RESUMEN
INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7⯱â¯0.8, 2.1⯱â¯1.2 and 1.8⯱â¯1â¯mg/dl respectively (pâ¯<â¯0.001). 56.9% of the patients (Nâ¯=â¯350) were monitored for anti-HLA antibodies. 94% (Nâ¯=â¯329) had no anti-HLA changes, while 6% (Nâ¯=â¯21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (Nâ¯=â¯9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.
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COVID-19 , Trasplante de Riñón , Nefrología , Humanos , Masculino , Persona de Mediana Edad , Femenino , Tacrolimus/uso terapéutico , Estudios Retrospectivos , Ácido Micofenólico/uso terapéutico , Prednisona , Prueba de COVID-19 , ARN Viral , SARS-CoV-2 , Inmunosupresores/uso terapéutico , Terapia de Inmunosupresión , Suero AntilinfocíticoAsunto(s)
Neoplasias de la Mama , Ácidos Grasos Omega-3 , Femenino , Humanos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos no Esterificados , Receptores de Estrógenos , Posmenopausia , Obesidad/complicaciones , Suplementos Dietéticos , Complicaciones Posoperatorias/prevención & controlRESUMEN
INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: 615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p<0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.
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To compare birth outcomes for patients receiving Expect With Me (EWM) group prenatal care or individual care only, we conducted a type 1 hybrid effectiveness-implementation trial (Detroit and Nashville, 2014-2016). Participants entered care <24 weeks gestation, had singleton pregnancy, and no prior preterm birth (N = 2402). Mean participant age was 27.1 (SD = 5.77); 49.5% were Black; 15.3% were Latina; 59.7% publicly insured. Average treatment effect of EWM compared to individual care only was estimated using augmented inverse probability weighting (AIPW). This doubly-robust analytic method produces estimates of causal association between treatment and outcome in the absence of randomization. AIPW was effective at creating equivalent groups for potential confounders. Compared to those receiving individual care only, EWM patients did significantly better on three of four primary outcomes: lower risk of infants born preterm (<37 weeks gestation; 6.4% vs. 15.1%, risk ratio (RR) 0.42, 95% Confidence Interval (CI) 0.29, 0.54), low birthweight (<2500 g; 4.3% vs. 11.6%, RR 0.37, 95% CI 0.24, 0.49), and admission to NICU (9.4% vs. 14.6%, RR 0.64, 95% CI 0.49, 0.78). There was no difference in small for gestational age (<10% percentile of weight for gestational age). EWM patients attended a mean of 5.9 group visits (SD = 2.7); 70% attended ≥5 group visits. Post-hoc analyses indicated EWM patients utilizing the integrated information technology platform had lower risk for low birthweight infants (RR 0.47, 95% CI 0.24, 0.86) than non-users. Future research is needed to understand mechanisms by which group prenatal care improves outcomes, best practices for implementation, and health systems savings. Trial registration: ClinicalTrials.govNCT02169024.
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Nacimiento Prematuro , Atención Prenatal , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Embarazo , Atención Prenatal/métodosRESUMEN
Rapid evolution of enzyme activities is often hindered by the lack of efficient and affordable methods to identify beneficial mutants. We report the development of a new growth-coupled selection method for evolving NADPH-consuming enzymes based on the recycling of this redox cofactor. The method relies on a genetically modified Escherichia coli strain, which overaccumulates NADPH. This method was applied to the engineering of a carboxylic acid reductase (CAR) for improved catalytic activities on 2-methoxybenzoate and adipate. Mutant enzymes with up to 17-fold improvement in catalytic efficiency were identified from single-site saturated mutagenesis libraries. Obtained mutants were successfully applied to whole-cell conversions of adipate into 1,6-hexanediol, a C6 monomer commonly used in polymer industry.
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NADP/metabolismo , Oxidorreductasas/metabolismo , Ingeniería de Proteínas/métodos , Adipatos/química , Adipatos/metabolismo , Dominio Catalítico , Glicoles/química , Glicoles/metabolismo , Éteres de Hidroxibenzoatos/química , Éteres de Hidroxibenzoatos/metabolismo , Cinética , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , Oxidorreductasas/química , Oxidorreductasas/genética , Salicilatos/química , Salicilatos/metabolismoRESUMEN
Rubisco is an ancient, catalytically conserved yet slow enzyme, which plays a central role in the biosphere's carbon cycle. The design of Rubiscos to increase agricultural productivity has hitherto relied on the use of in vivo selection systems, precluding the exploration of biochemical traits that are not wired to cell survival. We present a directed -in vitro- evolution platform that extracts the enzyme from its biological context to provide a new avenue for Rubisco engineering. Precambrian and extant form II Rubiscos were subjected to an ensemble of directed evolution strategies aimed at improving thermostability. The most recent ancestor of proteobacteria -dating back 2.4 billion years- was uniquely tolerant to mutagenic loading. Adaptive evolution, focused evolution and genetic drift revealed a panel of thermostable mutants, some deviating from the characteristic trade-offs in CO2-fixing speed and specificity. Our findings provide a novel approach for identifying Rubisco variants with improved catalytic evolution potential.
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Evolución Molecular Dirigida , Rhodospirillum/enzimología , Ribulosa-Bifosfato Carboxilasa/metabolismo , Secuencia de Aminoácidos , Dióxido de Carbono/metabolismo , Cinética , Modelos Moleculares , Filogenia , Conformación Proteica , Homología de SecuenciaRESUMEN
The aim of this study was to characterize Streptococcus pneumoniae serotype 19A isolates causing invasive pneumococcal disease in children, collected in Argentina between 1993 and 2014. A total of 176 isolates serotype 19A were analyzed. There was an increase in the proportion of serotype 19A isolates from 3% in 1993 to 6% in 2011, prior to the introduction of PCV13 in 2012, and from 2012 to 2014 its proportion gradually decreased. Penicillin resistance among serotype 19A isolates throughout the study period was 65.9%, but a significant increase was observed from 0% in 1993 to 87.5% in 2014. Genetic relationship of the isolates was determined by PFGE and selected strains were studied by MLST. Most of the isolates belonged to two clonal types: A (54.5%) and B (11.4%). Isolates of clonal type A were ST1131, a single locus variant of ST172 and accounted for 54% of the total collection. They were detected for the first time in our country in 1997 and most of them (93%) were penicillin non susceptible. Isolates of clonal type B were ST8121, a single locus variant of ST199, and were mainly susceptible to penicillin. These two clonal types are still in circulation and appear to be responsible for the dissemination of S. pneumoniae serotype 19A invasive isolates in our country.
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Farmacorresistencia Bacteriana Múltiple , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/clasificación , Antibacterianos/farmacología , Argentina/epidemiología , Técnicas de Tipificación Bacteriana , Preescolar , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Resistencia a las Penicilinas , Penicilinas/farmacología , Serogrupo , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunologíaRESUMEN
South Texas currently has the highest incidence of hepatocellular carcinoma (HCC) in the United States, a disease that disproportionately affects Latino populations in the region. Aflatoxin B1 (AFB1) is a potent liver carcinogen that has been shown to be present in a variety of foods in the United States, including corn and corn products. Importantly, it is a dietary risk factor contributing to a higher incidence of HCC in populations frequently consuming AFB1-contaminated diets. In a randomised double-blind placebo controlled trial, we evaluated the effects of a 3-month administration of ACCS100 (refined calcium montmorillonite clay) on serum AFB1-lysine adduct (AFB-Lys) level and serum biochemistry in 234 healthy men and women residing in Bexar and Medina counties, Texas. Participants recruited from 2012 to 2014 received either a placebo, 1.5 g or 3 g ACCS100 each day for 3 months, and no treatment during the fourth month. Adverse event rates were similar across treatment groups and no significant differences were observed for serum biochemistry and haematology parameters. Differences in levels of AFB-Lys at 1, 3 and 4 months were compared between placebo and active treatment groups. Although serum AFB-Lys levels were decreased by month 3 for both treatment groups, the low dose was the only treatment that was significant (p = 0.0005). In conclusion, the observed effect in the low-dose treatment group suggests that the use of ACCS100 may be a viable strategy to reduce dietary AFB1 bioavailability during aflatoxin outbreaks and potentially in populations chronically exposed to this carcinogen.
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Aflatoxina B1/sangre , Silicatos de Aluminio/uso terapéutico , Bentonita/uso terapéutico , Calcio/uso terapéutico , Venenos/sangre , Adulto , Aflatoxina B1/administración & dosificación , Silicatos de Aluminio/administración & dosificación , Bentonita/administración & dosificación , Bentonita/efectos adversos , Biomarcadores , Calcio/administración & dosificación , Arcilla , Método Doble Ciego , Femenino , Humanos , Masculino , Venenos/administración & dosificación , TexasRESUMEN
Nine systems were prepared containing Gelucire 50/13 and various amounts (9-18-36-45% w/w) of Lutrol F68 and F127 in the presence and in the absence of 10% w/w of olanzapine and formulated as a solid dispersion in the form of microspheres by ultrasound (US)-assisted spray congealing. Thermal analysis, using differential scanning calorimetry (DSC) and thermomicroscopy (HSM), suggested the presence of particles of reduced size of olanzapine precipitated inside the microspheres. The microspheres were also studied by means of electron microscopy (SEM) for their shape and aspect, by some image analysis parameters (fractal dimension) and using Energy-dispersive X-ray (X-EDS) and micro-Raman spectroscopy to qualitatively evaluate the composition of different points of the surface. The surface of the microspheres displayed a non-homogeneous distribution of the drug by the presence of wart-like protuberances, whose number increases as the Lutrol content of the systems increases. The same systems in the absence of US, obtained after cooling the molten mixtures, lack these structures and only a very few of them can be found. The blooming of the surface was hypothesized as related to crystallization or phase de-mixing or lipid component diffusion of the carrier mixture inside the cooling mass subjected to ultrasound vibration. Ultrasounds accelerate the physical changes concerning carriers and drug, outlining the importance of ultrasound to achieve stability for formulations of this type. The microspheres de-aggregate on contact with the dissolution medium and release the drug with a bimodal mode according to the Lutrol content.
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Benzodiazepinas/análisis , Química Farmacéutica/métodos , Grasas/análisis , Ondas de Choque de Alta Energía , Microesferas , Aceites/análisis , Polietilenglicoles/análisis , Benzodiazepinas/química , Rastreo Diferencial de Calorimetría/métodos , Grasas/química , Aceites/química , Olanzapina , Polietilenglicoles/química , Espectrometría Raman/métodosRESUMEN
The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed. The formulation of the 18 systems and the chemical form of the drug were found to strongly affect the mode of the drug release. The solubility of the chemical forms in the lipid mixture is in the following order: pyrrolidine ethanol salt â« acid > sodium salt (according to the solubility parameters), and the nature of the systems thus obtained ranges from a matrix, for mutually soluble drug/carrier pairs, to a microcapsule, for pairs wherein mutual solubility is poor. Drug release from microspheres prepared by pure lipids was primarily controlled by diffusion, whereas the release from microspheres containing stearic acid was diffusion/erosion controlled at pH 7.4.
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Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Diclofenaco/administración & dosificación , Diclofenaco/química , Portadores de Fármacos/química , Lípidos/química , Rastreo Diferencial de Calorimetría , Composición de Medicamentos , Ácidos Grasos/química , Glicerol/análogos & derivados , Calor , Microscopía , Microscopía Electrónica de Rastreo , Microesferas , Polietilenglicoles , Sales (Química) , Solubilidad , Ácidos Esteáricos/química , Propiedades de Superficie , Termografía , Ceras/químicaRESUMEN
OBJETIVO. Determinar la evolución de la resistencia a la eritromicina, el cloranfenicol, el trimetoprim-sulfametozaxol (SXT) y la vancomicina de aislamientos invasores de Streptococcus pneumoniae obtenidos de niños de 10 países de América Latina y del Caribe en seis años de vigilancia. MÉTODOS. Se analizaron 8 993 aislamientos de S. pneumoniae recuperados entre 2000 y 2005 de niños menores de 6 años con infecciones invasoras, procedentes de Argentina, Brasil, Chile, Colombia, Cuba, México, Paraguay, República Dominicana, Uruguay y Venezuela. La sensibilidad a los antibióticos se determinó mediante los métodos establecidos y estandarizados en el proyecto SIREVA. La resistencia a múltiples antibióticos se definió como la resistencia a tres o más familias de antibióticos, de los no betalactámicos analizados en este estudio o de los betalactámicos evaluados en un estudio previo en el que 37,8% de estos aislamientos presentaron sensibilidad disminuida a la penicilina. RESULTADOS. Se encontró algún grado de resistencia al SXT y la eritromicina (56,4% y 15,4% de los aislamientos estudiados, respectivamente) y 4,6% presentó alta resistencia al cloranfenicol. Todos los aislamientos fueron sensibles a la vancomicina. Se observó la mayor frecuencia de resistencia al SXT en los aislamientos de neumonía y a la eritromicina en los casos de sepsis (61,6% y 25,5%, respectivamente; P < 0,01). La mayor frecuencia de resistencia al SXT se observó en Brasil (71,9%) y a la eritromicina en México (38,2%) y Venezuela (32,9%). Los serotipos 14, 6B, 19F y 23F fueron los que más frecuentemente se asociaron con la resistencia a los antibióticos estudiados. CONCLUSIONES. Se observó una elevada y creciente frecuencia de aislamientos resistentes al SXT y la eritromicina, y una disminución en la proporción de aislamientos resistentes al cloranfenicol. Estas tendencias mostraron diferencias entre los países estudiados.
OBJECTIVE. To examine the development of resistance to erythromycin, chloramphenicol, trimethoprim-sulfamethoxazole (TMP-SMZ), and vancomycin of the invasive isolates of Streptococcus pneumoniae obtained from children in 10 Latin American/Caribbean countries during six years of surveillance. METHODS. Analysis of 8 993 isolates of S. pneumoniae recovered in 20002005 from children with invasive infections, who were less than 6 years of age, and from Argentina, Brazil, Chile, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, Uruguay, or Venezuela. Antibiotic susceptibility was determined through the methods established and standardized by the SIREVA project. Multidrug resistance was defined as: resistance to three or more antibiotics of the same class; to the non-beta-lactams analyzed by this study; or, to the beta-lactams evaluated by a previous study, in which 37.8% of these isolates showed decreased susceptibility to penicillin. RESULTS. Some degree of resistance was found to TMP-SMZ and erythromycin (56.4% and 15.4% of the isolates studied, respectively), with 4.6% highly resistant to chloramphenicol. All isolates were susceptible to vancomycin. The highest prevalence of TMP-SMZ resistance was observed in the pneumonia isolates; and that of erythromycin, in cases of sepsis (61.6% and 25.5%, respectively; P < 0.01). The highest prevalence of TMP-SMZ resistance was found in Brazil (71.9%), and that of erythromycin, in Mexico (38.2%) and Venezuela (32.9%). The 14, 6B, 19F, and 23F serotypes were most often associated with resistance to the antibiotics in the study. CONCLUSIONS. High and increasing rates of isolates resistant to TMP-SMZ and erythromycin were observed, as well as a decreasing percentage of isolates resistant to chloramphenicol. These trends highlight differences among the countries studied
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Humanos , Farmacorresistencia Bacteriana , Streptococcus pneumoniae/efectos de los fármacos , América Latina , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: To characterize the mechanism of glycopeptide resistance and to determine the genetic relatedness among strains by pulsed-field gel electrophoresis (PFGE) in vancomycin-resistant Enterococcus faecium from Argentina. MATERIALS AND METHODS: A total of 189 vancomycin-resistant single-patient isolates of Enterococcus faecium recovered between January 1997 and December 2000 from 30 hospitals in Argentina were studied. Minimum inhibitory concentrations were determined by the agar dilution method and van genes were detected by PCR. PFGE was used for molecular typing. RESULTS: All isolates except three (vanB) were of genotype vanA. For 189 vancomycin-resistant Enterococcus faecium, SmaI-PFGE indicated 35 clonal types. Most of the isolates (56%) belonged to the same clonal type 1, which was present in 19 hospitals and dominant in 17. CONCLUSIONS: The emergence of vancomycin-resistant Enterococcus faecium in Argentina seems to be related to the intra- and inter-hospital dissemination of an epidemic clone carrying the vanA element.
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Infección Hospitalaria/microbiología , Enterococcus faecium/genética , Infecciones por Bacterias Grampositivas/microbiología , Resistencia a la Vancomicina/genética , Argentina/epidemiología , Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Infección Hospitalaria/epidemiología , Electroforesis en Gel de Campo Pulsado/métodos , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/aislamiento & purificación , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología MolecularAsunto(s)
Artralgia/etiología , Trasplante de Riñón , Tenosinovitis/complicaciones , Tuberculosis Osteoarticular/complicaciones , Articulación de la Muñeca , Artralgia/diagnóstico , Biopsia con Aguja Fina , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , ARN Bacteriano/análisis , Líquido Sinovial/microbiología , Tenosinovitis/diagnóstico , Tenosinovitis/microbiología , Tuberculosis Osteoarticular/diagnóstico , Tuberculosis Osteoarticular/microbiologíaRESUMEN
Theophylline-loaded microparticles of a lipid carrier, Precirol ATO 5, were prepared by the ultrasonic spray-congealing method. The goal of the work was to investigate the effect of different concentrations and kind of colloidal silicon dioxide (Aerosil 90, 200 and 300) on the microparticle characteristics (particle size, drug loading, morphology and kinetics of release). The results showed that the introduction of Aerosil improved the drug distribution in the different particle sizes and that the mean diameter of the microparticles decreased with the viscosity of the suspension to be nebulized, especially that with Aerosil 300. Whatever the microparticles formulation is, SEM and image analysis did not reveal any remarkable difference of the microparticle shape and surface area, suggesting that other parameters could influence the dissolution behaviour. Actually, the dissolution profiles of all the formulations appeared to be closely related to the physico-chemical properties of Aerosil, especially to its gelation properties, which are a function of its specific surface area. In particular, microparticles having high concentration of Aerosil 200 and 300 approached a zero order release kinetics, while Aerosil 90 microparticles followed a first order release kinetics. Therefore, the drug release rate is controlled by the extent and rate of water absorption/swelling of the Aerosil employed. Finally, DSC, HSM, XRD and FT-IR evidenced the permanence of the drug in its original state.
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Preparaciones de Acción Retardada , Liposomas , Dióxido de Silicio/farmacología , Rastreo Diferencial de Calorimetría , Fenómenos Químicos , Química Física , Diglicéridos , Portadores de Fármacos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Excipientes , Cinética , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Teofilina/administración & dosificación , Teofilina/análisis , Ultrasonido , Difracción de Rayos XRESUMEN
The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.
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Acetaminofén/química , Composición de Medicamentos/instrumentación , Excipientes/química , Gusto , Acetaminofén/administración & dosificación , Administración Oral , Rastreo Diferencial de Calorimetría , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Aromatizantes/química , Fractales , Humanos , Técnicas In Vitro , Lactosa/química , Tamaño de la Partícula , Excipientes Farmacéuticos/química , Porosidad , Povidona/química , Solubilidad , Factores de Tiempo , Agua/químicaRESUMEN
El crecimiento producción de clorofila a, ficocianina, carotenoides y exopolisacáridos (EPS) de la cianobacteria filamentosa Anabaena sp. PCC 7120 fueron analizados en función del pH (5,5-10,5) con o sin soluciones amortiguadoras en cultivos discontinuos y en función del CO2 (0,03 y 5,0 por ciento) en cultivos semicontinuos a una tasa de renovación del 10 por ciento. El crecimiento de la cianobacteria se analizó por turbidez a 750nm y recuento celular, y la actividad fotosintética mediante uso de un electrodo de O2. Los cultivos, por triplicado, se mantuvieron con aireación constante, a 28 ñ 2ºC y con iluminación continua o fotoperíodo según el experimento. El pH y tampón utilizado influyeron en el crecimiento. El mayor crecimiento y contenido de EPS se alcanzaron, respectivamente, a pH 8,0-9,0 y 10,0. Sin embargo, los cultivos no tamponados resultaron con mayor contenido de clorofila a y ficocianina. El crecimiento, la actividad fotosintética y los carotenoides no variaron con la adición de CO2. Los cultivos semicontinuos con bajo CO2 produjeron los valores más elevados de clorofila a, ficocianina y exopolisacáridos, con 25,9 ñ 1,69, 2010 ñ 22,61 y 2286,0 ñ 42,76 µg.ml-1, respectivamente. El contenido de ficocianina y de EPS fue de 2,7 y 4 veces superior al obtenido a altos niveles de CO2. El pH y el sistema semicontinuo constituyen herramientas importantes para modular el crecimiento y contenido de pigmentos y de EPS de Anabaena sp. PCC 7120
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Anabaena , Carotenoides , Clorofila , Concentración de Iones de Hidrógeno , Ficocianina , Pigmentos Biológicos , Ciencia , VenezuelaRESUMEN
In this paper we prepared and characterized improved release granulates containing Piroxicam and beta-cyclodextrins (1:2.5 molar ratio), obtained by steam-aided granulation, using a one-step rotogranulator, Rotolab. These granulates were compared to those prepared by traditional wet granulation, to the physical mixture, and to the kneaded and dry granulates. The experimental data showed a significant reduction of the water amount required (50%) and of the working time, with respect to traditional wet granulation. The samples examined by scanning electron microscopy and fractal analysis revealed morphological differences related to the method of preparation: the steam-granulated material showed a diffuse porosity, as confirmed by the porosity test. Differential scanning calorimetry, infrared and X-ray analysis revealed the absence of polymorphs in the solid state of the drug. The results of the dissolution tests suggest that the steam-aided granulation may be considered a useful method to improve the in vitro dissolution rate of Piroxicam, enabling also a considerable reduction in the processing time.
Asunto(s)
Piroxicam/química , Vapor , beta-Ciclodextrinas , Química Farmacéutica , Ciclodextrinas/química , Tamaño de la Partícula , Solubilidad , Tecnología Farmacéutica/métodosRESUMEN
The aim of this study was to prepare, by melt granulation, granules containing ibuprofen as a poorly water soluble model drug in order to improve its dissolution rate and its availability; lactose as a diluent and poloxamer 188 (Lutrol F68), as a new meltable hydrophilic binder, were used. The granules were prepared in a laboratory-scale high-shear mixer, using a jacket temperature of 50 degrees C and an impeller speed of 500 rpm. The particle size analysis shows that the main fraction was between 200 and 500 microm, while the determination of drug content indicated that ibuprofen was quite uniformly distributed in all the fractions. Scanning Electron Microscopy (SEM), image and fractal analysis revealed that the granules did not have a perfect spherical shape and a rugged surface (D(s)=2.6475). The in vitro dissolution tests showed an increase in the dissolution rate of granules compared to pure drug and physical mixture. The characterisation of the samples, performed by Differential Scanning Calorimetry (DSC) and X-ray powder diffraction (XRD), suggests that the improvement of dissolution rate could be correlated to the formation of a eutectic mixture between the drug and the binder. Stability studies indicated that the granule properties do not change, at least after 1 year of storage at 25 degrees C. In conclusion, the results of this work suggest that the melt granulation technique is an easy and fast method to improve the dissolution rate of ibuprofen, using poloxamer 188 as a new hydrophilic meltable binder.