. Los pacientes con MRC < 48 presentan mayor duración de la VM y mayor estancia en UCI

OBJECTIVE: To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. MATERIAL AND METHOD: A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. Inclusion criteria: Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC< 48, MRC ≥ 48) after the first measurement. RESULTS: Thirty-four patients were assessed. Independent outcomes associated with muscle strength weakness were: days with cardiovascular SOFA >2 (P<.001) and days with costicosteroids (P<.001). Initial MRC in MRC < 48 group was 38 (27-43), and 52 (50-54) in MRC ≥ 48. The largest muscle strength gain was obtained the first week (31% versus 52%). A MRC < 48 value was associated with more MV days (P < .007) and a longer ICU stay. (P < .003). CONCLUSION: The greatest muscle strength gain after withdrawing of the sedatives was achieved in the first week. Muscle strength loss was associated with a cardiovascular SOFA > 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay

Expresión y actividad de proteínas de multirresistencia a drogas (MDR) en líneas celulares de cáncer de próstata / Expression and activity of multidrug resistance proteins in prostate cancer cell lines

Introducción: Nuestro grupo ha reportado previamente una asociación entre sensibilidad a quimioterapia y la expresión de proteínas MDR (P-Gp y MRP1) en líneas celulares y cultivos primarios de cáncer de próstata, quedando por estudiar la actividad de las mismas. Material y métodos: Se utilizó líneas celulares de cáncer de próstata PC3 y DU145. Se evaluaron los niveles de mARN de P-Gp y MRP1 mediante RT-PCR. La expresión de ambas proteínas se determinó mediante inmunofluorescencia. Se estableció un ensayo funcional en base a la acumulación de sustratos fluorescentes (DiOC2(3) para P-gp y CFDA para MRP1) y al uso de inhibidores específicos para cada proteína (Ciclosporina A para P-Gp y MK571 para MRP1). Las células se incubaron durante 60 minutos a 37ºC con o sin el inhibidor específico, seguido de otra incubación por 60 minutos agregando el sustrato fluorescente. La acumulación del sustrato fluorescente se determinó por citometría de flujo. Resultados: Las líneas celulares utilizadas sólo expresaron MRP1, mientras no se detectó P-Gp (mARN ni proteína). Mediante el ensayo funcional se observó que las células acumulaban más CFDA cuando eran tratadas con MK571. No se observó diferencias en la acumulación de DiOC(2)3 frente al tratamiento con Ciclosporina A. Conclusión: La mayor acumulación intracelular de CFDA frente al tratamiento con MK571 indica que la proteína MRP1 expresada en las líneas celulares utilizadas es funcional. P-Gp no se expresa en las líneas evaluadas. En estudios en curso nos encontramos evaluando la expresión y función de ambas proteínas en cultivos primarios.

Introduction: We have previously reported an association between sensitivity to chemotherapy and the expression of multidrug resistance proteins (MDR) (P-Gp and MRP1) in cell lines and primary cultures of prostate cancer. Activity remains to be studied. Material and methods: Prostate cancer cell lines PC3 and DU145 were used. Levels of mRNA of P-Gpand MRP1 using RT-PCR, were evaluated. The expression of both proteins was determined using immunofluorescence. A functional assay based on the accumulation of fluorescence substrates (DiOC2(3) for P-Gp and CFDA for MRP1) was established. Cells were incubated for 60 minutes at 37C with/without the specific inhibitor, followed by another 60 minutes incubation adding the fluorescence substrate. Accumulation of fluorescence substrate was determined by flow citometry. Results: Cell lines expressed only MRP1, whereas P-Gp (mRNA/protein) was not detected. Using the functional assay, we found that cells accumulated more CFDA when treated with MK571. No differences were seen in the accumulation of DiOC2(3) after treatment with ciclosporin A. Conclusion: The higher intracellular accumulation of CFDA after treatment with MK571 indicates that the MRP1 protein expressed in these cell lines is functional. P-Gp was not expressed in these cell lines. We are currently evaluating the expression and function of both proteins in primary cultures.