RESUMEN
Pancreatic bioengineering is a potential therapeutic alternative for type 1 diabetes (T1D) in which the pancreas is decellularized, generating an acellular extracellular matrix (ECM) scaffold, which may be reconstituted by recellularization with several cell types to generate a bioartificial pancreas. No consensus for an ideal pancreatic decellularization protocol exists. Therefore, we aimed to determine the best-suited detergent by comparing sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and Triton X-100 at different concentrations. Murine (n=12) and human pancreatic tissue from adult brain-dead donors (n=06) was harvested in accordance with Institutional Ethical Committee of the University of São Paulo Medical School (CEP-FMUSP) and decellularized under different detergent conditions. DNA content, histological analysis, and transmission and scanning electron microscopy were assessed. The most adequate condition for pancreatic decellularization was found to be 4% SDC, displaying: a) effective cell removal; b) maintenance of extracellular matrix architecture; c) proteoglycans, glycosaminoglycans (GAGs), and collagen fibers preservation. This protocol was extrapolated and successfully applied to human pancreas decellularization. The acellular ECM scaffold generated was recelullarized using human pancreatic islets primary clusters. 3D clusters were generated using 0.5×104 cells and then placed on top of acellular pancreatic slices (25 and 50 µm thickness). These clusters tended to connect to the acellular matrix, with visible cells located in the periphery of the clusters interacting with the ECM network of the bioscaffold slices and continued to produce insulin. This study provided evidence on how to improve and accelerate the pancreas decellularization process, while maintaining its architecture and extracellular structure, aiming at pancreatic bioengineering.
Asunto(s)
Ácido Desoxicólico , Detergentes , Páncreas , Dodecil Sulfato de Sodio , Ingeniería de Tejidos , Andamios del Tejido , Animales , Detergentes/química , Detergentes/farmacología , Humanos , Páncreas/citología , Ratones , Dodecil Sulfato de Sodio/farmacología , Ácido Desoxicólico/farmacología , Ácido Desoxicólico/química , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Octoxinol/química , Matriz Extracelular , Diabetes Mellitus Tipo 1 , Microscopía Electrónica de Rastreo , Matriz Extracelular Descelularizada/químicaRESUMEN
Pancreatic bioengineering is a potential therapeutic alternative for type 1 diabetes (T1D) in which the pancreas is decellularized, generating an acellular extracellular matrix (ECM) scaffold, which may be reconstituted by recellularization with several cell types to generate a bioartificial pancreas. No consensus for an ideal pancreatic decellularization protocol exists. Therefore, we aimed to determine the best-suited detergent by comparing sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and Triton X-100 at different concentrations. Murine (n=12) and human pancreatic tissue from adult brain-dead donors (n=06) was harvested in accordance with Institutional Ethical Committee of the University of São Paulo Medical School (CEP-FMUSP) and decellularized under different detergent conditions. DNA content, histological analysis, and transmission and scanning electron microscopy were assessed. The most adequate condition for pancreatic decellularization was found to be 4% SDC, displaying: a) effective cell removal; b) maintenance of extracellular matrix architecture; c) proteoglycans, glycosaminoglycans (GAGs), and collagen fibers preservation. This protocol was extrapolated and successfully applied to human pancreas decellularization. The acellular ECM scaffold generated was recelullarized using human pancreatic islets primary clusters. 3D clusters were generated using 0.5×104 cells and then placed on top of acellular pancreatic slices (25 and 50 μm thickness). These clusters tended to connect to the acellular matrix, with visible cells located in the periphery of the clusters interacting with the ECM network of the bioscaffold slices and continued to produce insulin. This study provided evidence on how to improve and accelerate the pancreas decellularization process, while maintaining its architecture and extracellular structure, aiming at pancreatic bioengineering.
RESUMEN
La diverticulitis apendicular es una enfermedad poco frecuente, con una incidencia aproximada de 1%. Se define por la presencia de divertículos verdaderos o falsos en la pared del apéndice cecal. Durante la fase aguda posee una clínica indistinguible a la apendicitis, sin embargo en ocasiones presenta características clínicas particulares que la distinguen de la apendicitis aguda, tales como la presencia de dolor abdominal insidioso o intermitente y/o ausencia de sintomatología gastrointestinal (náuseas, vómitos o anorexia). En la diverticulitis apendicular las técnicas imagenológicas son de utilidad limitada al otorgar información inespecífica, por lo que el diagnóstico tiende a realizarse mediante el estudio anatomopatológico del apéndice posterior a una intervención quirúrgica en paciente con cuadro clínico compatible con apendicitis aguda. El tratamiento de elección corresponde a la apendicectomía, lo que permite evitar complicaciones futuras como por ejemplo perforación apendicular, neoplasias, entre otros. Se obtuvieron los datos de fuentes como Pubmed y Scielo. Específicamente la búsqueda de artículos originales y de revisiones sistemáticas, preferentemente menores a 15 años de publicación en revistas científicas de alto índice de impacto, con las palabras "diverticulitis apendicular", "diverticulosis" y "complicaciones diverticulares".
Appendiceal diverticulitis is a rare disease with an incidence of approximately 1%. It is defined by the presence of true or false diverticula in the wall of the cecal appendix. During the acute phase, it has symptoms that are indistinguishable from appendicitis, however, it sometimes presents particular clinical characteristics that distinguish it from acute appendicitis, such as the presence of insidious or intermittent abdominal pain and/or the absence of gastrointestinal symptoms (nausea, vomiting, or anorexia). In appendiceal diverticulitis, imaging techniques are of limited utility as they provide non-specific information, so the diagnosis tends to be made through the pathology study of the treatment after surgery in a patient with a clinical picture compatible with acute appendicitis. The treatment of choice corresponds to appendectomy, which allows avoiding future complications such as appendiceal perforation, neoplasms, among others. Data were obtained from sources such as Pubmed and Scielo, specifically searching for original articles and systematic reviews with the words "apendicular diverticulitis", "diverticulosis" and "diverticular complications". The criteria used were articles mainly under 5 years of publication in high-impact scientific journals.
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INTRODUCTION: Pompe disease (PD) is a rare metabolic myopathy with an ample and heterogeneous clinical spectrum, particularly late onset PD (LOPD), which is characterized by appearance at older age and slower disease progression, leading to diagnostic confirmation difficulty and delay. AIM: To describe the genotype and clinical characteristics of Mexican patients with LOPD. MATERIAL AND METHODS: Clinical information from 19 Mexican patients with LOPD confirmed with enzyme activity and GAA gene analysis was reviewed. Genetic information of our population was crossed with international genetic databases. RESULTS: Median age between onset of symptoms and diagnosis was 19 years (range 2-43) and diagnostic confirmation 36 years (range 9-52). Most frequently referred symptoms were proximal axial weakness (n = 17; 89.5%), waddling gait (n = 17; 89.5%) and hyperlordosis (n = 7; 36.8%). Sixteen patients (84.2%) were evaluated with electromyography; a myopathic pattern was reported in 11 (57.8%), but only in 5 patients (26%) paraspinal muscle evaluation was included. The most pathogenic mutations in our group were c.-32-13T>G, c.1799G>A and c.1082C>T. CONCLUSIONS: Similar to other international publications, LOPD in Mexico is clinically heterogeneous; patients may delay years before diagnosis is established. Axial and proximal weakness is the most frequent clinical feature; thus, electromyography with paraspinal muscle evaluation is essential. Except for one, the mutations found in our patients have been previously reported in PD genetic databases.
TITLE: Enfermedad de Pompe de inicio tardío: análisis de una casuística de 19 pacientes mexicanos.Introducción. La enfermedad de Pompe es una miopatía metabólica rara con espectro clínico heterogéneo, especialmente la de inicio tardío, cuya sintomatología es de progresión más lenta y representa un gran reto diagnóstico. Objetivo. Describir el genotipo y las características clínicas de pacientes mexicanos con Pompe de inicio tardío (LOPD). Material y métodos. Se incluyó a 19 pacientes mexicanos con LOPD confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se evaluaron datos clínicos y se revisaron las mutaciones en bases de datos genómicas. Resultados. La mediana de edad de inicio de los síntomas fue de 19 años (rango: 2-43 años), y la edad de diagnóstico, de 36 años (rango: 9-52 años). Los síntomas más frecuentes fueron debilidad axial y proximal (n = 17; 89,5%), marcha basculante (n = 17; 89,5%) e hiperlordosis (n = 7; 36,8%). A 16 pacientes (84,2%) se les realizó electromiografía; 11 (57,8%) describieron patrón miopático y sólo en cinco pacientes (26%) se incluyó la valoración de los músculos paraespinales. Las variantes patogénicas más frecuentes en nuestra casuística fueron c.-32-13T>G, c.1799G>A y c.1082C>T. Conclusiones. Parecido a lo comunicado en publicaciones internacionales, la LOPD en México es clínicamente heterogénea; los pacientes pueden tardar años en llegar al diagnóstico. La debilidad muscular axial y proximal es el dato clínico más frecuente, por lo que la electromiografía debe incluir valoración de los músculos paraespinales. A excepción de una, las mutaciones encontradas en nuestra serie de casos se encuentran previamente descritas en las bases de datos de enfermedad de Pompe.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Enfermedades Musculares , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Humanos , México/epidemiología , Mutación , Adulto Joven , alfa-Glucosidasas/genéticaRESUMEN
In vitro modeling of neurodegenerative diseases is now possible by using patient-derived induced pluripotent stem cells (iPS). Through them, it is nowadays conceivable to obtain human neurons and glia, and study diseases cellular and molecular mechanisms, an attribute that was previously unavailable to any human condition. Amyotrophic lateral sclerosis (ALS) is one of the diseases that has gained a rapid advance with iPS technology. By differentiating motor neurons from iPS cells of ALS- patients, we are studying the mechanisms underlying ALS- disease onset and progression. Here, we introduce a cellular platform to help maintain longevity of ALS iPS-motor neurons, a cellular feature relevant for most late-onset human diseases. Long term cultures of patient-derived iPS cells might prove to be critical for the development of personalized-drugs.
Actualmente es posible modelar in vitro enfermedades neurodegenerativas humanas mediante el uso de células madre pluripotentes inducidas (iPS) derivadas del paciente. A través de ellas, es hoy concebible obtener neuronas y glía humanas, y estudiar mecanismos celulares y moleculares de enfermedades, un atributo que anteriormente no era posible para ninguna condición humana. La esclerosis lateral amiotrófica (ELA) es una de las enfermedades que se ha beneficiado con la tecnología de iPS. Al diferenciar neuronas motoras de células iPS obtenidas de pacientes con ELA, hemos iniciado estudios sobre los mecanismos que subyacen a la aparición y progresión de la enfermedad. Aquí, presentamos el desarrollo de una plataforma celular que permite extender la longevidad de las neuronas motoras derivadas de iPS, una característica relevante para la mayoría de las enfermedades humanas de inicio tardío. Los cultivos a largo plazo de células iPS provenientes de pacientes pueden ser determinantes en el desarrollo de terapias asociadas a la medicina de precisión.
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Humanos , Animales , Ratones , Células Madre Pluripotentes Inducidas/citología , Esclerosis Amiotrófica Lateral/metabolismo , Inmunohistoquímica , Línea Celular , Técnicas de Cocultivo , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/terapiaAsunto(s)
Humanos , Femenino , Embarazo , Complicaciones Cardiovasculares del Embarazo/clasificación , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Hipertensión Inducida en el Embarazo/clasificación , Hipertensión Inducida en el Embarazo/tratamiento farmacológico , Hipertensión/clasificaciónRESUMEN
Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.
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Antituberculosos/farmacocinética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Rifampin/farmacocinética , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/metabolismo , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Diabetes Mellitus Tipo 2/inmunología , Femenino , Semivida , Humanos , Interleucina-17/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Masculino , Persona de Mediana Edad , Rifampin/uso terapéutico , Tuberculosis Pulmonar/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto JovenRESUMEN
Arylamine N-acetyltransferase 2 (NAT2) metabolizes isoniazid (INH) and Single Nucleotide Polymorphisms (SNP) responsible for its activity has been reported. The aim of this study in the Mexican mestizo population was to evaluate NAT2 expression at the protein level in immune cells, as well as the distribution and frequency of six NAT2 SNPs and their association with anti-TB therapy, by measuring the plasma levels of INH and Acetyl-INH (AcINH). We performed genotyping assays of NAT2 SNPs in 40 TB patients and 121 healthy volunteers by real-time PCR. A method for detecting NAT2 in immune cells using flow cytometry was developed. Plasma concentrations of INH and AcINH were obtained by HPLC in TB patients and the Metabolic Ratio (MR) was calculated. The phenotypes obtained in the healthy volunteers were as follows; 18.87 % of subjects had the rapid acetylator phenotype, 45.45 % had the intermediate phenotype and 39.66 % exhibited the slow acetylator phenotype. In the TB patient group, 35 % of patients had the rapid acetylator phenotype, 32.5 % were intermediate and 32.5 % showed the slow acetylator phenotype. A higher expression level of NAT2 in innate immune cells from TB patients compared to those from healthy volunteers was detected (P < 0.013). In TB patients the MR showed a bimodal distribution with an antimode of 0.7, which was used as a threshold value for acetylator classification. A high correspondence between the rapid and slow acetylator phenotype with MR was demonstrated. In conclusion, the 282C>T, 341T>C, 481C>T, 590G>A, 803A>G, 857G>A SNPs of NAT2 gene provides accurate for prediction of the acetylator phenotype in Mexican mestizo population. A statistical difference was found in frequency of rapid metabolizer phenotype, which was higher in TB patients. In addition, the expression of NAT2 protein in immune cells can lead to further studies related to its functional role in the innate immune response against M. tuberculosis and other xenobiotics metabolized by this enzyme.
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Antituberculosos/administración & dosificación , Arilamina N-Acetiltransferasa/genética , Arilamina N-Acetiltransferasa/metabolismo , Isoniazida/administración & dosificación , Polimorfismo de Nucleótido Simple , Tuberculosis/tratamiento farmacológico , Adulto , Animales , Antituberculosos/sangre , Células CHO , Cricetulus , Femenino , Células HeLa , Humanos , Isoniazida/sangre , Linfocitos/metabolismo , Masculino , México/etnología , Persona de Mediana Edad , Tuberculosis/etnología , Tuberculosis/genética , Tuberculosis/metabolismo , Adulto JovenRESUMEN
SETTING: Subtherapeutic plasma isoniazid (INH) concentrations and the development of bacterial resistance may be attributed to poor quality and reduced bioavailability of fixed-dose combination (FDC) formulations. The bioavailability of INH from a generic and that of a branded FDC formulation had not been compared in the Mexican population. OBJECTIVE: To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) in comparison with a 3FDC reference with doses of 300 mg INH in 20 healthy Mexican adults, and to generate data regarding the oral relative bioavailability of the drug in this population. DESIGN: A single-dose, randomised-sequence, open-label, two-period crossover study. RESULTS: Both formulations were well tolerated. The pharmacokinetic parameters of INH showed wide inter-individual variability. The average relative bioavailability calculated for maximum serum concentration area under the concentration-time curve (AUC), AUC(0-24h) and AUC(0-∞) of the test 3FDC formulation vs. the 3FDC reference were respectively 64.84% (90%CI 56.01-75.06), 59.05% (90%CI 50.27-69.36) and 57.26% (90%CI 46.93-69.84). CONCLUSIONS: The 3FDC test and reference formulations were not bioequivalent because the 90%CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%) based on the rate and extent of absorption.
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Antituberculosos/farmacocinética , Medicamentos Genéricos/farmacocinética , Isoniazida/farmacocinética , Administración Oral , Adulto , Antituberculosos/administración & dosificación , Antituberculosos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Combinación de Medicamentos , Medicamentos Genéricos/administración & dosificación , Femenino , Semivida , Voluntarios Sanos , Humanos , Isoniazida/administración & dosificación , Isoniazida/sangre , Masculino , Tasa de Depuración Metabólica , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Equivalencia Terapéutica , Adulto JovenRESUMEN
Background: In conditions that may change red blood cell survival, such as hemodialysis, the accuracy of A1c glycosylated hemoglobin (HbA1c) to assess metabolic control can be hampered. Other glycosylated proteins such as fructosamine, could accomplish the role of HbA1c. Aim: To assess if HbA1c is a good metabolic control parameter in diabetic patients on chronic hemodialysis. To compare fructosamine, HbA1c and serial capillary glucose levels in the same patients. Material and Methods: Patients on hemodialysis three times per week were studied. Twenty one subjects with diabetes mellitus and 10 non-diabetic patients were included (70 percent were male). During a period of 14 days, fasting and post prandial capillary glucose levels were measured. Venous glucose, HbA1c and fructosamine were measured at the onset and completion of the monitoring period. Results: Diabetic patients were older than their non-diabetic counterparts (65 and 47 years respectively, p < 0.04). In diabetic and non-diabetic patients respectively, capillary blood glucose levels were 161 +/- 22 and 104 +/- 51 mg/dl, HbA1c levels were 6.8 +/- 1.2 and 5.4 +/- 0.4 percent and fructosamine levels were 282.0 +/- 126.6 and 154.6 +/- 73 umol/L. In all patients there was a positive correlation between blood glucose, HbA1c (r = 0.78 p < 0.01) and fructosamine (r = 0.52, p 0.02). There was a positive correlation between mean capillary glucose, HbA1c (r = 0.77, p < 0.01) and fructosamine (r = 0.69, p < 0.02). Among diabetic patients, the correlation coefficients between mean capillary glucose levels, HbA1c and fructosamine levels were 0.67 (p < 0.01) and 0.51 (NS), respectively. Conclusions: Among diabetic patients on hemodialysis fructosamine levels are not a better indicator of metabolic control than HbA1c.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus/sangre , Fructosamina/análisis , Hemoglobina Glucada/análisis , Diálisis Renal , Glucemia , Índice de Masa Corporal , Diabetes Mellitus/diagnóstico , Fallo Renal Crónico/sangre , Estudios ProspectivosRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Rifampicin (RIF) shows wide variability in its pharmacokinetics. The purpose of this study was to develop and validate a population pharmacokinetic model to characterize the inter- and intra-individual variability in pharmacokinetic parameters of RIF in Mexican patients. METHODS: Ninety-four patients receiving antituberculosis therapy participated in this prospective study. Plasma concentration-time data were described using a one-compartment model with lag time, absorption and first-order elimination. The potential influence of demographic and clinical characteristics of the patients, and the pharmaceutical formulation (A, B, C and D) on the pharmacokinetics parameters, was evaluated by non-linear mixed-effect modelling (nonmem). Seventy-seven additional patients participated in the validation of the model. RESULTS AND DISCUSSION: The final population pharmacokinetic model obtained was as follows: apparent clearance CL/F = 8·17 L/h (1·40 as high for males), apparent distribution volume V(d)/F = 50·1 L (1·29 as high for males), absorption rate constant K(aA) = 0·391/h, K(aB,C,D) = 2·70/h, relative bioavailability F(A) = 0·468, F(B,C,D) = 1, lag time in the absorption phase T(lag) = 0·264 h. The final model improved the precision on the parameter estimates (CL/F, V(d) /F and K(a) by 31·9%, 16·7% and 92·9%, respectively). The residual variability was 27·3%. WHAT IS NEW AND CONCLUSION: Gender was associated with changes in CL/F and V(d) /F whereas the pharmaceutical formulation was associated with changes in F and altered the K(a) . The validation data set showed that the model could be used in clinical practice for Bayesian dose adjustment of RIF in TB patients.
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Antibióticos Antituberculosos/farmacocinética , Modelos Biológicos , Rifampin/farmacocinética , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antituberculosos/administración & dosificación , Antibióticos Antituberculosos/uso terapéutico , Disponibilidad Biológica , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Dinámicas no Lineales , Estudios Prospectivos , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Factores Sexuales , Distribución Tisular , Adulto JovenRESUMEN
Alterations in plasma osmolality are related to changes in cell volume, which are the pathophysiological substrate of serious diseases. Under normal conditions sodium is the main determinant of plasma osmolality, and its homeostasis depends primarily on water balance. Hyponatremia is common in clinical practice, and is associated with morbidity and mortality by itself or in relation to its treatment. Despite this, sodium disorders are underdiagnosed, undertreated, and often handled improperly. Because multiple conditions with different treatments can be manifested through hyponatremia, the clear understanding of the pathophysiologic condition of each patient is essential for proper management. This review will discuss the pathophysiology, diagnostic approaches and current therapies of hyponatremia (AU)
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Humanos , Hiponatremia/diagnóstico , Hiponatremia/fisiopatología , Hiponatremia/terapia , Desequilibrio HidroelectrolíticoRESUMEN
Calcineurin inhibitor (CNI) immunosuppressive therapy post-liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor may solve the problem. Our objective was to evaluate renal function (RF) among liver transplant patients initially receiving CNI, among whom the patients with RDF were converted completely or partially to an mTOR inhibitor like everolimus (EVE). We performed a prospective study in liver transplant patients from 2000 to 2009. Creatinine levels and creatinine clearances (Cockroft-Gault) expressed as mean values ± standard deviations were measured pre- and postswitch for comparisons using Wilcoxon nonparametric tests. Six patients were converted fully or partially to EVE. Their mean age at the moment of introducing the new therapy was 52.2 ± 13.6 years (range = 28-60). Immunosuppression time prior to switching from CNI to EVE was 23.8 ± 26.6 months (range = 6-70). Postconversion follow-up was 25.8 ± 16.5 months (range = 8-42). All patients showed improvement in RF. The creatinine level improvement was significant (P = .03) namely, from a mean of 2.26 ± 0.49 to 1.21 ± 0.57 mg/dL. Glomerular filtration rate improved from a mean of 40 ± 15.13 to 72.60 ± 17.3 mL/min/m(2) (P = .03). Conversion from CNI to EVE improved creatinine concentrations and creatinine clearances with long-term effects free of graft rejection.
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Inmunosupresores/administración & dosificación , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Trasplante de Hígado , Sirolimus/análogos & derivados , Adulto , Biomarcadores/sangre , Inhibidores de la Calcineurina , Chile , Creatinina/sangre , Sustitución de Medicamentos , Quimioterapia Combinada , Everolimus , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Riñón/fisiopatología , Enfermedades Renales/sangre , Enfermedades Renales/fisiopatología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Sirolimus/administración & dosificación , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Factores de Tiempo , Resultado del TratamientoRESUMEN
SETTING: In a previous monitoring study of rifampicin (RMP) in tuberculosis (TB) patients treated with a generic formulation of a three-drug fixed-dose combination (3FDC), very low RMP levels were found. This led us to investigate the bioavailability of the product. OBJECTIVE: To investigate the relative bioavailability of RMP from a generic 3FDC formulation used in the Mexican health care system, in comparison to the reference product, in healthy volunteers. DESIGN: Two-period, two-sequence crossover study. RESULTS: Mean pharmacokinetic parameter values obtained for the test and reference product were respectively 3.13 ± 2.01 µg/ml and 9.95 ± 2.66 µg/ml for peak plasma concentration (C(max)), 15.51 ± 9.77 µg.h/ml and 58.03 ± 16.1 µg.h/ml for area under the concentration (AUC) time curve to the last measurable concentration (AUC(0-12h)) and 17.92 ± 10.66 and 68.43 ± 22.39 µg.h/ml for AUC up to time infinity (AUC(0-∞)). The test/reference ratio of the means (90%CI) was 25.36% (17.33-37.10) for C(max), 21.25% (14.61-30.89) for AUC(0-12h) and 22.08% (15.44-31.56) for AUC(0-∞). These results did not meet the criteria for bioequivalence. CONCLUSION: The test product displayed delayed absorption and markedly inferior RMP bioavailability in comparison to the reference product. RMP-containing generic formulations should only be used if their bioavailability has been evaluated to ensure interchangeability with the reference product and to avoid the risk of markedly inferior RMP exposure through the use of such a product.
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Antituberculosos/farmacocinética , Medicamentos Genéricos/farmacocinética , Rifampin/farmacocinética , Adulto , Antituberculosos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Método Doble Ciego , Combinación de Medicamentos , Medicamentos Genéricos/administración & dosificación , Humanos , Isoniazida/administración & dosificación , México , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Equivalencia Terapéutica , Adulto JovenRESUMEN
La pandemia de influenza del 2009 afectó a las pacientes gineco-obstétricas del Paraguay. Se incluyeron mujeres gestantes y 2 pacientes ginecológicas Los motivos de consulta fueron síntomas respiratorios, trabajo de parto y síntomas respiratorios, patologías obstétricas, patologías ginecológicas. Las principales comorbilidades fueron pre-eclampsia severa y asma. El manejo obstétrico más frecuente fue interrupción del embarazo. Todas fueron dadas de alta en buenas condiciones. Impactó en mujeres con complicaciones maternas y fetales de relevancia...
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Humanos , Complicaciones del Embarazo/epidemiología , Gripe Humana , Alphainfluenzavirus , Resultado del Embarazo , Virus de la Influenza A , Paraguay/epidemiologíaRESUMEN
OBJECTIVE: To define the pharmacokinetic behaviour of cefepime in neonates with severe nosocomial infections using a mixed effects model. PATIENTS AND METHODS: Thirty-one newborn infants were included in the study; 10 additional infants participated in the validation of the pharmacokinetic model. Cefepime CL and V were determined using an open monocompartmental model with first-order elimination. The influence of demographic and clinical characteristics on the model was evaluated. The non-linear mixed effect model (nonmem) program was used to determine the pharmacokinetic population model. RESULTS: The mean corrected gestational age for infants participating in the construction and validation of the model were 35 and 33 weeks, respectively. Factors included in the final pharmacokinetic model were body surface area (BSA) and calculated CL(CR). The final population model was CL (L/h) = 0.457 BSA (m(2)) + 0.243 CL(CR) (L/h) and V(L) = 4.12 BSA (m(2)). This model explains 33.3% of the interindividual variability for CL and 12.8% for V. This model was validated in ten neonates with nosocomial infections by assessing the predictive capacity of plasma cefepime concentrations using a priori and Bayesian strategies. CONCLUSIONS: The predictive performance of this population model for cefepime plasma concentrations was adequate for clinical purposes and can be used for individualizing cefepime therapy in newborn infants with severe infections. Cefepime plasma concentrations can be predicted based on BSA and calculated CL(CR). Cefepime therapy using a 250 mg/m(2) dose administered every 12 h is adequate to achieve plasma concentrations greater than 8 mug/mL during more than 60% of the dosing interval and is expected to be effective in the treatment of bloodstream infections caused by most gram negative organisms in newborn infants. A dose of 550 mg/m(2) would be required for the treatment of infections caused by Pseudomonas sp.
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Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Cefalosporinas/farmacocinética , Cefalosporinas/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Antibacterianos/administración & dosificación , Cefepima , Cefalosporinas/administración & dosificación , Femenino , Edad Gestacional , Humanos , Recién Nacido , Infusiones Intravenosas , Unidades de Cuidado Intensivo Neonatal , Masculino , México , Modelos Biológicos , Dinámicas no LinealesRESUMEN
INTRODUCTION: Combined liver and kidney transplantation (CLKT) is an exceptional therapeutic procedure limited to a few diseases with advanced compromise of these organs. Hyperoxaluria type I and polycystic disease are the most frequent indications. The aim of this article was to report our indications and results of CLKT in a multicenter transplantation program in Chile. MATERIAL AND METHODS: Our Excel database was reviewed to select patients who were treated with CLKT between 1993 and July 2004. RESULTS: Among 242 liver transplantations (LT) and 48 kidney transplantations (KT), 7 were CLKT, representing 2.8% of LT and 14.5% of KT. Four patients were women and 3 were male of average age 46.8 years. One patient was a child. Most frequent indications were chronic renal failure associated with terminal liver disease and polycystic disease. One patient needed liver retransplantation due to hepatic vein thrombosis. One patient had a biliary fistula and another had a urinary fistula, treated conservatively. Acute liver rejection took place in 3 cases, 1 of which required antibodies. Two patients died, 1 due to aspergillosis and the other due to vascular complications in the transplanted liver. Actuarial survival rates were 71.4% at 1 and 5 years. Chronic renal failure is not a contraindication to LT. CONCLUSION: CLKT is an acceptable option for these patients.
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Trasplante de Riñón/estadística & datos numéricos , Trasplante de Hígado/estadística & datos numéricos , Niño , Chile , Femenino , Humanos , Trasplante de Riñón/mortalidad , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Different ways have been suggested to expand donor numbers for liver transplantation. Transplantation using ABO-incompatible hepatic grafts has recently been a controversial issue due to the high risk of hyperacute rejection mediated by preformed anti-ABO antibodies. We report three patients with acute liver failure who were transplanted with ABO-incompatible livers: A to O in two patients and A to B in one case. We used pre- and posttransplant total plasma exchange, splenectomy, and triple immunosuppression. All three patients are alive; one graft was lost, probably secondary to thrombotic microangiopathy with low isohemagglutinin titers of 1:8. One patient developed acute cellular rejection that was reversed with a bolus of methylprednisolone. No antibody-mediated rejection occurred. Financial and infectious considerations have to be considered. In our series, the final liver transplantation cost was higher than average for acute liver failure. Plasmapheresis has the highest cost of all the additional procedures. ABO-incompatible liver transplantation, because of the splenectomy it requires, has been associated with more infections due to encapsulated organisms. However, with splenectomy in our three patients, none had infections due to these bacteria. In our country, we do not consider ABO-incompatible liver transplantation as a first-line option, except for highly selected patients.
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Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Fallo Hepático Agudo/cirugía , Trasplante de Hígado/métodos , Adulto , Preescolar , Chile , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
Our liver transplant program was started in 1993 in a private clinic and a public hospital. Thereafter, a rapid increase in adults and pediatric candidates for this therapeutic option lead to this analysis of results in 165 orthotopic liver transplants (OLT) in 143 patients between November 1993 and December 2002. Seventy-four OLT were performed in 66 adult patients and 91 in the pediatric group. Liver grafts came from cadaveric donors in 145 cases (74 adults and 71 children). The technique of living-related donor was utilized in 20 pediatric cases. Main indications for OLT in the adult group were HCV cirrhosis, primary biliary cirrhosis; biliary atresia and acute liver failure were the indications in pediatric patients. Retransplantation was needed for 23 patients, including 9 adults and 14 children. The most frequent causes of death were sepsis, graft primary nonfunction, and vascular complications. Actuarial survivals at 1 and 5 years were 80.7% and 72.6% for the adult group and 82% and 74.8% for the pediatric group, respectively. Our results are comparable to those published by large, experienced, international centers, with much better financial support.