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1.
J Antimicrob Chemother ; 79(7): 1683-1687, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38814812

RESUMEN

BACKGROUND: Bacteroides fragilis, an anaerobic gut bacterium and opportunistic pathogen, comprises two genetically divergent groups (or divisions) at the species level. Differences exist both in the core and accessory genomes and the beta-lactamase genes, with the cephalosporinase gene cepA represented only in division I and the carbapenemase gene cfiA only in division II. METHODS: Multidrug resistance in a clinical B. fragilis strain was examined by whole-genome sequencing. RESULTS: Strain CNM20200260 carried the antimicrobial resistance genes cepA, cfiA2, ant(6'), erm(F), mef(En2), est(T), tet(Q) and cat(A), along with 82-Phe mutation in gyrA (together with 47 amino acid changes in gyrA/B and parC/parE). bexA/B and other efflux pump genes were also observed. None of the detected insertion sequences was located upstream of cfiA2. The genome-based taxonomy coefficients (average nucleotide identity, DNA-DNA hybridization similarity and difference in genomic G + C%) with respect to genomes of the strains of B. fragilis division II and the novel species Bacteroides hominis (both cfiA-positive) met the criteria for CNM20200260 to belong to either species (>95%, >70% and <1%, respectively). No such similarity was seen with type strain NCTC 9343 or the representative genome FDAARGOS 1225 of B. fragilis (division I, cfiA-negative). Strain CNM20200260 harboured four out of nine Kyoto Encyclopedia of Genes and Genomes orthologues defined for division I and one of two defined for division II. CONCLUSIONS: This is the first description of the co-occurrence of cepA and cfiA in a Bacteroides strain, confirming the complexity of the taxonomy of this species.


Asunto(s)
Proteínas Bacterianas , Infecciones por Bacteroides , Bacteroides fragilis , Cefalosporinasa , beta-Lactamasas , Bacteroides fragilis/genética , Bacteroides fragilis/enzimología , Bacteroides fragilis/aislamiento & purificación , Bacteroides fragilis/clasificación , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Humanos , Cefalosporinasa/genética , Infecciones por Bacteroides/microbiología , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/farmacología , Genoma Bacteriano , Pruebas de Sensibilidad Microbiana , Análisis de Secuencia de ADN
2.
Infection ; 43(1): 103-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25135045

RESUMEN

The genus Janibacter comprises nine different species mainly found in the environment. Only two human infections by these microorganisms have been previously reported, one by J. melonis and another one by an undescribed Janibacter sp. Herewith we report the first human cases of infection by J. terrae in four bacteremic patients. The microorganisms were isolated from two consecutive blood cultures taken from four febrile patients with several underlying conditions. All patients were treated with antibiotics, two of them with favorable outcome. Two severely immunocompromised patients died, and one was treated with an antibiotic in vitro active against the isolate. Janibacter terrae was identified by phenotypic and 16S rDNA amplification methods. This report includes also the first data on antimicrobial susceptibility of this opportunistic pathogen. Clinical microbiologists should be aware of this microorganism which can be identified by phenotypic and molecular methods.


Asunto(s)
Actinobacteria , Bacteriemia , Infecciones por Bacterias Grampositivas , Actinobacteria/efectos de los fármacos , Actinobacteria/aislamiento & purificación , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad
3.
Eur J Clin Microbiol Infect Dis ; 31(12): 3385-96, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22855365

RESUMEN

Burkholderia spp. strains collected in Spain over a 13-year period from patients with cystic fibrosis (CF) (n = 148), non-CF patients (n = 103) and from environmental sources (n = 64) were characterised. One hundred and forty-one of the examined strains were involved in seven suspected nosocomial disease outbreaks. Strains were identified by their 16s rRNA and recA genes. Their genetic relatedness, the possession of cable pili and the B. cepacia epidemic strain marker (BCESM), and their susceptibility to antimicrobial agents were studied using pulsed-field gel electrophoresis (PFGE), cblA and esmR genes analysis, and by the E-test, respectively. The genomovar distribution for the 315 strains was as follows: B. stabilis 29.5 %, B. cepacia 14.9 %, B. multivorans 11.1 %, B. cenocepacia IIIA 9.5 %, B. vietnamiensis 3.8 %, B. cenocepacia IIIB 3.5 %, and B. ambifaria and B. pyrrocinia 0.3 % each. The genetic diversity of the B. cepacia complex (Bcc) was ample, with 57 different SpeI types, showing a genetic similarity of 36.4-96.6 %. No strain carried cblA, whereas 25 B. cenocepacia genotypes harboured BCESM (23 from patients with CF). Antimicrobial resistance rates to tobramycin (TOB; 86 %) and imipenem (IPM; 67 %) were high. The strains from patients with CF showed significantly greater resistance to piperacillin (PIP), levofloxacin (LVX) and co-trimoxazole (SXT) than those isolated from non-CF patients (p < 0.05). In conclusion, B. cenocepacia was the most prevalent genomovar found in patients with CF (19.1 %), whereas B. cepacia was the most common among non-CF patients (20.7 %). B. stabilis (47.6 %) was the most common environmental genomovar. Susceptibility to antimicrobial agents depended on genomovar status and strain origin.


Asunto(s)
Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/microbiología , Complejo Burkholderia cepacia/aislamiento & purificación , Proteínas Bacterianas/genética , Complejo Burkholderia cepacia/clasificación , Complejo Burkholderia cepacia/efectos de los fármacos , Complejo Burkholderia cepacia/genética , Infección Hospitalaria/microbiología , Fibrosis Quística/complicaciones , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado , Microbiología Ambiental , Variación Genética , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Tipificación Molecular , ARN Ribosómico 16S/genética , España/epidemiología
4.
New Microbes New Infect ; 44: 100946, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34917388

RESUMEN

Two hundred and eighty-six isolates from human clinical samples were identified between 1996 and 2019 as belonging to 8 families, 19 genera and 88 species of Actinobacteria. The most identified genera were Streptomyces (182 strains from 45 species), Actinomadura (29 strains, 5 species), Nocardiopsis (21 strains, 6 species) and Dietzia (18 strains, 5 species). The rest of the identified genera (15) contained 27 species with 36 isolates. Of the species studied, only 13/88 had been documented previously as isolates from clinical samples, and in some cases, as true pathogens. In this sense, a literature review of the species found in infections or in clinical samples without clear involvement in pathology has been carried out. Finally, the susceptibility to 8 antimicrobial agents has been studied. Streptomyces showed high resistance (80.8%) against cefotaxime and cotrimoxazole (55.5%), and no isolate resistance to amikacin and linezolid have been found. Lower percentages of resistance have been found in other genera, except in Dietzia (100% against cotrimoxazole and 44.4% against erythromycin). The greatest resistance in these genera was to cotrimoxazole (29.8) and erythromycin (27,9%), and no resistance to linezolid has been found in these genera. In Microbispora, Nonomuraea and Umezawaea, no resistant isolates have been found against any antibiotic studied. Only 3/104 isolates were resistant to amikacin in Amycolatopsis, Crossiella, and Micromonosopora. One isolate of Amycolatopsis was resistant to imipenem.

5.
Ann Oncol ; 21(9): 1891-1897, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20231299

RESUMEN

BACKGROUND: We have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, 'R-' group) or not (n = 40, 'R+' group) after ASCT. RESULTS: Patients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT. CONCLUSIONS: The addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/terapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
6.
RSC Adv ; 9(54): 31699-31707, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35527946

RESUMEN

Novel glass-ceramic optical fibers containing NaLuF4 nanocrystals doped with 0.5ErF3 and 2YbF3 (mol%) have been prepared by the rod-in-tube method and controlled crystallization. NaLuF4 nanocrystals with a size around 20 nm are obtained after heat treatment at 600 °C. Intense upconverted green and red emissions due to (2H11/2, 4S3/2) → 4I15/2 and 4F9/2 → 4I15/2 transitions, respectively, together with a blue emission due to 2H9/2 → 4I15/2 transition have been observed under excitation at 980 nm. The intensity of the green and red upconversion bands shows a nearly linear dependence on the excitation power which can be explained by saturation effects in the intermediate energy states and proves that a sensitized energy transfer upconversion process is responsible for the population of the emitting levels of Er3+ ions. The upconversion emission color changes from yellow to green by increasing the excitation power density which allows to manipulate the color output of the Er3+ emission in the glass-ceramic fibers. The tunable emission color is easily detected with the naked eye. This interesting characteristic makes these glass-ceramic fibers promising materials for photonic applications.

7.
Transplant Proc ; 50(2): 679-682, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29579887

RESUMEN

BACKGROUND: In haploidentical stem cell transplantation (SCT), the "ideal donor" selection is not performed in a standardized way according to killer cell immunoglobulin-like receptor (KIR) genotype expressed by potential donors. The aim of this study was to evaluate the relevance of KIR genotype in a series of patients submitted to haploidentical SCT in our center. METHODS: We retrospectively analyzed 30 patients that were prepared with the use of a conditioning regimen including thiotepa-busulfan-fludarabine with high doses of post-transplantation cyclophosphamide (CyPT) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis. We analyzed the impact of the KIR genotype variables (donor AA/Bx haplotype, donor B content, KIR inhibitor mismatches, and mismatching in KIR ligands in the graft-versus-host direction and the host-versus-graft direction) on overall survival, GVHD-free survival, and event-free survival. RESULTS: Statistical significance was found for the presence of mismatches on KIR ligands in the graft-versus-host direction in relation to the diagnosis of chronic GVHD (54% vs 100%; P = .004). Significance was also found for the effect of the donor presence AA or Bx haplotype in relation to the diagnosis of chronic GVHD (50% vs 86%; P = .033). CONCLUSIONS: KIR genotyping can provide useful information that can help us with the right donor choice for haploidentical SCT without T-cell depletion with high doses of CyPT. Donors with Bx haplotype that do not show KIR ligand incompatibilities in the graft-versus-host direction may provide a lower risk of GVHD.


Asunto(s)
Selección de Donante/métodos , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Receptores KIR/genética , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Genotipo , Enfermedad Injerto contra Huésped/inmunología , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Linfocitos T/inmunología , Acondicionamiento Pretrasplante , Adulto Joven
8.
Value Health ; 10(6): 466-77, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17970929

RESUMEN

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.


Asunto(s)
Estado de Salud , Calidad de Vida , Rinitis Alérgica Perenne , Rinitis Alérgica Estacional , Encuestas y Cuestionarios , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Reproducibilidad de los Resultados , España
9.
Bone Marrow Transplant ; 52(9): 1273-1279, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28604667

RESUMEN

Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index. One patient had primary graft failure and three more died before +21. The median days to neutrophil and platelet recoveries were +18 and +23, respectively, and 93% achieved a full donor chimerism on day +30. At 1 year, cumulative incidences (CumInc) of non-relapse mortality and relapse were 27 and 19%. One-year overall survival and PFS were 61 and 51%. CumInc of grade II-IV and III-IV were 23 and 14%. At 30 months, CumInc of limited and extensive GvHD were 20 and 22%. In conclusion, patients with hematological malignancies who receive an unmanipulated haploSCT with post-transplant cyclophosphamide may benefit from less intense pharmacological prophylaxis for GvHD prophylaxis. Whether this approach potentiates the graft-versus-tumor effect and decreases relapses requires further investigation.


Asunto(s)
Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Ciclofosfamida/farmacología , Femenino , Neoplasias Hematológicas/patología , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tacrolimus/farmacología , Adulto Joven
10.
New Microbes New Infect ; 19: 19-27, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28702198

RESUMEN

One hundred thirty-six isolates, 88 human and 48 environmental, that met the requirements to belong to the genus Paenibacillus were identified using a polyphasic taxonomic approach known as 16S rRNA plus phenotypic traits. Thirty-seven Paenibacillus species were identified; some had not been previously reported from clinical samples. The main species were P. pabuli (13 isolates), P. provencensis (11), P. phoenicis (9) and P. lautus (8). P. pabuli (11/13) and P. provencensis (8/11) were mainly environmental isolates, while P. phoenicis (9/9) and P. lautus (6/8) were mainly human isolates. Despite the difficulties in assigning to human Paenibacillus isolates a role as a pathogen or contaminant, here 25% of the isolates were involved in true infections, especially in those cases that affected abscesses, wound exudates, ocular infections and diverse fluids. In addition, 15 isolates were identified as 11 'Candidatus' to a new species, all of them from human specimens except one that was obtained from laboratory air. The antimicrobial susceptibility testing showed 95.6% of isolates were resistant to ampicillin, 44% were resistant to cotrimoxazole, 20 to 30% were resistant to cefotaxime and vancomycin and 13% were resistant to rifampicin and erythromycin.

11.
Bone Marrow Transplant ; 51(10): 1307-1312, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27159177

RESUMEN

Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.


Asunto(s)
Busulfano/uso terapéutico , Enfermedad de Hodgkin/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Recuperativa/métodos , Terapia Recuperativa/mortalidad , España , Análisis de Supervivencia , Trasplante Haploidéntico/efectos adversos , Trasplante Haploidéntico/mortalidad , Adulto Joven
12.
Clin Microbiol Infect ; 21(2): 150-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25658563

RESUMEN

Species of the Burkholderia cepacia complex are associated with opportunistic infection in patients with cystic fibrosis. For years now, B. multivorans and B. cenocepacia have been the most frequently isolated species within the complex in such patients. However, between 2008 and 2012, the overall incidence of these species in Spain (17.7% and 12.5% respectively) was overtaken by that of B. contaminans (36.5%). The population structure of B. contaminans isolates from Spanish patients with cystic fibrosis was analysed using multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Three major known sequence types (ST102, ST404 and ST482) and a new one (ST771) were identified among 59 isolates. In addition, PFGE detected 17 pulsotypes. Susceptibility to antibiotics was examined using the Etest. Cotrimoxazole and ceftazidime were the most active antibiotics against B. contaminans, inhibiting growth in 88% and 86% of the isolates, respectively. In addition, this species showed less resistance to most of the antibiotics tested than did either B. multivorans or B. cenocepacia isolates recovered from similar Spanish patients.


Asunto(s)
Infecciones por Burkholderia/epidemiología , Burkholderia/clasificación , Burkholderia/aislamiento & purificación , Fibrosis Quística/complicaciones , Genotipo , Neumonía Bacteriana/epidemiología , Antibacterianos/farmacología , Burkholderia/genética , Farmacorresistencia Bacteriana , Electroforesis en Gel de Campo Pulsado , Variación Genética , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Tipificación de Secuencias Multilocus , España/epidemiología
13.
Autoimmunity ; 32(2): 129-32, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11078159

RESUMEN

Anti-DNA antibodies often exhibit cross-reactivity. It has been observed that anti-DNA antibodies cross-react with A and D snRNP proteins in an in-house developed Western blot assay but do not cross-react with native U1RNP in ELISA or immunoprecipitation experiments. We have analyzed the cross-reactivity of anti-DNA antibodies to snRNP A and D in a recently developed commercial blot assay (InnoLIA, Innogenetics). In our experience anti-DNA antibodies do not cross-react with proteins A and D in this blot system. Hence this new blot system avoids the cross-reactivity problems in the assessment of antinuclear antibody specificity for both Sm and U1snRNP.


Asunto(s)
Anticuerpos Antinucleares/inmunología , Western Blotting/métodos , Ribonucleoproteína Nuclear Pequeña U1/inmunología , Especificidad de Anticuerpos , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Humanos , Lupus Eritematoso Sistémico/inmunología
14.
Anticancer Res ; 21(4A): 2703-7, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11724343

RESUMEN

BACKGROUND AND AIMS: Cisplatin is a well known cytostatic drug, with high efficiency against several solid tumours, among which ovarian cancer diagnosed during pregnancy can be included. The existence of carrier proteins in the plasma membrane of the trophoblast determines vectorial bile acid transfer across the placenta. Thus, the aim of the present work was to elucidate whether the coupling of cisplatin to a bile acid moiety, such as cholylglycinate, could endow the resulting drug, Bamet-R2, with enhanced beneficial properties; namely, the ability of the placenta to prevent the passage of the drug toward the foetal compartment. MATERIALS AND METHODS: On days 15 and 18 of gestation, pregnant rats were anaesthetised with ether and intravenous administration of 1 micromol cisplatin or Bamet-R2 was carried out. Following euthanasia on day 21 of pregnancy, samples from the placenta and maternal and foetal kidney, liver, brain, lung, heart, muscle and blood were collected and digested to measure tissue drug content by flameless atomic absorption spectroscopy of platinum. RESULTS: In addition to the beneficial properties of Bamet-R2 as regards its much lower toxicity than cisplatin, this study revealed the markedly different abilities of cisplatin and Bamet-R2 to cross the placenta, which accounts for higher accumulation of cisplatin in foetal tissues: mainly kidney, lung and heart. Moreover, the amount of drug that was found in the placenta itself was several-folds higher in animals treated with cisplatin than in those receiving Bamet-R2. CONCLUSION: The ability of the placental barrier to more efficiently protect the foetal compartment from cisplatin when the drug was coupled to cholylglycinate suggests the potential usefulness of Bamet-R2 as an alternative cytostatic drug in the treatment of certain tumours during pregnancy.


Asunto(s)
Antineoplásicos/farmacocinética , Intercambio Materno-Fetal/fisiología , Compuestos Organoplatinos/farmacocinética , Placenta/metabolismo , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacocinética , Animales , Femenino , Feto/metabolismo , Embarazo , Ratas , Distribución Tisular
15.
J Drug Target ; 9(3): 185-200, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11697204

RESUMEN

BACKGROUND/AIMS: Several members of a novel family of bile acid derivatives with cytostatic and virostatic activity have been synthesized and characterized. The aim of this work was to investigate the liver organotropism and biotransformation of two novel compounds with enhanced DNA-reactivity: Bamet-D3, in which a glycine-polyamine tandem was used as a spacer to separate the glycocholic acid moiety from the platinum(II) atom, and Bamet-UD2, in which cisplatin was directly bound to the carboxylate group of two ursodeoxycholic acid moieties. METHODS: Drug uptake and "in vitro" toxicity were investigated using rat hepatocytes in primary culture. Following i.v. administration of 0.5 mumol cisplatin, Bamet-D3 or Bamet-UD2, bile output, urinary and fecal excretion, organ distribution and pharmacokinetic parameters were determined in short-term (3 h) and long-term (14 days) experiments carried out on anaesthetized and conscious rats, respectively. Liver biotransformation was investigated by HPLC analysis of bile samples. Total platinum was measured by flameless atomic absorption spectroscopy. Using Nude mice, antitumour activity was investigated in subcutaneously implanted Hepa 1-6 mouse hepatoma cells. RESULTS: Uptake by rat hepatocytes was Bamet-UD2 (11.3 nmol/mg protein) > Bamet-D3 (5.6 nmol/mg protein) > cisplatin (2.1 pmol/mg protein). Bamet-UD2 induced "in vitro" cell toxicity, which was not observed for Bamet-D3 or cisplatin. On the contrary, no toxicity "in vivo" for Bamet-UD2 was found which was observed for cisplatin and Bamet-D3. This may be related with the fact that bile output of Bamet-UD2, which occurs with no major biotransformation, was > 10 fold higher than that of cisplatin and 3-fold higher than that of Bamet-D3, which was previously transformed into at least three different metabolites. Fecal excretion was Bamet-UD2 > Bamet-D3 > cisplatin, whereas urinary output was Bamet-D3 > cisplatin > Bamet-UD2. Accordingly, a marked liver- and a reduced kidney-vectoriality for Bamet-UD2, but not for Bamet-D3, was observed. Bamet-UD2 and cisplatin, but not Bamet-D3, were efficient in inhibiting tumour growth whereas, only Bamet-UD2 significantly prolonged survival time. CONCLUSIONS: There results indicate that Bamet-UD2 is a cisplatin-ursodeoxycholate derivative with strong antitumour activity, marked hepatobiliary organotropism, and reduced toxic side-effects as compared to the parent drug cisplatin.


Asunto(s)
Antineoplásicos/farmacocinética , Hígado/metabolismo , Compuestos Organoplatinos/farmacocinética , Ácido Ursodesoxicólico/farmacocinética , Animales , Antineoplásicos/metabolismo , Área Bajo la Curva , Bilis/efectos de los fármacos , Bilis/metabolismo , Biotransformación , Células Cultivadas , Cromatografía Líquida de Alta Presión , Semivida , Masculino , Ratones , Ratones Desnudos , Compuestos Organoplatinos/metabolismo , Ratas , Ratas Wistar , Distribución Tisular , Ácido Ursodesoxicólico/metabolismo
16.
Farm Hosp ; 28(4): 266-74, 2004.
Artículo en Español | MEDLINE | ID: mdl-15369437

RESUMEN

BACKGROUND: Standardised substitution of those drugs not included in the hospitals formulary constitutes one of several methods used to improve therapeutic efficiency, due to reduction of variability in pharmaceutical practice and prevention of potential medication errors. OBJECTIVES: To evaluate quality of drug substitution procedures in those drugs not included in the hospital's formulary. METHODS: Assessment study in a surgical hospital with 314 beds, using structural, process and outcome criteria from 1998 to 2002. RESULTS: Compliance degree for structure, process and outcome criteria were 100, 89 and 35%, respectively, while the established standards were 100%. Prevalence values for patients with substituted medication, increased from 2.9 (95%CI, 2.4-3.6) in 1998 to 11.1% (95%CI, 10.2-12.1) in 2002. Non-substituted drugs annual cost decreased from 20,199 in 1998 to 12,356 Euro in 2002. Drug substitution made by the pharmacist had an acceptance degree of 82.5%. No interchange errors were found in 126 replaced drugs. CONCLUSIONS: The development of quality programs to improve drug prescription adherence to the hospitals formulary, specially those that promote therapeutic interchange under the Pharmacy Committee guidance, are helpful strategies to make a proficient management of patients pharmacotherapy.


Asunto(s)
Formularios de Hospitales como Asunto/normas , Evaluación de Procesos y Resultados en Atención de Salud , Servicio de Farmacia en Hospital/normas , Control de Calidad , Equivalencia Terapéutica , Algoritmos , Medicamentos Genéricos , Adhesión a Directriz , Humanos , Comité Farmacéutico y Terapéutico , España
17.
QJM ; 107(11): 879-86, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24854177

RESUMEN

BACKGROUND: Some studies postulate that early dialysis initiation may increase mortality. AIM: The aim of the present study was to assess to what extent this was due to confounding by age. DESIGN: Observational retrospective cohort study. METHODS: We studied all patients starting dialysis therapy between 1 January 1995 and 31 December 2009 in our center. The following variables at dialysis initiation in end-stage renal disease (ESRD) patients were analysed: estimated glomerular filtration rate (eGFR), age, gender, diabetes mellitus, serum albumin, hemoglobin, period of dialysis initiation, history of ischemic heart disease and stroke. Multivariate Cox model was used to calculate adjusted patient survival. RESULTS: Over the last 15 years, 428 patients initiated dialysis therapy in our reference area. Median eGFR at dialysis initiation was 8.16 ml/min. In the univariate analysis, increased eGFR, age, dialysis initiation 1995-1999/2000-2004, diabetes and history of ischemic heart disease were associated (P < 0.05) with increased mortality in ESRD. Patients that started dialysis program with eGFR > 8.16 were older than those who did it with eGFR < 8.16 (66 vs. 61 years, P < 0.001). The association between mortality and eGFR in the crude multivarite Cox model was lost when the model was adjusted by age. In the multivariate Cox model, dialysis initiation period, serum albumin and history of ischemic heart disease were associated with mortality. CONCLUSION: History of ischemic heart disease, serum albumin and dialysis start before 2005 were risk factors for mortality in ESRD patients. Older age is usually associated with early dialysis initiation, so age adjustment is needed to perform studies aimed to calculate the effect of eGFR at dialysis initiation on survival.


Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Renal/mortalidad , Factores de Edad , Anciano , Métodos Epidemiológicos , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Masculino
19.
New Microbes New Infect ; 1(3): 35-40, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25356327

RESUMEN

During a 12-year period, Dermabacter hominis was isolated from 21 clinical samples belonging to 14 patients attending a tertiary hospital in León, Spain. Samples included blood cultures (14), peritoneal dialysis catheter exit sites (three), cutaneous abscesses (two), an infected vascular catheter (one) and a wound swab (one). Identification was made by API Coryne™ V2.0, Biolog™ GP2 and 16S rRNA gene amplification. Six febrile patients had positive blood cultures (one, two or three sets) and all of them were treated with teicoplanin (two patients), vancomycin, ampicillin plus gentamicin, amoxicillin/clavulanic acid and ciprofloxacin (one each). An additional patient with a single positive blood culture was not treated, the finding being considered non-significant. In the remaining seven patients the organism was isolated from a single specimen and three of them received antimicrobial treatment (ciprofloxacin, ceftriaxone plus vancomycin and amoxicillin/clavulanic acid). At least ten patients had several underlying diseases and conditions, and no direct mortality was observed in relation to the isolated organism. All isolates were susceptible to vancomycin, rifampin and linezolid. Resistance to other antibiotics varied: erythromycin (100%), clindamycin (78.5%), ciprofloxacin (21.4%) and gentamicin, quinupristin-dalfopristin, benzylpenicillin and imipenem 7.1% each. Thirteen isolates were highly resistant to daptomycin with MICs ranging from 8 to 48 (MIC90 = 32 mg/L); only one was daptomycin-sensitive (MIC = 0.19 mg/L).

20.
Acta Biomater ; 6(3): 953-61, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19671459

RESUMEN

Laser cladding by powder injection has been used to produce bioactive glass coatings on titanium alloy (Ti6Al4V) substrates. Bioactive glass compositions alternative to 45S5 Bioglass were demonstrated to exhibit a gradual wetting angle-temperature evolution and therefore a more homogeneous deposition of the coating over the substrate was achieved. Among the different compositions studied, the S520 bioactive glass showed smoother wetting angle-temperature behavior and was successfully used as precursor material to produce bioactive coatings. Coatings processed using a Nd:YAG laser presented calcium silicate crystallization at the surface, with a uniform composition along the coating cross-section, and no significant dilution of the titanium alloy was observed. These coatings maintain similar bioactivity to that of the precursor material as demonstrated by immersion in simulated body fluid.


Asunto(s)
Materiales Biocompatibles/química , Líquidos Corporales/química , Vidrio/química , Vidrio/efectos de la radiación , Rayos Láser , Ensayo de Materiales , Humectabilidad
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