Optimization of Free Phytoprostane and Phytofuran Production by Enzymatic Hydrolysis of Pea Extracts Using Esterases.

Given the growing interest in phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in the fields of plant physiology, biotechnology, and biological function, the present study aims to optimize a method of enzymatic hydrolysis that utilizes bacterial and yeast esterases that allow the appropriate quantification of PhytoPs and PhytoFs. To obtain the highest concentration of PhytoPs and PhytoFs, a response surface methodology/Box-Behnken design was used to optimize the hydrolysis conditions. Based on the information available in the literature on the most critical parameters that influence the activity of esterases, the three variables selected for the study were temperature (°C), time (min), and enzyme concentration (%). The optimal hydrolysis conditions retrieved differed between PhytoPs (21.5 °C, 5.7 min, and 0.61 µg of enzyme per reaction) and PhytoFs (20.0 °C, 5.0 min, and 2.17 µg of enzyme per reaction) and provided up to 25.1- and 1.7-fold higher contents relative to nonhydrolyzed extracts. The models were validated by comparing theoretical and experimental values for PhytoP and PhytoF yields (1.01 and 1.06 theoretical/experimental rates, respectively). The optimal conditions were evaluated for their relative influence on the yield of individual nonesterified PhytoPs and PhytoFs to define the limitations of the models for obtaining the highest concentration of most considered compounds. In conclusion, the models developed provided valuable alternatives to the currently applied methods using unspecific alkaline hydrolysis to obtain free nonesterified PhytoPs and PhytoFs, which give rise to more specific hydrolysis of PhytoP and PhytoF esters, reducing the degradation of free compounds by classical chemical procedures.

Establecimiento de un protocolo para el uso de la heparina en pacientes con características especiales / Set up of a protocol for heparin use in special patients

Las HBPMs (heparina de bajo peso molecular) tienen numerosas ventajas sobre la heparina no fraccionada (HNF) como seguridad, eficacia, biodisponibilidad, menor monitorización y una respuesta anticoagulante persistente. Pero, existe cierta preocupación en su manejo para determinados pacientes que requieren un control especial como en insuficiencia renal, mayores de 75 años, obesidad y embarazo. El objetivo de este estudio fue la realización de un protocolo consensuado entre los Servicios de Farmacia, Hematología y Medicina Interna, para el seguimiento y monitorización de HBPM en pacientes que requieren un especial control. Para ello, llevamos a cabo una revisión bibliográfica de las distintas heparinas en las situaciones comentadas. Basándonos en la evidencia disponible y en el consenso entre los miembros del grupo de trabajo, elaboramos el protocolo, recomendando unas dosis para profilaxis, tratamiento y monitorización, mediante la determinación del factoranti-Xa. Además, recogemos unas orientaciones sobre los valores terapéuticos del anti-Xa y unas pautas posológicas para la obtención de un anti-Xa en rango. La heparina seleccionada fue la enoxaparina, por su evidencia y disponibilidad en nuestro centro (AU)

Low-molecular weight (LMW) heparins bring a series of advantages as compared to non-fractionated heparin (NFH), such as safety, efficacy, bioavailability, fewer monitoring, and persistent anti-coagulant response. There exist, however, a concern about their use in particular patients that may require a special control, such as those with renal failure, age over 75 years, obesity, and pregnancy. The aim of this study was the set up between the department of Pharmacy, Hematology, and Internal Medicine of a consensus protocol for the follow-up ad monitoring of LMWH in patients requiring a special control. For this purpose, we carried out a bibliographical review of the different heparins used under de above mentioned conditions. Based on the evidence available and the consensus among the members of the working group, we established a protocol that contained recommendations on prophylaxis, management and monitoring by means of the determination of anti-Xa factor. Besides,we included some clues on the therapeutic figures of anti-Xa and administration schedules for obtaining anti-Xa values within the range. Enoxaparin was the selected heparin given the evidence and its availability at our center (AU)

[Set up of a protocol for heparin use in special patients]. / Establecimiento de un protocolo para el uso de la heparina en pacientes con características especiales.

Low-molecular weight (LMW) heparins bring a series of advantages as compared to non-fractionated heparin (NFH), such as safety, efficacy, bioavailability, fewer monitoring, and persistent anti-coagulant response. There exist, however, a concern about their use in particular patients that may require a special control, such as those with renal failure, age over 75 years, obesity, and pregnancy. The aim of this study was the set up between the department of Pharmacy, Hematology, and Internal Medicine of a consensus protocol for the follow-up ad monitoring of LMWH in patients requiring a special control. For this purpose, we carried out a bibliographical review of the different heparins used under de above mentioned conditions. Based on the evidence available and the consensus among the members of the working group, we established a protocol that contained recommendations on prophylaxis, management and monitoring by means of the determination of anti-Xa factor. Besides, we included some clues on the therapeutic figures of anti-Xa and administration schedules for obtaining anti-Xa values within the range. Enoxaparin was the selected heparin given the evidence and its availability at our center.

Las HBPMs (heparina de bajo peso molecular) tienen numerosas ventajas sobre la heparina no fraccionada (HNF) como seguridad, eficacia, biodisponibilidad, menor monitorización y una respuesta anticoagulante persistente. Pero, existe cierta preocupación en su manejo para determinados pacientes que requieren un control especial como en insuficiencia renal, mayores de 75 años, obesidad y embarazo. El objetivo de este estudio fue la realización de un protocolo consensuado entre los Servicios de Farmacia, Hematología y Medicina Interna, para el seguimiento y monitorización de HBPM en pacientes que requieren un especial control. Para ello, llevamos a cabo una revisión bibliográfica de las distintas heparinas en las situaciones comentadas. Basándonos en la evidencia disponible y en el consenso entre los miembros del grupo de trabajo, elaboramos el protocolo, recomendando unas dosis para profilaxis, tratamiento y monitorización, mediante la determinación del factor anti-Xa. Además, recogemos unas orientaciones sobre los valores terapéuticos del anti-Xa y unas pautas posológicas para la obtención de un anti-Xa en rango. La heparina seleccionada fue la enoxaparina, por su evidencia y disponibilidad en nuestro centro.

Mioclonias cervicales en paciente en tratamiento con etanercept / Myoclonus in patients treated with etanercept

No disponible

Análisis de la efectividad de un protocolo de antiemesis implantado en la Unidad de Oncología / Analysis of the effectiveness of an antiemetic protocol used in an oncology division

Objetivo Analizar la efectividad de un protocolo antiemético en pacientes que reciben quimioterapia. Método Estudio prospectivo en pacientes con tumores sólidos con quimioterapia en el hospital de día de Oncología entre enero 2006–2007.Se realizó una revisión bibliográfica analizando las recomendaciones de guías de práctica clínica. Se calculó el potencial emetógeno según nivel Hesketh (NH), estableciendo la premedicación antiemética de cada esquema. Se evaluó la efectividad de un protocolo antiemético mediante una encuesta como método de medida de episodios eméticos y náuseas en fase aguda y retardada. Resultados Ciento setenta y dos pacientes cumplimentaron la encuesta, 13,4% vomitaron en fase aguda y 16,9% en retardada, mediana número de veces 2 (1–8) y 1 (1–5) respectivamente. Con esquemas NH 4–5 18,5% experimentaron vómitos en fase aguda y 20,2% en retardada; náuseas en fase aguda 46% y 38,4% en retardada. El control de vómitos en pacientes con esquemas NH=1–3 fue del 100% en fase aguda y de 91,7% en retardada; notificaron náuseas un 27% en fase aguda y 31% en retardada. Los factores que más contribuyeron a la presencia de vómitos y náuseas fueron potencial emetógeno (p<0,05), vómitos en ciclo anterior (p<0,05) y edad<50 p lt 0 002DiscusiónLa pauta propuesta es eficaz en el control de vómitos para esquemas NH=–3. En esquemas altamente emetógenos, el protocolo antiemético es también eficaz aunque la protección no es completa. Este protocolo parece no ser tan efectivo en el control de náuseas, aunque este es un síntoma subjetivo de valoración compleja que no se mide de forma sistemática en ensayos clínicos (AU)

Objective To analyse the effectiveness of an antiemetic protocol in patients receiving chemotherapy treatment. Method Prospective study in patients with solid tumours receiving chemotherapy in an oncology day hospital between January 2006 and 2007. We conducted a literature review and an evaluation of the recommendations of different clinical practice guidelines. The emetogenic potential was calculated according to the Hesketh level (HL), and the antiemetic premedication was determined for each regimen. We evaluated the effectiveness of an antiemetic protocol by using a survey as a method for measuring emetic episodes and nausea in the acute and delayed phases.Results172 patients completed the survey. 13.4% vomited in the acute phase and 16.9% in the delayed phase; the median number of times was 2 (1–8) and 1 (1–5) for each respective phase. With treatment regimens classed as HL 4-5, 18.5% experienced vomiting in the acute phase and 20.2% in the delayed phase, with 46% experiencing nausea in the acute phase and 38.4% in the delayed phase. Control of vomiting in patients with treatment regimens classed as HL 1-3 was 100% in acute phase and 91.7% in the delayed phase; nausea was reported by 27% in the acute phase and 31% in the delayed phase. The factors that contributed the most to the presence of vomiting and nausea were the emetogenic potential of the treatment regimen (p<0.05), vomiting in the previous cycle (p<0.05) and age younger than 50 years (p<0.002).Discussion The proposed antiemetic protocol is effective for controlling vomiting in chemotherapy regimens with an HL of 1-3. For highly emetogenic regimens, the antiemetic protocol is also effective, but protection is not complete. This protocol seems less effective for controlling nausea, although this is a subjective symptom which is difficult to assess and not routinely measured in clinical trials (AU)

[Analysis of the effectiveness of an antiemetic protocol used in an oncology division]. / Análisis de la efectividad de un protocolo de antiemesis implantado en la Unidad de Oncología.

OBJECTIVE: To analyse the effectiveness of an antiemetic protocol in patients receiving chemotherapy treatment. METHOD: Prospective study in patients with solid tumours receiving chemotherapy in an oncology day hospital between January 2006 and 2007. We conducted a literature review and an evaluation of the recommendations of different clinical practice guidelines. The emetogenic potential was calculated according to the Hesketh level (HL), and the antiemetic premedication was determined for each regimen. We evaluated the effectiveness of an antiemetic protocol by using a survey as a method for measuring emetic episodes and nausea in the acute and delayed phases. RESULTS: 172 patients completed the survey. 13.4% vomited in the acute phase and 16.9% in the delayed phase; the median number of times was 2 (1-8) and 1 (1-5) for each respective phase. With treatment regimens classed as HL 4-5, 18.5% experienced vomiting in the acute phase and 20.2% in the delayed phase, with 46% experiencing nausea in the acute phase and 38.4% in the delayed phase. Control of vomiting in patients with treatment regimens classed as HL 1-3 was 100% in acute phase and 91.7% in the delayed phase; nausea was reported by 27% in the acute phase and 31% in the delayed phase. The factors that contributed the most to the presence of vomiting and nausea were the emetogenic potential of the treatment regimen (p<0.05), vomiting in the previous cycle (p<0.05) and age younger than 50 years (p<0.002). DISCUSSION: The proposed antiemetic protocol is effective for controlling vomiting in chemotherapy regimens with an HL of 1-3. For highly emetogenic regimens, the antiemetic protocol is also effective, but protection is not complete. This protocol seems less effective for controlling nausea, although this is a subjective symptom which is difficult to assess and not routinely measured in clinical trials.

[Treatment with cetuximab in metastatic colorectal cancer patients who do not express the epidermal growth factor receptor]. / Tratamiento con cetuximab en pacientes con cáncer colorrectal metastásico que no expresan el receptor del factor de crecimiento epidérmico.

OBJECTIVE: To evaluate the response to cetuximab, in terms of time passed until disease progression and overall survival, in patients with colorectal cancer (CRC) in which the epidermal growth factor receptor (EGFR) is undetectable. METHOD: Nine EGFR-negative patients (confirmed by an immunohistochemistry study), who were being treated with cetuximab, were selected. Variables collected: demographic data, diagnosis, previous treatments, time since first metastasis to start of treatment with cetuximab, adverse events and tumour markers. The response was monitored using tumour markers and disease progression. Well-being was assessed using the Karnofsky performance status (KPS) or that of the Eastern Cooperative Oncology Group (ECOG). RESULTS: 22% men (2/9) with a median age of 48 (31-63). The median time from being diagnosed with the metastatic disease to the start of treatment with cetuximab was 19 months (12-48). All patients had failed an irinotecan-based regime, 77.77% (7/9) had also failed one which included oxaliplatin. The median number of cycles with cetuximab was 14 (6-32). The main adverse event was the appearance of an acneiform rash in 100% of the cases. The median time until disease progression was 7 months (3-16) and 10.2 months (4-24) for overall survival. The results for well-being showed a KPS of between 80-100% and an ECOG of < 2. The results obtained in the present study for overall survival and time until disease progression are higher than those in the pivotal study (10.2 compared to 8.6 months and 7 compared to 4.1 months respectively). CONCLUSIONS: According to the results obtained, the use of assessing the EGFR expression (by the immunohistochemistry technique at least), as a means of predicting response to treatment with cetuximab may be questioned. This suggests that selecting patients using the routine assessment of this receptor is inappropriate, since it excludes patients who may potentially benefit from the treatment. However, more clinical trials are required in this area in order to confirm these conclusions.

Tratamiento con cetuximab en pacientes con cáncer colorrectal metastásico que no expresan el receptor del factor de crecimiento epidérmico / No disponible

Objetivo: Evaluar la respuesta a cetuximab en términos detiempo hasta progresión y supervivencia global en pacientes concáncer colorrectal (CCR) con determinación del receptor del factorde crecimiento epidérmico (EGFR) indetectable.Método: Se seleccionaron nueve pacientes con cetuximabEGFR negativo, confirmado mediante estudio inmunohistoquímico.Variables recogidas: datos demográficos, diagnóstico, tratamientosprevios, tiempo desde la primera metástasis hasta iniciocon cetuximab, reacciones adversas y marcadores tumorales. Larespuesta se monitorizó mediante marcadores tumorales y progresiónde la enfermedad. La evaluación de la calidad de vidamediante estado funcional de Karnofsky (KPS) o Eastern CooperativeOncology Group (ECOG).Resultados: 22% hombres (2/9) con una mediana de edadde 48 años (rango 31-63). La mediana de tiempo desde el diagnósticode enfermedad metastásica hasta inicio de tratamientocon cetuximab fue 19 meses (rango 12-48). Todos los pacienteshabían fracasado a un esquema que incluyó irinotecán, el 77,77%(7/9) también a uno con oxaliplatino. La mediana de ciclos concetuximab fue de 14 (rango 6-32). El principal efecto adverso fuela aparición de una erupción cutánea acneiforme presente en el100% de los casos. La mediana de tiempo hasta progresión fue 7(rango 3-16) meses y la supervivencia global 10,2 meses (rango 4-24). Los resultados en calidad de vida mostraron KPS entre 80-100% y ECOG < 2. Los resultados obtenidos en nuestro estudioen supervivencia global y tiempo hasta progresión son superioresa los del estudio pivotal, 10,2 vs. 8,6 meses y 7 vs. 4,1 meses respectivamente.Conclusiones: Con los resultados obtenidos se puede cuestionarla utilidad de la determinación de la expresión del EGFR, almenos mediante la técnica de inmuhistoquímica, como predictorde respuesta al tratamiento con cetuximab. Esto sugiere que laselección de los pacientes mediante la determinación rutinaria deeste receptor pudiera ser inapropiada, ya que excluye a pacientesque potencialmente pueden beneficiarse del tratamiento. No obstante,se requieren más ensayos clínicos en este ámbito que corroborenestas conclusiones

Objective: To evaluate the response to cetuximab, in terms oftime passed until disease progression and overall survival, inpatients with colorectal cancer (CRC) in which the epidermalgrowth factor receptor (EGFR) is undetectable.Method: Nine EGFR-negative patients (confirmed by animmunohistochemistry study), who were being treated with cetuximab,were selected. Variables collected: demographic data, diagnosis,previous treatments, time since first metastasis to start oftreatment with cetuximab, adverse events and tumour markers.The response was monitored using tumour markers and diseaseprogression. Well-being was assessed using the Karnofsky performancestatus (KPS) or that of the Eastern Cooperative OncologyGroup (ECOG).Results: 22% men (2/9) with a median age of 48 (31-63).The median time from being diagnosed with the metastatic diseaseto the start of treatment with cetuximab was 19 months (12-48). All patients had failed an irinotecan-based regime, 77.77%(7/9) had also failed one which included oxaliplatin. The mediannumber of cycles with cetuximab was 14 (6-32). The mainadverse event was the appearance of an acneiform rash in 100%of the cases. The median time until disease progression was 7months (3-16) and 10.2 months (4-24) for overall survival. Theresults for well-being showed a KPS of between 80-100% and anECOG of < 2. The results obtained in the present study for overallsurvival and time until disease progression are higher than thosein the pivotal study (10.2 compared to 8.6 months and 7 comparedto 4.1 months respectively). Conclusions: According to the results obtained, the use ofassessing the EGFR expression (by the immunohistochemistrytechnique at least), as a means of predicting response to treatmentwith cetuximab may be questioned. This suggests that selectingpatients using the routine assessment of this receptor is inappropriate,since it excludes patients who may potentially benefit fromthe treatment. However, more clinical trials are required in thisarea in order to confirm these conclusions