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1.
Water Res ; 124: 290-297, 2017 11 01.
Article in English | MEDLINE | ID: mdl-28772141

ABSTRACT

Antibiotics-bacteria interactions depend on antibiotic concentration at the scale of bacteria. This study investigates how vancomycin penetrates into activated sludge flocs and can be sorbed on the bacteria and extracellular polymeric substances (EPS). The 3D structure of flocs was imaged using EPS autofluorescence. The green fluorescent BODIPY® FL vancomycin was introduced in a microscopic chamber containing activated sludge and penetration of vancomycin into the flocs by diffusion was observed using time-lapse microscopy. The penetration depended on the floc structure, as long and large pores could go through the whole flocs making preferential path. The antibiotic concentration into the flocs was also found to depend on the sorption rate. BODIPY® FL vancomycin was found to bind preferentially into Gram+ bacteria than on EPS. The vancomycin adsorption constant on bacteria according to the linear adsorption model, Kdbacteria was estimated to be 5 times higher (SD 2.6) than the adsorption constant on EPS KdEPS. These results suggest that antibiotic removal by sorption into wastewater treatment plants could change according to the amount of bacteria in the sludge. Moreover, antibiotic concentration at the scale of bacteria could be significantly higher than the concentration in the bulk solution and this should be taken into account when studying antibiotic activity or biodegradation.


Subject(s)
Gram-Positive Bacteria , Sewage , Vancomycin/chemistry , Water Pollutants, Chemical/chemistry , Bacteria , Flocculation , Microscopy, Confocal , Sewage/chemistry , Sewage/microbiology , Time-Lapse Imaging , Waste Disposal, Fluid
2.
Actas Urol Esp ; 40(3): 195-200, 2016 Apr.
Article in English, Spanish | MEDLINE | ID: mdl-26748843

ABSTRACT

INTRODUCTION: Microcytic carcinoma of the urinary bladder or bladder Small Cell Carcinoma (SCC) is a rare entity, characterised by an aggressive behaviour, with a poor prognosis, elevated metastatic potential, and is commonly found in older patients and in advanced disease stages. Here we present our experiences with the behaviour of the disease and the treatments applied. MATERIAL AND METHOD: This was a retrospective study on patients diagnosed with bladder SCC in our hospital between February 1992 and February 2014. We analysed the demographic and clinical characteristics of the tumour, the applied treatments and survival. We performed a descriptive statistical analysis of the median follow-up time, Overall Survival (OS) and Cancer-Specific Survival (CSS), using the SPSS statistical package v. 15.0. RESULTS: Over 22 years, 20 patients with an average age of 75 years were diagnosed with bladder SCC (2 female). The predominant symptom was macroscopic haematuria (75%). After the first transurethral resection (TUR) of the bladder and the histological diagnosis, 35% (7 patients) did not receive additional treatment, 15% (3 patients) were treated with chemoradiotherapy (CRT), 10% (2 patients) with TUR, 15% (3 patients) with chemotherapy (QT), 5% (1 patient) with TUR associated to CRT, 5% (1 patient) with radical surgery, 5% (1 patient) with radical surgery treatment followed by adjuvant CRT, 5% (1 patient) with palliative surgery (hypogastric arteriae ligation) followed by adjuvant QT and 5% (1 patient) with hemostatic radiotherapy (RT). With a median follow-up time of 13.8 months, the OS was 14.48 months (95% CI: 6.22 - 22.75) and the CSS 18.04 months (95% CI: 6.51-29.57). Only 10% (2 patients) survived till the end of the study. CONCLUSION: Microcytic carcinoma of the urinary bladder is a rare and aggressive entity commonly diagnosed in males of advanced age and in advanced disease stages. It has a poor prognosis and reduced survival. Due to its aggressiveness previous to the initial diagnosis, a cystectomy is only possible in very few cases; therefore multimodal treatment is necessary. This treatment is yet to be defined.


Subject(s)
Carcinoma, Small Cell , Urinary Bladder Neoplasms , Adult , Aged , Aged, 80 and over , Carcinoma, Small Cell/diagnosis , Carcinoma, Small Cell/therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/therapy
3.
Chem Commun (Camb) ; 52(7): 1311-26, 2016 Jan 25.
Article in English | MEDLINE | ID: mdl-26671042

ABSTRACT

Fluorescent nanodots have become increasingly prevalent in a wide variety of applications with special interest in analytical and biomedical fields. The present overview focuses on three main aspects: (i) a systematic description and reasonable classification of the most relevant types of fluorescent nanodots according to their nature, quantum confinement and crystalline structure is provided, starting with a clear distinction between semiconductor and carbon-based dots (graphene quantum dots, carbon quantum dots and carbon nanodots). A new set of abbreviations and definitions for them to avoid contradictions found in literature is also proposed; (ii) a rational classification allows the establishment of clear-cut differences and similarities among them. From a basic point of view, the origins of the photoluminescence of the different nanodots are also established, which is a relevant contribution of this overview. Additionally, the most outstanding similarities and differences in a great variety of criteria (i.e. year of discovery, synthesis, the physico-chemical characteristics like structure, nature, shape, size, quantum confinement, toxicity and solubility, the optical characteristics including the quantum yield and lifetime, limitations, applications as well as the evolution of publications) are thoroughly outlined; and (iii) finally, the promising future of fluorescent nanodots in both analytical and biomedical fields is discussed using selected examples of relevant applications.


Subject(s)
Carbon/chemistry , Nanostructures , Semiconductors , Fluorescence
4.
Arch Esp Urol ; 67(9): 764-9, 2014 Nov.
Article in English, Spanish | MEDLINE | ID: mdl-25407150

ABSTRACT

OBJECTIVES: To analyze the influence of the different pre - cystectomy factors, both clinical and pathological, in the follow up of patients with no residual tumor ( pT0) in the pathological examination of the radical cystectomy specimen as predictors of tumor recurrence. Secondly we intend to compare overall survival, disease free survival and cancer-specific survival with the rest of cystectomy patients in our series. METHODS: Between 1985 and 2010, radical cystectomy was performed in 280 patients with bladder cancer, being 41 pT0 (14.6%). We analyzed potential predictors for overall survival and disease-free survival: age, sex , number of transurethral resections of bladder tumor before cystectomy , tumor type , tumor grade, tumor stage, tumor size, number of tumors, associated Cis and previous instillations. We used univariate analysis of Cox regression. Survival analysis was performed using Kaplan - Meier curves and log-rank test. RESULTS: Mean age was 61.7 years and 37 patients were males (90.2%). Stages before cystectomy were pT1 in eight (19.5%) , pT2 in 31 (75.6%) and Cis in two (4.9 %) with tumor grade III in 37 (90.2%). Cystectomy specimens revealed the presence of papillary transitional cell carcinoma in 38 (92.7%) cases. The median number of pre-cistectomy-TURBT was one. Eleven patients (26.8%) received intravesical instillations. Six patients (14.63 %) had tumor recurrence and 10 (24.4 %) died from causes unrelated to the disease. None of the variables analyzed was statistically significant in the univariate analysis as a predictor of tumor recurrence. With a median follow up of 70 months (3-272) disease-free survival and overall survival at five years were 85.9% and 72.8% respectively. Compared to the non pT0 cystectomies in our series, pT0 had a statistically significant difference for better recurrence-free survival (63.4 % and 36.8%, respectively in pT0 and no-pT0 patients) (p〈0,05). CONCLUSIONS: According to the results, we have found a better outcome for pT0 patients after cystectomy compared to those with residual tumor. We have not found any pre - cystectomy predictive factor related to disease-free survival and overall survival.


Subject(s)
Carcinoma, Transitional Cell , Cystectomy , Urinary Bladder Neoplasms , Carcinoma, Transitional Cell/surgery , Disease-Free Survival , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Retrospective Studies , Urinary Bladder Neoplasms/surgery
5.
Arch. esp. urol. (Ed. impr.) ; 67(9): 764-769, nov. 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-129943

ABSTRACT

OBJETIVOS: Analizar la influencia de los diferentes factores pre-cistectomía tanto clínicos como anatomopatológicos, en el seguimiento de pacientes con estudio anatomopatológico de la pieza de cistectomía radical con ausencia de tumor residual (pT0), como factores predictivos de recurrencia tumoral en estos pacientes. En segundo lugar, pretendemos comparar la supervivencia global, supervivencia libre de enfermedad y la supervivencia cáncer específica con las del resto de pacientes cistectomizados de nuestra serie. MÉTODOS: Entre 1985-2010 se intervinieron 280 pacientes de cistectomía radical por causa tumoral, de los cuales 41 fueron pT0 (14,6%). Se exploraron los potenciales factores predictores para supervivencia global y supervivencia libre de enfermedad: edad, sexo, número de resecciones transuretrales de vejiga previas a la cistectomía, tipo tumoral, grado, estadio, tamaño tumoral, número de tumores, Cis asociado e instilaciones previas usando un análisis univariado de regresión de Cox. El análisis de supervivencia se realizó mediante curvas de Kaplan-Meier y Log-Rank test. RESULTADOS: La edad media fue 61,7 años y 37 (90,2%) de ellos fueron varones. Los estadios previos a la cistectomía fueron pT1 en ocho (19,5%), pT2 en 31 (75,6%), y Cis en dos (4,9%), con un grado tumoral III en 37 (90,2%). La anatomía patológica (AP), reveló la presencia de carcinoma transicional papilar en 38 (92,7%) casos. La mediana de RTU-V previas fue una. Habían recibido instilaciones endovesicales 11 (26,8%) pacientes. Seis pacientes (14,63%) presentaron recidiva tumoral y diez (24,4%) fallecieron por causas ajenas a la enfermedad. Ninguna de las variables analizadas resultó ser estadísticamente significativa en el estudio univariado como predictora de recurrencia tumoral. Con una mediana de seguimiento de 70 meses (3-272), la supervivencia libre de enfermedad y supervivencia global fueron del 85,9% y del 72,8% a los cinco años respectivamente. Comparando con las cistectomías no pT0 de nuestra serie, los pT0 presentaban una diferencia estadísticamente significativa en cuanto a mayor supervivencia libre de recurrencia (63,4% y 36,8% respectivamente en pacientes no pT0) (p<0,05). CONCLUSIONES: En nuestra serie, al análisis encontramos que los resultados clínicos de los pacientes pT0 tras la cistectomía son mejores que los de los pacientes con tumor residual. No habiendo encontrado factores pronósticos pre-cistectomía predictivos para la supervivencia libre de enfermedad


OBJETIVES: To analyze the influence of the different pre-cystectomy factors, both clinical and pathological, in the follow up of patients with no residual tumor ( pT0 ) in the pathological examination of the radical cystectomy specimen as predictors of tumor recurrence. Secondly we intend to compare overall survival, disease free survival and cancer-specific survival with the rest of cystectomy patients in our series. METHODS: Between 1985 and 2010, radical cystectomy was performed in 280 patients with bladder cancer, being 41 pT0 (14.6%). We analyzed potential predictors for overall survival and disease-free survival: age, sex , number of transurethral resections of bladder tumor before cystectomy , tumor type , tumor grade, tumor stage, tumor size, number of tumors, associated Cis and previous instillations. We used univariate analysis of Cox regression. Survival analysis was performed using Kaplan - Meier curves and log-rank test. RESULTS: Mean age was 61.7 years and 37 patients were males (90.2%). Stages before cystectomy were pT1 in eight (19.5%) , pT2 in 31 (75.6%) and Cis in two (4.9 %) with tumor grade III in 37 (90.2%). Cystectomy specimens revealed the presence of papillary transitional cell carcinoma in 38 (92.7%) cases. The median number of pre-cistectomy-TURBT was one. Eleven patients (26.8%) received intravesical instillations. Six patients (14.63 %) had tumor recurrence and 10 (24.4 %) died from causes unrelated to the disease. None of the variables analyzed was statistically significant in the univariate analysis as a predictor of tumor recurrence. With a median follow up of 70 months (3-272) disease-free survival and overall survival at five years were 85.9% and 72.8% respectively. Compared to the non pT0 cystectomies in our series, pT0 had a statistically significant difference for better recurrence-free survival (63.4 % and 36.8%, respectively in pT0 and no-pT0 patients) (p < 0,05) CONCLUSIONS: According to the results, we have found a better outcome for pT0 patients after cystectomy compared to those with residual tumor. We have not found any pre - cystectomy predictive factor related to disease-free survival and overall survival


Subject(s)
Humans , Cystectomy , Urinary Bladder Neoplasms/surgery , Postoperative Complications/epidemiology , Disease-Free Survival , Risk Adjustment/methods , Risk Factors , Retrospective Studies
6.
Endodoncia (Madr.) ; 32(2): 67-72, abr.-jun. 2014. ilus
Article in Spanish | IBECS | ID: ibc-130070

ABSTRACT

La hemisección radicular, en la actualidad, no es un tratamiento muy contemplado por el clínico; sin embargo, es una alternativa posible que debería considerarse, puesto que es un tratamiento conservador que permite mantener dientes afectados por diversas patologías periodontales o endodónticas. Este tratamiento toma especial importancia en el paciente de edad avanzada, ya que a estas edades es más frecuente la existencia de problemas que pueden empeorar el pronóstico de un diente tratado. Es importante destacar que es un tratamiento más económico que los implantes, en caso de que pueda estar indicado. Presentamos este tratamiento, y su evolución a dos años, en un paciente varón mayor de 65 años


Root hemisection, nowadays, is not really used by clinicians: however, it is a plausible alternative that must be considered, because it is a conservative treatment that allows to the clinician to maintain teeth affected by endodontic or periodontal pathologies. This treatment takes special relevance in elderly patients, because in this type of patients there are more frequent dental pathologies that could aggravate the prognosis of a treated tooth. Also we have to say that it is a more conservative treatment than other alternatives, especially extraction and implant placement. A clinical case of root hemisection is presented, in a 65 elderly man, with two years of successful evolution


Subject(s)
Humans , Male , Aged , Root Canal Therapy/methods , Crown Lengthening/methods , Ultrasonic Therapy/methods , Dental Restoration, Permanent/methods , Molar/surgery
7.
Atherosclerosis ; 231(2): 401-4, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24267258

ABSTRACT

UNLABELLED: Pilot study to validate a Computerized Decision Support Systems (CDS) (HTE-DLP) for improving treatment of hyperlipidemia. METHODS: HTE-DLP was programmed to offer automatic specific reminders for lipid treatment. Seventy-seven patients with high cardiovascular risk were randomized. 10 expert physicians in cardiovascular-risk management were recruited. We assessed number of patients at LDL <70 mg/dl after 12 weeks of treatment. RESULTS: A greater proportion of intervention group reached the LDL-C <70 mg/ml [55.0% vs 12.5%, p = 0.003; OR: 3.26 IC (1.16-9.15)]. "High potency statins" and combined therapy were used more frequently in the intervention group than the control group (p = 0.001). Seven adverse effects were documented in the intervention group and two in the control group. An acceptable relationship was observed with regard to costeffectiveness in the intervention group. Physicians expressed good agreement with HTE-DLP (86.1%) and comfortable ease-of-use (85%). CONCLUSIONS: Use of a CDSS in high-risk cardiovascular patients resulted in a significant reduction in LDL-C levels.


Subject(s)
Decision Support Systems, Clinical/economics , Dyslipidemias/therapy , Aged , Atherosclerosis/economics , Atherosclerosis/therapy , Cardiology/methods , Cardiology/standards , Cholesterol, LDL/blood , Cost-Benefit Analysis , Dyslipidemias/economics , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/economics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Pilot Projects , Treatment Outcome , Triglycerides/blood , User-Computer Interface
8.
Arch Esp Urol ; 66(1): 180-5, 2013.
Article in Spanish | MEDLINE | ID: mdl-23406814

ABSTRACT

Renal graft neoplasias are a rare complication,possibly due to the immunosuppressive therapy itself and increased susceptibility to potentially oncogenic viruses. Few case series have been reported in the literature on the treatment of such tumors, so far there is no clear consensus on how to deal with them. We conducted an exhaustive review of the literature to examine the treatment performed by different authors.


Subject(s)
Kidney Neoplasms/etiology , Kidney Neoplasms/therapy , Kidney Transplantation/adverse effects , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/etiology , Carcinoma, Renal Cell/therapy , Humans , Immunosuppressive Agents/adverse effects , Kidney Neoplasms/diagnosis , Kidney Neoplasms/surgery , Minimally Invasive Surgical Procedures
9.
Langmuir ; 26(15): 12540-7, 2010 Aug 03.
Article in English | MEDLINE | ID: mdl-20604541

ABSTRACT

Fluorescent silica and alumina-like spherical particles with almost equal sizes are synthesized. Dilute aqueous suspensions are prepared with various ratios of those colloidal particles that exhibit opposite surface charges. These suspensions undergo heteroaggregation for a wide range of compositions. The structure of the formed aggregates is analyzed by means of confocal microscopy. The experimental results are compared to those of Brownian dynamics simulations in which the interactions between colloids are modeled by the DLVO potential. Good agreement between experiments and simulations is obtained.


Subject(s)
Aluminum Oxide/chemistry , Colloids/chemistry , Silicon Dioxide/chemistry , Microscopy, Confocal , Models, Theoretical
10.
Hum Genet ; 123(4): 429-32, 2008 May.
Article in English | MEDLINE | ID: mdl-18340466

ABSTRACT

The dominant negative effect of mutations is rare in metabolic diseases and its mechanism has not been studied much. Hypophosphatasia, a bone inherited metabolic disorder, is a good model because the disease can be dominantly transmitted. The gene product activity depends on a homodimeric configuration and many mutations have been reported in the ALPL gene responsible for the disease. Using CFP/YFP-tagged-TNSALP plasmids, transfections in COS cells and confocal fluorescence analyses, we studied the point mutation G232V (c.746G>T). We showed that the G232V protein sequestrates some of the wild-type protein into the cells and prevents it from reaching the membrane where it plays its physiological role.


Subject(s)
Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Genes, Dominant , Hypophosphatasia/enzymology , Hypophosphatasia/genetics , Mutation, Missense , Alkaline Phosphatase/chemistry , Amino Acid Substitution , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , COS Cells , Chlorocebus aethiops , Female , Green Fluorescent Proteins/chemistry , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Heterozygote , Humans , Infant , Infant, Newborn , Luminescent Proteins/chemistry , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Microscopy, Fluorescence , Models, Genetic , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Subcellular Fractions/enzymology , Transfection
11.
J Chromatogr A ; 1158(1-2): 234-40, 2007 Jul 27.
Article in English | MEDLINE | ID: mdl-17395192

ABSTRACT

This article presents the state of the art of qualitative analysis in the framework of the chromatographic analysis. After establishing the differences between two main classes of qualitative analysis (analyte identification and sample classification/qualification) the particularities of instrumental qualitative analysis are commented on. Qualitative chromatographic analysis for sample classification/qualification through the so-called chromatographic fingerprint (for complex samples) or the volatiles profile (through the direct coupling headspace-mass spectrometry using the chromatograph as interface) is discussed. Next, more technical exposition of the qualitative chromatographic information is presented supported by a variety of representative examples.


Subject(s)
Chromatography/methods
12.
Bioresour Technol ; 98(18): 3561-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17196816

ABSTRACT

The biological oxidation of elemental sulphur (S(o)) added to three alkaline composts prepared with a range of organic wastes (CC, melon crop residues; MC, mixed manures; and BC, pine bark) to reduce their pH was studied. The titration curves showed that to achieve an equivalent pH drop, compost CC needed a larger dose of S(o) than did composts MC and BC. The acidification efficiency was high in the three composts (53%), but the pH reduction obtained from the titration curves in MC and BC composts was lower than expected. S(o) oxidation in amended composts was found to be related to pH and CaCO(3) content decreases, and to the rise in CaSO(4) and electrical conductivity levels. A remarkable increase in the autotrophic bacteria population and a slight increase in heterotrophic bacteria along with S(o) oxidation were recorded. Actinomycetes, fungi and yeasts were not affected by the addition of S(o) to composts.


Subject(s)
Agriculture , Soil/analysis , Sulfur/chemistry , Hydrogen-Ion Concentration , Oxidation-Reduction , Sulfur/metabolism
13.
J Chromatogr A ; 1141(1): 98-105, 2007 Feb 02.
Article in English | MEDLINE | ID: mdl-17188700

ABSTRACT

A vanguard/rearguard analytical strategy for the monitoring of the degradation of yoghurt samples is proposed. The method is based on the headspace-gas chromatography-mass spectrometry (HS-GC-MS) instrumental coupling. In this combination, the chromatographic column is firstly used as an interface between the HS and the MS (vanguard mode) avoiding separation of the volatile components by maintaining the chromatographic oven at high, constant temperature. By changing the thermal conditions of the oven, the aldehydes can be properly separated for individual identification/quantification (rearguard mode). In the vanguard method, the quantification of the volatile aldehydes was calculated through partial least square and given as a total index. The rearguard method permits the detection of the aldehydes at concentrations between 12 and 35 ng/g. Both methods were applied to the study of the environmental factors favouring the presence of the volatile aldehydes (C(5)-C(9)) in the yoghurt samples. Principal component analysis of the total concentration of aldehydes with the time (from 0 to 30 days) demonstrates the capability of the HS-MS coupling for the estimation of the quality losses of the samples. The results were corroborated by the HS-GC-MS which also indicates that pentanal was present in the yoghurt from the beginning of the study and the combination of light/oxygen was the most negative influence for sample conservation.


Subject(s)
Aldehydes/analysis , Gas Chromatography-Mass Spectrometry/methods , Yogurt/analysis , Calibration , Fluorescence , Multivariate Analysis , Principal Component Analysis , Reproducibility of Results , Time Factors , Volatilization
14.
Farm. aten. prim ; 5(1): 8-14, 2007. ilus, tab
Article in Es | IBECS | ID: ibc-057068

ABSTRACT

Objetivo. Determinar el efecto de una intervención informativa en médicos de atención primaria sobre la utilización de estatinas. Métodos. Estudio cuasi-experimental con grupo control que mide las variaciones del número de DHD (dosis diaria definida por 1.000 habitantes y día) de estatinas globalmente y por principio activo tras una intervención informativa. Dicha intervención consistió en una entrevista farmacoterapéutica centrada en el tratamiento hipolipemiante, realizada en un grupo de médicos de atención primaria cuya prescripción superaba la media del área. Resultados. Tras la intervención, el número de DHD de estatinas disminuyó en mayor medida en el grupo de intervención que en el grupo control, sobre todo en la población pensionista (–41,3 frente a –8,6). La prescripción de atorvastatina y cerivastatina se redujo en el grupo de intervención, mientras que se incrementó en el grupo control: atorvastatina: –1,3 DHD frente a 0,1 en la población activa, –14,7 frente a 4,3 en pensionistas y –5,1 frente a 0,8 en la población total; cerivastatina: –0,1 DHD frente a 0,3 en la población activa, –5 frente a 4,5 en pensionistas y –1,2 frente a 1,4 en la población total. Estas diferencias no alcanzaron significación estadística. Conclusiones. Tras la intervención, se puso de manifiesto un distinto comportamiento en la prescripción de estos fármacos entre el grupo de intervención y el grupo control, sobre todo en relación con la prescripción de nuevos fármacos. La falta de significación estadística puede ser debida a un insuficiente tamaño muestral o a un efecto de contaminación entre el grupo de intervención y el grupo control


Objective. To evaluate the effect of an informative intervention on general practitiones (GPs) about statins use criteria in primary care. Method. Cuasi experimental study with control group. Academic detaliling about treatment of hypercholesterolemia was carried out in a GPs group which prescribed statins over the mean level of the Health Department. Changes in DHDs (Defined Daily Dose /1000 inhabitants and day) after the intervention have been measured. Results. After the intervention statins DHD diminished in the intervention group (IG), mainly for pensioner patients (–41.3 in IG versus –8.6 in CG). Atorvastatin and cerivastatin prescription diminished in IG and increased in CG (atorvastatin: –1.3 in IG versus 0.1 in CG for no pensioner population, –14.7 in IG versus 4.3 in CG in pensioner population and –5.1 in IG versus 0.8 in CG for total population; cerivastatin: –0.1 in IG versus 0.3 in CG in no pensioner population, –5 in IG versus 4.5 in CG in pensioner population and –1.2 DHD in IG versus 1.4 in CG in total population). These differences were significant in global statins prescription for pensioner population and for total population. Conclusions. After this intervention, a different behaviour on statins prescription among GPs from IG and from CG has been observed, so for total statatins use as for new statins. Lack of statistical significance in some of these changes can be related to simple size or to a contamination effect of CG


Subject(s)
Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/drug therapy , Clinical Trial , Drug Prescriptions/statistics & numerical data , Hypolipidemic Agents/therapeutic use , Drug Utilization/statistics & numerical data , Primary Health Care/statistics & numerical data , Health Surveys
15.
Proc Natl Acad Sci U S A ; 103(20): 7747-52, 2006 May 16.
Article in English | MEDLINE | ID: mdl-16682638

ABSTRACT

Mice in which the Jkappa cluster was replaced with a VkappaJkappa rearranged gene were studied. More than 90% of B cells from homozygous mutant mice expressed the transgenic kappa chain but showed a slightly reduced level of kappa transcripts compared with WT B lymphocytes. Light chain inclusion was apparent in 10% of B cells from these mice and raised 25% in hemizygous mice with a still lower expression of the knockin kappa chain. Beyond the rules of clonal selection, peripheral B cells developed in such animals, with included cells being activated and differentiating into class-switched or antibody-secreting cells. The high amount of included mature B cells was associated with an increase of hybrid kappa/lambda immunoglobulins but not with the increased prevalence of autoantibodies. Altogether, these data suggest that light chain exclusion prevalent in normal B cells mostly results from ordered rearrangements and stochastic mechanisms but is neither tightly ensured by a stringent cell selection process nor absolutely required for normal B cell function.


Subject(s)
B-Lymphocytes , Cell Differentiation/physiology , Gene Rearrangement, B-Lymphocyte, Light Chain , Immunoglobulin Light Chains , Animals , Autoantibodies/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/physiology , Cell Lineage , Humans , Hybridomas/immunology , Immunoglobulin kappa-Chains/genetics , Immunoglobulin kappa-Chains/metabolism , Immunoglobulin lambda-Chains/genetics , Immunoglobulin lambda-Chains/metabolism , Mice , Mice, Transgenic , Multigene Family , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Spleen/cytology , Transgenes
16.
Life Sci ; 75(3): 313-28, 2004 Jun 04.
Article in English | MEDLINE | ID: mdl-15135652

ABSTRACT

The expression of CD34 antigen in acute myelogenous leukemias is considered an unfavourable prognosis marker for response to anticancer drugs and duration of remission. This study investigated the applicability of long-circulating immunoliposomes loaded with doxorubicin targeted to CD34 antigen present on MDR(+) human myelogenous leukemia KG-1a cell line. Immunoliposomal doxorubicin showed a higher cytotoxicity against KG-1a cells than non-targeted liposomal doxorubicin, but it did not improve over that of free drug. Although no reversal of doxorubicin resistance was found to occur through its liposomal encapsulation, a therapeutic benefit can be obtained by the selective cytotoxicity observed. Endocytosis studies demonstrated that, after binding to CD34 antigen, the immunoliposomes are not internalized by the KG-1a cells and so the cytotoxic effect might be due to drug released into the space near the cell membrane. Thus, immunotargeting of liposomal doxorubicin to CD34(+) leukemic cells may only provide an ex vivo strategy for site-selective CD34(+) leukemia cell killing.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antigens, CD34/immunology , Doxorubicin/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Antibodies, Monoclonal , Capsules , Cell Division , Cell Line, Tumor , Cell Survival/drug effects , Chemistry, Pharmaceutical , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Drug Carriers , Drug Delivery Systems , Endocytosis/drug effects , Flow Cytometry , Humans , Immunochemistry , Leukemia, Myeloid, Acute/pathology , Liposomes , Microscopy, Confocal , Particle Size
17.
Chem Phys Lipids ; 113(1-2): 97-110, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11687230

ABSTRACT

Poly(ethylene glycol)-coated liposomes were prepared with two new synthesised pegylated cholesterol (Chol) derivatives linked via carbamate bond. Poly(ethylene glycol) (PEG) was directly linked to Chol (PEG-Chol) or through a space arm of diaminebutane (PEG-L-Chol). In buffer, the physicochemical properties of PC/Chol liposomes (2/1, molar ratio) containing up to 10 mol% of pegylated Chol derivatives did not change significantly and the PEG layer at liposome surface inhibited the agglutination of biotin-liposomes induced by streptavidin. On the other hand, in serum, PEG-L-Chol seemed to reduce the interactions of liposomes with serum proteins, much more than PEG-Chol. The low steric hindrance of PEG-Chol derivative may be due to the slow conformational transition rate of the polymer, since PEG may be deeper located in the membrane. The coupling efficiency of the ligand to the functionalised amino group at the polymer end was also affected, but, its antigen-binding activity was preserved. The basic physical-chemical characteristics studied in this work are relevant to assess the application of pegylated Chol liposomes as drug delivery systems.


Subject(s)
Antibodies, Monoclonal/immunology , Cholesterol/analogs & derivatives , Cholesterol/chemistry , Liposomes/immunology , Polyethylene Glycols/chemistry , Antibodies, Monoclonal/chemistry , Antigen-Antibody Reactions/drug effects , Antigens, CD34/immunology , Blood Proteins/metabolism , Cholesterol/pharmacology , Cross-Linking Reagents/chemistry , Drug Delivery Systems , Humans , Liposomes/chemistry , Liposomes/metabolism , Permeability/drug effects , Phosphatidylethanolamines/chemistry , Phosphatidylethanolamines/pharmacology , Phospholipids/chemistry , Polyethylene Glycols/pharmacology , Protein Binding/drug effects
18.
FEBS Lett ; 498(2-3): 219-22, 2001 Jun 08.
Article in English | MEDLINE | ID: mdl-11412861

ABSTRACT

Genes encoding plant antibiotic peptides show expression patterns that are consistent with a defence role. Transgenic over-expression of defence peptide genes is potentially useful to engineer resistance of plants to relevant pathogens. Pathogen mutants that are sensitive to plant peptides in vitro have been obtained and a decrease of their virulence in planta has been observed, which is consistent with their hypothetical defence role. A similar approach has been followed to elucidate the potential direct anti-microbial role of hydrogen peroxide. Additionally, a scavenger of peroxynitrite has been used to investigate its involvement in plant defence.


Subject(s)
Anti-Bacterial Agents/metabolism , Defensins/metabolism , Hydrogen Peroxide/metabolism , Nitrates/metabolism , Plant Physiological Phenomena , Plants/microbiology , Bacterial Physiological Phenomena , Defensins/genetics , Oxidants/metabolism , Plant Leaves/metabolism , Plants/genetics , Pseudomonas/metabolism , Pseudomonas/pathogenicity , Uric Acid/pharmacology
19.
Aten Primaria ; 26(4): 245-8, 2000 Sep 15.
Article in Spanish | MEDLINE | ID: mdl-11100585

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of an intervention for decreasing hypocholesterolemic drugs prescription in patients with low cardiovascular risk profile. DESIGN: Quasi-randomized intervention study. SETTING: Public primary health care centres in the province of Valencia (Spain). PARTICIPANTS: 238 general/family practitioners from 23 primary health care centres. INTERVENTIONS: The centres were assigned to either an experimental group that received the educational intervention (individual scientific information by outreach detailing and invitation to a workshop about treatment of hypercholesterolemia in the primary care setting with the participation of an opinion leader) or a control group. MEASUREMENTS AND MAIN RESULTS: The effectiveness of the intervention was measured through the monthly mean daily defined doses (DDD) from the 4 months prior to the intervention until 5 months thereafter. Mean DDD increased along the study period in both groups, with no detectable differences between them. Similarly, there were no between-group differences after controlling the initial prescription levels using a mixed lineal model. CONCLUSIONS: The educational intervention as it was implemented was ineffective for changing overall hypocholesterolemic drug prescription in primary care. Consequently, this intervention is not justified for reducing pharmaceutical expenditure.


Subject(s)
Anticholesteremic Agents/therapeutic use , Drug Prescriptions , Health Education , Humans , Primary Health Care , Random Allocation , Risk Factors , Spain
20.
Aten. prim. (Barc., Ed. impr.) ; 26(4): 245-248, sept. 2000.
Article in Es | IBECS | ID: ibc-4261

ABSTRACT

Objetivo. Evaluar la efectividad de una intervención educativa diseñada para reducir la prescripción de hipocolesterolemiantes en pacientes de bajo riesgo cardiovascular. Diseño. Estudio de intervención con asignación cuasi-aleatoria por centros. Emplazamiento. Centros públicos de atención primaria de la provincia de Valencia. Participantes. Doscientos treinta y ocho médicos de familia/generales adscritos a 23 centros de salud y consultorios de atención primaria de la provincia de Valencia. Intervenciones. Los centros fueron asignados de forma cuasi-aleatoria, de forma que la mitad recibió la intervención (información científica proporcionada por un visitador médico en la propia consulta e invitación a un taller sobre tratamiento de la hiperlipemia en atención primaria, con intervención de líderes de opinión). La mitad restante actuó como grupo control. Mediciones y resultados principales. La efectividad se midió a partir de la media mensual de dosis diarias definidas (DDD) por facultativo desde los 4 meses anteriores a la intervención hasta 5 meses después. El número de DDD a lo largo del período aumentó tanto en el grupo control como en el experimental, sin diferencias significativas entre los 2 grupos. Tampoco se obtuvieron diferencias entre los 2 grupos al controlar las diferencias en niveles iniciales de prescripción mediante un modelo lineal mixto. Conclusiones. La intervención educativa, en las condiciones en que fue planteada, no fue efectiva para cambiar la prescripción global de hipocolesterolemiantes en atención primaria. Por tanto, no se justifica dicha intervención como método de control de gasto farmacéutico (AU)


Subject(s)
Humans , Drug Prescriptions , Risk Factors , Spain , Primary Health Care , Random Allocation , Anticholesteremic Agents , Health Education
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