RESUMEN
BACKGROUND: Pediatric actinomycosis studies are limited to case reports or small case series. In this retrospective cohort study, we aimed to describe characteristics of skin and soft tissue actinomycosis in adolescents and children. METHODS: We conducted the study from January 2019 to December 2022, including patients ≤21 years of age with at least 1-year follow-up data. All clinical cultures obtained under sterile conditions with Actinomyces growth were included. RESULTS: One hundred four patients met inclusion criteria; median age 19 (interquartile range: 17-20) years, 68.3% female, 46.2% Black and 47.1% Hispanic. The median antibiotic treatment duration was 10 (7-10) days, and majority of patients received treatment with non-first-line Actinomyces antibiotics. Infectious disease consultation was requested for only 7 patients during their initial skin and soft tissue actinomycosis treatment. One-third of the patients with skin and soft tissue actinomycosis had documented recurrence within a median of 10 (interquartile range: 6-16) months of the initial episode. Monobacterial culture growth (85.7% vs. 63.8%, P = 0.02), patients with body mass index >25 (75% vs. 52.6%, P = 0.04) and patients with prior abscess in the same area (18.8% vs. 51.4%, P = 0.001) were significantly higher in patients with recurrent actinomycosis compared to the nonrecurrent group. In a univariate logistic regression model, they were found to be significantly associated with recurrence; monobacterial growth [odds ratio (OR): 3.4; 95% confidence interval (CI): 1.2-9.9], body mass index >25 (OR: 2.7; 95% CI, 1.1-7.0) and prior abscess (OR: 4.6; 95% CI: 1.9-11.2). CONCLUSIONS: Our study results highlight the importance of considering Actinomyces species in skin and soft tissue infections, especially in recurrent ones, and risk factors for recurrence. Suboptimal antibiotic utilization, very low numbers of consultations with infectious diseases and high recurrence rate suggest that providers should be informed and updated regarding this rare but hard-to-treat infection.
Asunto(s)
Actinomyces , Actinomicosis , Antibacterianos , Infecciones de los Tejidos Blandos , Humanos , Adolescente , Femenino , Masculino , Actinomicosis/tratamiento farmacológico , Actinomicosis/microbiología , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Niño , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/epidemiología , Actinomyces/aislamiento & purificación , Adulto Joven , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/epidemiología , Recurrencia , PreescolarRESUMEN
Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer. SENTI-101 has extended half-life, reduced systemic distribution, and improved antitumor activity when compared with recombinant cytokines, suggesting that it is more effective and has lower risk of systemic immunotoxicities. Treatment of tumor-bearing immune-competent mice with a murine surrogate of SENTI-101 (mSENTI-101) results in a potent and localized immune response consistent with increased number and activation of antigen presenting cells, T cells and B cells, which leads to antitumor response and memory-induced long-term immunity. Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in antitumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer.Graphical abstract: SENTI-101 schematic and mechanism of actionSENTI-101 is a novel cell-based immunotherapeutic consisting of bone marrow-derived mesenchymal stromal cells (BM-MSC) engineered to express IL12 and IL21 intended for the treatment of peritoneal carcinomatosis including high-grade serous ovarian cancer. Upon intraperitoneal administration, SENTI-101 homes to peritoneal solid tumors and secretes IL12 and IL21 in a localized and sustained fashion. The expression of these two potent cytokines drives tumor infiltration and engagement of multiple components of the immune system: antigen-presenting cells, T cells, and B cells, resulting in durable antitumor immunity in preclinical models of cancer.
Asunto(s)
Interleucina-12/metabolismo , Interleucinas/metabolismo , Melanoma Experimental/inmunología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Neoplasias/inmunología , Neoplasias Peritoneales/inmunología , Animales , Apoptosis , Proliferación Celular , Femenino , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Melanoma Experimental/terapia , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We present a case of a 36-year-old female who came into the emergency department with right-side abdominal pain. She went to the operating room for a diagnostic laparoscopy and appendectomy. She received intravenous (IV) acetaminophen every six hours both preoperatively and postoperatively for pain control. The patient's aspartate aminotransferase and alanine aminotransferase levels were elevated and peaked at 4,833 and 6,600 IU/L, respectively, from baselines of 14 and 15, respectively, while she was receiving 16 doses of IV acetaminophen. The patient was transferred to a regional liver transplant center for evaluation for a transplant. She was treated with IV N-acetylcysteine and discharged with a normal liver-function test without a transplant. This case report supports the possibility of hepatotoxicity associated with IV acetaminophen.
RESUMEN
We present a review of our experience and pregnancy outcome in patients with GSD III managed by our centre. Between 1997 and 2010 there were 15 pregnancies in seven women with GSD III. Four women had GSD IIIb (nine pregnancies) and three GSD IIIa (six pregnancies). There was a successful outcome in all 15 pregnancies with delivery of 15 liveborn infants. Four infants were of low birthweight (<2nd centile) but all have developed normally apart from one with behavioural/psychiatric problems. Three women had pre-existing cardiomyopathy prior to pregnancy. One of these women had deterioration of her cardiomyopathy during pregnancy and again in the post-partum period. Women with GSD III do not seem to have any issues with fertility. Overall the outcome of pregnancy for both mother and child is good. Care needs to be taken to avoid maternal hypoglycemia which may be associated with intrauterine growth restriction and low birth weight. Cardiac function should be monitored carefully particularly in those with pre-existing cardiomyopathy.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo III/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo III/terapia , Complicaciones del Embarazo/terapia , Resultado del Embarazo , Adulto , Manejo de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
The ability to culture cells in three dimensional extracellular matrix (3D ECM) has proven to be an important tool for laboratory biology. Here, we demonstrate a microfluidic perfusion array on a 96-well plate format capable of long term 3D ECM culture within biomimetic microchambers. The array consists of 32 independent flow units, each with a 4 µl open-top culture chamber, and 350 µl inlet and outlet wells. Perfusion is generated using gravity and surface tension forces, allowing the array to be operated without any external pumps. MCF-10A mammary epithelial cells cultured in Matrigel in the microfluidic array exhibit acinus morphology over 9 days consistent with previous literature. We further demonstrated the application of the microfluidic array for in vitro anti-cancer drug screening.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Células Epiteliales/citología , Glándulas Mamarias Humanas/citología , Técnicas Analíticas Microfluídicas/instrumentación , Microfluídica/instrumentación , Microtecnología/instrumentación , Línea Celular Tumoral , Diseño de Equipo , Femenino , Humanos , Técnicas Analíticas Microfluídicas/métodos , Perfusión/métodosRESUMEN
Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched-chain α-keto acid dehydrogenase complex gene. Patients generally present early in life with a toxic encephalopathy because of the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and the corresponding ketoacids. Movement disorders in maple syrup urine disease have typically been described during decompensation episodes or at presentation in the context of a toxic encephalopathy, with complete resolution after appropriate dietary treatment. Movement disorders in patients surviving childhood are not well documented. We assessed 17 adult patients with maple syrup urine disease (mean age, 27.5 years) with a special focus on movement disorders. Twelve (70.6%) had a movement disorder on clinical examination, mainly tremor and dystonia or a combination of both. Parkinsonism and simple motor tics were also observed. Pyramidal signs were present in 11 patients (64.7%), and a spastic-dystonic gait was observed in 6 patients (35.2%). In summary, movement disorders are common in treated adult patients with maple syrup urine disease, and careful neurological examination is advisable to identify those who may benefit from specific therapy. © 2011 Movement Disorder Society.
Asunto(s)
Enfermedad de la Orina de Jarabe de Arce/epidemiología , Trastornos del Movimiento/epidemiología , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Distonía/diagnóstico , Distonía/epidemiología , Femenino , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/epidemiología , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico , Examen Neurológico , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/epidemiología , Prevalencia , Temblor/diagnóstico , Temblor/epidemiología , Adulto JovenRESUMEN
Long-term follow-up studies of individuals with galactosaemia have indicated that despite a strict galactose-free diet, cognitive functioning is often below average. This study was designed to examine the neuropsychological profile of individuals with galactosaemia in terms of IQ, memory, executive functioning, perceptual abilities and educational outcome. Twenty-eight people with classic galactosaemia and no comorbid neurological or psychiatric disorder took part. A battery of clinical neuropsychological tests was performed. Overall, findings were consistent with previous literature in showing galactosaemia to be linked to below-average functioning across a range of cognitive measures when mean scores were examined. Thus, the mean overall scores for verbal and performance IQ, memory, and executive functions were in the low average range. However, a range of ability was represented across individuals, with some achieving average or above scores and education to A level or above. Further work using longitudinal methodology is needed to address the issue of factors mediating any cognitive weaknesses and to establish the extent of any possible decline in functioning over time.
Asunto(s)
Cognición , Galactosemias/psicología , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Evaluación Educacional , Escolaridad , Función Ejecutiva , Femenino , Humanos , Inteligencia , Pruebas de Inteligencia , Londres , Masculino , Memoria , Persona de Mediana Edad , Pruebas Neuropsicológicas , Percepción , Factores Sexuales , Adulto JovenRESUMEN
Patients with type Ia glycogen storage disease (GSD) have been surviving well into adulthood since continuous glucose therapy was introduced in the 1970s, and there have been many documented successful pregnancies in women with this condition. Historically, few individuals with type Ib GSD, however, survived into adulthood prior to the introduction of granulocyte colony stimulating factor (G-CSF) in the late 1980s. There are no previously published reports of pregnancies in GSD type Ib. In this case report we describe the course and management of five successful pregnancies in three patients with GSD type Ib. Patient 1 experienced an increase in glucose requirement in all three of her pregnancies, starting from the second trimester onwards. There were no major complications related to neutropenia except for oral ulcers. The infants did well, except for respiratory distress in two of them at birth. Patient 2 used cornstarch to maintain euglycemia, but precise dosing was not part of her regimen, and, hence, an increase in metabolic demands was difficult to demonstrate. She developed a renal calculus and urinary tract infection during her pregnancy and had chronic iron deficiency anemia but no neutropenia. The neonate did well after delivery. Patient 3 had poor follow-up during pregnancy. Increasing glucose requirements, worsening lipid profile, neutropenia associated with multiple infections, and anemia were noted. The newborn infant did well after delivery. In addition to the case reports, the challenges of the usage of G-CSF, the treatment of enterocolitis, and comparisons with the management of GSD Ia are discussed.
Asunto(s)
Glucosa/administración & dosificación , Enfermedad del Almacenamiento de Glucógeno Tipo I/terapia , Nacimiento Vivo , Atención Perinatal , Complicaciones del Embarazo/terapia , Almidón/administración & dosificación , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Vías de Administración de Medicamentos , Esquema de Medicación , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Humanos , Lípidos/sangre , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/genética , Sobrevivientes , Factores de Tiempo , Resultado del TratamientoRESUMEN
We present a microfluidic system for time-lapsed, live cell microscopy with the ability to control solution exchange via a dynamic flow controller. The application specific microfluidic plates are designed to maintain adherent and non-adherent cell types for multiple days with continuous medium perfusion. Upstream channels with flow controlled via custom software allow the delivery of unique exposure profiles to the cultured cells, such as square waves, step functions, ramps, etc.
Asunto(s)
Microfluídica/instrumentación , Microscopía/instrumentación , Células HeLa , HumanosRESUMEN
BACKGROUND: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. OBJECTIVE: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. DESIGN: This was a randomized, 2-d, double-blinded, crossover pilot study comparing the commonly used uncooked cornstarch with the experimental starch in 12 subjects (6 GSDIa, 6 GSDIb) aged >or=13 y. At 2200, the subjects were given 100 g of digestible starch, and glucose and lactate were measured hourly until the subject's plasma glucose concentration reached 60 mg/dL or until the subject had fasted for 10 h. The order in which the products were tested was randomized in a blinded fashion. RESULTS: The matched-pair Gehan rank test for censored survival was used to compare the therapies. The experimental starch maintained blood glucose concentrations significantly longer than did the traditional therapy (P = 0.013) in the 2-sided analysis. Most of the benefit was found to be after glucose concentrations fell below 70 mg/dL. The currently used cornstarch resulted in higher peak glucose concentrations and a more rapid rate of fall than did the new starch. CONCLUSIONS: The experimental starch was superior to standard therapy in preventing hypoglycemia (Asunto(s)
Glucemia/metabolismo
, Ayuno/sangre
, Enfermedad del Almacenamiento de Glucógeno Tipo I/dietoterapia
, Hipoglucemia/prevención & control
, Almidón/metabolismo
, Almidón/farmacología
, Adolescente
, Estudios Cruzados
, Relación Dosis-Respuesta a Droga
, Método Doble Ciego
, Femenino
, Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre
, Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo
, Humanos
, Masculino
, Proyectos Piloto
, Seguridad
RESUMEN
BACKGROUND: Developmental delay in the offspring of women with phenylketonuria (PKU) can be prevented by maintaining maternal blood phenylalanine (Phe) within a target range (100-250 micromol/L). OBJECTIVE: We aimed to analyze outcomes in the offspring of women with PKU during pregnancy and to identify prognostic factors. DESIGN: Occipitofrontal circumference at birth (OFC-B); developmental scores [developmental quotient (DQ) and intelligence quotient (IQ)]at 1, 4, 8, and 14 y; and the time of starting a Phe-restricted diet (before or after conception) were collected. The influence of maternal Phe concentrations during pregnancy on offspring outcomes also was assessed. RESULTS: The study included 105 children born to 67 mothers with PKU. Mean (+/-SD) OFC-B z scores did not differ between the preconception and postconception diet groups (0.42 +/- 1.24 and -0.96 +/- 1.19, respectively). DQ at 1 y and IQ at 8 y were higher in offspring from the preconception diet group than in offspring from the postconception diet group [DQ: 107 +/- 13.8 and 99.3 +/- 13.3, respectively (P = 0.014); IQ: 110.6 +/- 14.8 and 91.2 +/- 23.9, respectively (P = 0.005)]. Maternal Phe concentrations correlated negatively with DQ and IQ scores, and variations (SD) in all maternal blood Phe correlated negatively with 4-, 8-, and 14-y IQ scores (r = -0.385, -0.433, and -0.712; P = 0.002, 0.008, and 0.031, respectively), even when concentrations were consistently within the target range. CONCLUSIONS: The study suggests that women with PKU should start a Phe-restricted diet before conception. Maintenance of maternal blood Phe within the target range predicts good offspring outcomes, but variations even within that range should be avoided.
Asunto(s)
Discapacidades del Desarrollo/epidemiología , Fenilalanina/sangre , Fenilcetonuria Materna/fisiopatología , Complicaciones del Embarazo/fisiopatología , Peso Corporal , Discapacidades del Desarrollo/genética , Femenino , Humanos , Recién Nacido , Discapacidades para el Aprendizaje/genética , Microcefalia/genética , Fenilcetonuria Materna/genética , Embarazo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: We compared the frequency of a binary endocardial appearance in patients with hypertrophic cardiomyopathy (HCM) and Anderson-Fabry disease (AFD). BACKGROUND: A recent study suggested that a binary endocardial appearance is a highly sensitive and specific discriminator of AFD from other causes of hypertrophic cardiomyopathy (HCM). METHODS: Fourteen patients with AFD (55.4 +/- 9.9 years, 9 men) and 14 patients with HCM (57.2 +/- 10.9 years, 9 men) were randomly selected from a dedicated patient database. Two-dimensional echo images were blindly reviewed by 2 experienced echocardiographers. RESULTS: Maximum left ventricular (LV) wall thickness, LV end-systolic dimension, fractional shortening, and left atrial size were similar in the 2 patient groups. The LV end-diastolic dimension was smaller in patients with HCM (p = 0.04). A binary sign was present in 8 of 28 patients (29%). The sensitivity and specificity of the binary sign as a discriminator of AFD from HCM were 35% and 79%, respectively. A binary sign was present in only 1 patient with LV wall thickness <15 mm. CONCLUSIONS: The binary endocardial appearance lacks sufficient sensitivity and specificity to be used as an echocardiographic screening tool.
Asunto(s)
Cardiomiopatía Hipertrófica Familiar/diagnóstico por imagen , Endocardio/diagnóstico por imagen , Enfermedad de Fabry/diagnóstico por imagen , Adulto , Anciano , Diagnóstico Diferencial , Método Doble Ciego , Ecocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Non-heritable factors may have an influence on the clinical expression of monogenic inherited metabolic diseases. CASE PRESENTATION: This is a case report of a man whose mother had been diagnosed late in childhood with pyridoxine responsive homocystinuria with lens dislocation and neurodevelopmental delay. These severe complications were not observed in her son who was pyridoxine unresponsive but who had been treated appropriately since early infancy. CONCLUSION: The phenotype of people with homocystinuria can be discordant within a family, with variability in metabolic and clinical expression depending upon both the genotype and therapeutic interventions. Offspring of people with homocystinuria should be screened in early infancy and, if positive, treated appropriately whether they have pyridoxine responsive or unresponsive disease.
Asunto(s)
Citrulinemia/genética , Proteínas de Transporte de Membrana/genética , Proteínas Mitocondriales/genética , Mutación Puntual , Adulto , Ácido Aspártico/metabolismo , Transporte Biológico Activo , Citrulinemia/complicaciones , Citrulinemia/metabolismo , Europa (Continente) , Resultado Fatal , Ácido Glutámico/metabolismo , Humanos , Hiperamonemia/etiología , Hígado/metabolismo , Masculino , Proteínas de Transporte de Membrana Mitocondrial , Análisis de Secuencia de ADNRESUMEN
The investigation of cellular processes and gene regulatory networks within living cells requires the development of improved technology for dynamic, single cell imaging. Here, we demonstrate a microfluidic system capable of mechanical trapping of yeast cells with continuous flow and flow switching capability during time-lapse high magnification fluorescence imaging. The novel functionality of the system was validated by observing the response of pheromone-induced expression of GFP in Saccharomyces cerevisiae.
Asunto(s)
Microfluídica/métodos , Saccharomyces cerevisiae/citología , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de la Membrana , Proteínas Recombinantes de Fusión/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
We present a microfluidic bioreactor for culturing high-density arrays of hepatocytes in a tissue-like micro-architecture. The microfluidic environment mimicked physiological liver mass transport, enabling sustained culture of high density cells (>2,000 cells/mm(2)) without nutrient limitation for over 1 week. The key feature of this design was a microporous microfluidic barrier that formed a sieved-pocket to concentrate cells during loading. Nutrient depletion within the cell mass was avoided by maintaining a continuous flow of medium (10 microl/day) that diffused across the porous barrier. Human hepatoma cells (HepG2/C3A) remained viable and functional as demonstrated by fluorescent viability assays and secretion of albumin for the one-week culture period.
Asunto(s)
Reactores Biológicos , Técnicas de Cultivo de Célula/instrumentación , Hepatocitos/citología , Técnicas Analíticas Microfluídicas/instrumentación , Supervivencia Celular , Hepatocitos/fisiología , HumanosRESUMEN
We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue-like culture and high-throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 microm wide cell culture pocket, an artificial endothelial barrier with 2 microm pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over 1 week in a solid tumor-like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for "flow cell" based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow-through biochemistry. Each fluidically independent tissue unit contained approximately 500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti-cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384-well dish for up to 5 days of continuous drug exposure.
Asunto(s)
Técnicas Analíticas Microfluídicas , Antineoplásicos/farmacología , Bioquímica/métodos , Biotecnología/métodos , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Separación Celular , Relación Dosis-Respuesta a Droga , Diseño de Equipo , Células HeLa , Humanos , Microfluídica , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Factores de TiempoRESUMEN
Primary hepatocytes represent a physiologically relevant model for drug toxicity screening. Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver acinus. This unit consisted of a cord of hepatocytes (50 x 30 x 500 microm) fed by diffusion of nutrients across the microfluidic endothelial-like barrier from a convective transport vessel (10 nL/min). This configuration sustained rat and human hepatocytes for 7 days without an extracellular matrix (ECM) coating. Experiments with the metabolism mediated liver toxicant diclofenac showed no hepatotoxicity after 4 h and an IC(50) of 334 +/- 41 microM after 24 h.
Asunto(s)
Biomimética/instrumentación , Células Endoteliales/fisiología , Hepatocitos/citología , Hepatocitos/fisiología , Hígado Artificial , Técnicas Analíticas Microfluídicas/instrumentación , Ingeniería de Tejidos/instrumentación , Animales , Biomimética/métodos , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Células Cultivadas , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Circulación Hepática/fisiología , Técnicas Analíticas Microfluídicas/métodos , Ratas , Ingeniería de Tejidos/métodosRESUMEN
BACKGROUND: Phenylketonuria (PKU) is associated with dopaminergic depletion in the dorsolateral prefrontal cortex and abnormalities of myelination. Both mechanisms may lead to deficits in cognitive functioning. Studies of cognitive outcome in children treated with PKU at an early stage have suggested that there are benefits in remaining on diet into adolescence. AIM: To assess the nature and extent of any cognitive deficits in adults treated at an early stage with PKU who had discontinued their diets in adolescence. METHOD: 25 patients (aged 18-38 years) who were diagnosed early and had discontinued their diets in adolescence were compared with 25 adults (aged 18-38 years) with PKU on continuous diet, and with a healthy control group (n = 45). RESULTS: The groups differed significantly on accuracy (p = 0.007) and speed (p = 0.001) of performance on an n-back working memory task and on speed of performance (p = 0.001) on a flanker inhibitory task, but not on flanker accuracy, object alternation learning or perceptual judgement tasks (all p>0.05). The off-diet group performed significantly below the on-diet group on n-back accuracy (p = 0.007) and flanker speed (p = 0.05), and significantly below the control group on n-back speed (p = 0.002) and flanker speed (p = 0.001). CONCLUSION: The findings suggest that although discontinuing diet in adolescence appears disadvantageous compared with remaining on continuous diet, any deficits are relatively subtle.