RESUMEN
This study tests the potential for using Armadillo officinalis as a bioindicator of exposure to and activation of benzene metabolic pathways using an in vivo model. A. officinalis specimens collected in a natural reserve were divided into a control and three test groups exposed to 2.00, 5.32 or 9.09 µg/m(3) benzene for 24h. Three independent tests were performed to assess model reproducibility. Animals were dissected to obtain three pooled tissue samples per group: hepatopancreas (HEP), other organs and tissues (OOT), and exoskeleton (EXO). Muconic acid (MA), S-phenylmercapturic acid (S-PMA), two human metabolites of benzene, and changes in mtDNA copy number, a human biomarker of benzene exposure, were determined in each sample; benzene was determined only in EXO. MA was measured by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection, S-PMA by triple quadrupole mass spectrometer liquid chromatography with electro spray ionization (LC-MS-ESI-TQD), mtDNA by real-time quantitative PCR and end-point PCR, and benzene by quadrupole mass spectrometer head-space gas chromatography (HSGC-MS). MA and S-PMA levels rose both in HEP and OOT; EXO exhibited increasing benzene concentrations; and mtDNA copy number rose in HEP but not in OOT samples. Overall, our findings demonstrate that A. officinalis is a sensitive bioindicator of air benzene exposure and show for the first time its ability to reproduce human metabolic dynamics.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Benceno/toxicidad , Isópodos/efectos de los fármacos , Acetilcisteína/análogos & derivados , Acetilcisteína/análisis , Acetilcisteína/metabolismo , Contaminantes Atmosféricos/farmacocinética , Animales , Benceno/farmacocinética , Biomarcadores/análisis , Cromatografía Líquida de Alta Presión/métodos , ADN Mitocondrial/análisis , Monitoreo del Ambiente , Cromatografía de Gases y Espectrometría de Masas , Hepatopáncreas/efectos de los fármacos , Hepatopáncreas/metabolismo , Humanos , Isópodos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Ácido Sórbico/análogos & derivados , Ácido Sórbico/análisis , Ácido Sórbico/metabolismo , Distribución TisularRESUMEN
Helper-dependent adenoviral (HD-Ad) vectors have great potential for gene therapy applications; however, their administration induces acute toxicity that impairs safe clinical applications. We previously observed that PEGylation of HD-Ad vectors strongly reduces the acute response in murine and primate models. To evaluate whether PEGylated HD-Ad vectors combine reduced toxicity with the correction of pathological phenotypes, we administered an HD-Ad vector expressing the human apolipoprotein A-I (hApoA-I) to low-density lipoprotein (LDL)-receptor-deficient mice (a model for familial hypercholesterolemia) fed a high-cholesterol diet. Mice were treated with high doses of HD-Ad-expressing apo A-I or its PEGylated version. Twelve weeks later, LDL levels were lower and high-density lipoprotein (HDL) levels higher in mice treated with either of the vectors than in untreated mice. After terminal killing, the areas of atherosclerotic plaques were much smaller in the vector-treated mice than in the control animals. Moreover, the increase in pro-inflammatory cytokines was lower and consequently the toxicity profile better in mice treated with PEGylated vector than in mice treated with the unmodified vector. This finding indicates that the reduction in toxicity resulting from PEGylation of HD-Ad vectors does not impair the correction of pathological phenotypes. It also supports the clinical potential of these vectors for the correction of genetic diseases.
Asunto(s)
Adenoviridae/genética , Apolipoproteína A-I/genética , Terapia Genética , Vectores Genéticos , Virus Helper/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Animales , HDL-Colesterol/sangre , HDL-Colesterol/metabolismo , LDL-Colesterol/sangre , LDL-Colesterol/metabolismo , Citocinas/genética , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Humanos , Hiperlipoproteinemia Tipo II/patología , Ratones , Ratones Endogámicos C57BL , Placa Aterosclerótica/patología , Placa Aterosclerótica/terapia , Polietilenglicoles , Receptores de LDL/deficiencia , Receptores de LDL/genéticaRESUMEN
The ability of a cellular construct to guide and promote tissue repair strongly relies on three components, namely, cell, scaffold and growth factors. We aimed to investigate the osteopromotive properties of cellular constructs composed of poly-epsilon-caprolactone (PCL) and rabbit bone marrow stromal cells (BMSCs), or BMSCs engineered to express bone morphogenetic protein 4 (BMP4). Highly porous biodegradable PCL scaffolds were obtained via phase inversion/salt leaching technique. BMSCs and transfected BMSCs were seeded within the scaffolds by using an alternate flow perfusion system and implanted into non-critical size defects in New Zealand rabbit femurs. In vivo biocompatibility, osteogenic and angiogenic effects induced by the presence of scaffolds were assessed by histology and histomorphometry of the femurs, retrieved 4 and 8 weeks after surgery. PCL without cells showed scarce bone formation at the scaffold-bone interface (29% bone/implant contact and 62% fibrous tissue/implant contact) and scarce PCL resorption (16%). Conversely, PCL seeded with autologous BMSCs stimulated new tissue formation into the macropores of the implant (20%) and neo-tissue vascularization. Finally, the BMP4-expressing BMSCs strongly favoured osteoinductivity of cellular constructs, as demonstrated by a more extensive bone/scaffold contact.
Asunto(s)
Materiales Biocompatibles/química , Células de la Médula Ósea/citología , Proteínas Morfogenéticas Óseas/metabolismo , Caproatos/química , Fémur/cirugía , Lactonas/química , Células del Estroma/citología , Animales , Materiales Biocompatibles/metabolismo , Células de la Médula Ósea/metabolismo , Proteína Morfogenética Ósea 4 , Proteínas Morfogenéticas Óseas/genética , Trasplante de Células/métodos , Fémur/crecimiento & desarrollo , Fémur/metabolismo , Vectores Genéticos/genética , Osteogénesis , Polímeros/química , Conejos , Células del Estroma/metabolismo , Células del Estroma/trasplante , Factores de Tiempo , Ingeniería de Tejidos/métodos , Transfección , Trasplante AutólogoRESUMEN
Trichoniscus alexandrae Caruso is a blind troglobiont isopod; males possess secretory and sensory organs on the cephalon and 1st pereionite consisting of cuticular pits hosting a tuft of setae and gland openings. Such organs are absent in females. Three types of cuticular structures have been observed: (a) lamellar setae, which likely play a role in protecting the gland openings and favouring the evaporation of secretions; (b) contact chemoreceptors, each provided with six bipolar sensory cells, a scolopale cell and enveloping cells; (c) a secretory cell complex, consisting of a long cylindrical slender duct-forming cell, with the function of transporting to the cuticular surface a secretion produced by two deeper secretory cells. The duct-forming cell is characterized by the presence of numerous microtubules in its cytoplasm, and is provided with a flattened duct. It is suggested that the secretion produced by the secretory cells could serve for sex-recognition.
Asunto(s)
Crustáceos/ultraestructura , Isópodos/ultraestructura , Órganos de los Sentidos/ultraestructura , Animales , Crustáceos/anatomía & histología , Femenino , Masculino , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Modelos BiológicosRESUMEN
Oculo-facio-cardio-dental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental and cardiac systems. The syndrome is an X-linked dominant trait and it might be lethal in males. This syndrome is usually caused by mutations in the BCL6 interacting co-repressor gene (BCOR). We described a female child with mild phenotype of oculo-facio-cardio-dental syndrome. Array-comparative genomic hybridization (a-CGH) analysis revealed a de novo heterozygous deletion in the Xp11.4 region of approximately 2.3 Mb, involving BCOR and ornithine carbamoyl-transferase (OTC) genes. The deletion observed was subsequently confirmed by real time PCR. In this study we report a first case with co-occurrence of BCOR and OTC genes completely deleted in OFCD syndrome.
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Anomalías Múltiples/diagnóstico , Catarata/congénito , Defectos de los Tabiques Cardíacos/diagnóstico , Microftalmía/diagnóstico , Ornitina Carbamoiltransferasa/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Anomalías Múltiples/genética , Catarata/diagnóstico , Catarata/genética , Preescolar , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , Femenino , Defectos de los Tabiques Cardíacos/genética , Humanos , Microftalmía/genética , Eliminación de SecuenciaRESUMEN
Investigations indicate that the induction of long-term potentiation (LTP) may be mediated by postsynaptic N-methyl-D-aspartate (NMDA) receptors and that the maintenance of LTP may be initiated by nitric oxide (NO), a retrograde messenger carrying signals backward from the postsynaptic to the presynaptic neuron. The present study compared amnestic effects of dizocilpine maleate (MK-801), an NMDA receptor antagonist, and nitro-L-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine (L-NOARG), nitric oxide (NO) inhibitors, in goldfish, using active-avoidance conditioning as the learning paradigm. The results showed that MK-801 and NO inhibitors produced anterograde amnesia at doses that did not impair performance processes necessary for learning to occur. Furthermore, MK-801 did not produce retrograde amnesia, whereas L-NAME did, suggesting that MK-801 impaired learning whereas NO inhibitors impaired memory consolidation and possibly also learning.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Memoria/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Amnesia/inducido químicamente , Análisis de Varianza , Animales , Maleato de Dizocilpina/farmacología , Electrochoque , Carpa Dorada , Potenciación a Largo Plazo/fisiología , NG-Nitroarginina Metil Éster/farmacología , Nitroarginina/farmacología , Receptores de N-Metil-D-Aspartato/fisiología , Factores de TiempoRESUMEN
OBJECTIVE: To examine the characteristics of patients admitted to the Medical Intensive Care Unit (MICU) after intentional drug overdose. DESIGN: Retrospective chart review, descriptive. SETTING: Midwestern teaching hospital. SUBJECTS: Convenience sample of 43 patients admitted to the MICU after intentional drug overdose. OUTCOME MEASURES: Survival and disposition of those patients who survived and were discharged from the MICU. RESULTS: Ninety-five percent of the patients survived and were discharged from the MICU; Acute Physiology and Chronic Health Evaluation II scores ranged from 1 to 29 (mean, 8); Glascow Coma Scale scores ranged from 3 to 15 (mean 12.5); five patients were intubated and two patients had serious electrocardiograph changes requiring pharmacologic intervention for dysrhythmia. CONCLUSIONS: Neurologic findings were the best indicators of serious complications after drug overdose. THerefore, patients with a Glascow Coma Scale score of more than six, and who are not intubated, may not need admission to an intensive care unit.
Asunto(s)
Cuidados Críticos , Sobredosis de Droga/terapia , APACHE , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sobredosis de Droga/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Intento de Suicidio , Resultado del TratamientoRESUMEN
Hospital nurses led weekly group sessions to provide dermatologic inpatients a supportive climate in which to share common concerns about skin disease and a forum for dissemination of dermatologic information. Session leaders kept a journal, noting themes and group dynamic patterns for each meeting. Participants also responded to a session evaluation questionnaire. Data from the journal and questionnaires were collected for one year to describe the issues and concerns raised in a support group for dermatologic patients and to assess the effectiveness of this approach in overall patient management. Three themes were consistently discussed: problems with stress, self-esteem, and social interaction; concerns with medical treatment; and coping with loss. Participants indicated that support and encouragement had been given and received. Need for a dermatologic patient support group was demonstrated. Location of such a group in an outpatient day-care setting was recommended.
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Grupos de Autoayuda , Enfermedades de la Piel/psicología , Medio Social , Apoyo Social , Adaptación Psicológica , Humanos , Relaciones Interpersonales , Autoimagen , Estrés Psicológico , Encuestas y CuestionariosRESUMEN
A program was implemented by clinical nurse specialists to manage the costs of the confused, agitated, or suicidal hospitalized patient. Key strategies used to implement and maintain the program are presented along with clinical and cost outcomes.
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Confusión/enfermería , Enfermeras Clínicas , Personal de Enfermería en Hospital/economía , Enfermería Psiquiátrica , Agitación Psicomotora/enfermería , Intento de Suicidio/prevención & control , Control de Costos , Humanos , Enfermeras Clínicas/economía , Personal de Enfermería en Hospital/provisión & distribución , Evaluación de Resultado en la Atención de Salud , Admisión y Programación de Personal/economía , Enfermería Psiquiátrica/economía , Recursos HumanosAsunto(s)
Grupos de Autoayuda , Enfermedades de la Piel/psicología , Adaptación Psicológica , Adulto , Femenino , Humanos , Autoimagen , Apoyo Social , Estrés PsicológicoAsunto(s)
Directivas Anticipadas/legislación & jurisprudencia , Personal de Enfermería en Hospital , Participación del Paciente/legislación & jurisprudencia , Regulación Gubernamental , Hospitales Universitarios/organización & administración , Humanos , Capacitación en Servicio , Relaciones Enfermero-Paciente , Personal de Enfermería en Hospital/educación , Ohio , Proyectos Piloto , Estados UnidosAsunto(s)
Coagulación Sanguínea/genética , Factor VIII/genética , Eliminación de Gen , Duplicación de Gen , Hemofilia A/genética , Inversión de Secuencia , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Hemofilia A/sangre , Hemofilia A/diagnóstico , Humanos , Lactante , Intrones , Italia , Masculino , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
The archaeal Sulfolobus solfataricus elongation factor 1alpha (SsEF-1alpha) bound to GTP or to its analogue guanyl-5'-yl imido diphosphate [Gpp(NH)p] formed a ternary complex with either Escherichia coli Val-tRNAVal or Saccharomyces cerevisiae Phe-tRNAPhe as demonstrated by gel-shift and gel-filtration experiments. Evidence of such an interaction also came from the observation that SsEF-1alphaz.rad;Gpp(NH)p was able to display a protective effect against either the spontaneous deacylation or the digestion of aminoacyl-tRNA by RNase A. Protection against the deacylation of aminoacyl-tRNA allowed evaluatation of the affinity of SsEF-1alphaz. rad;Gpp(NH)p for both aminoacyl-tRNAs used. The K'd values of the ternary complex containing S. cerevisiae Phe-tRNAPhe or E. coli Val-tRNAVal were 0.3 microM and 4.4 microM, respectively. In both cases, the affinity of SsEF-1alphaz.rad;Gpp(NH)p for aminoacyl-tRNA was three orders of magnitude lower than that of the homologous eubacterial ternary complexes, but comparable with the affinity shown by the ternary complex involving eukaryal EF-1alpha [Negrutskii, B.S. & El'skaya, A.V. (1998) Prog. Nucleic Acids Res. 60, 47-77]. As already observed with eukaryal EF-1alpha, SsEF-1alpha in its GDP-bound form was also able to protect the ester bond of aminoacyl-tRNA, even though with a 10-fold lower efficiency compared with SsEF-1alphaz.rad;Gpp(NH)p. The overall results indicated that the archaeal elongation factor 1alpha shares several properties with eukaryal EF-1alpha but not with eubacterial EF-Tu.
Asunto(s)
Proteínas Arqueales/metabolismo , Guanosina Trifosfato/metabolismo , Factor 1 de Elongación Peptídica/metabolismo , ARN de Archaea/metabolismo , ARN Bacteriano/metabolismo , ARN de Hongos/metabolismo , Aminoacil-ARN de Transferencia/metabolismo , Escherichia coli/metabolismo , Evolución Molecular , Guanosina Difosfato/metabolismo , Sustancias Macromoleculares , Ribonucleasa Pancreática/metabolismo , Saccharomyces cerevisiae/metabolismo , Especificidad de la Especie , Sulfolobus/metabolismoRESUMEN
The Wechsler Adult Intelligence Scale (WAIS) was administered to two groups of patients in the Santa Clara County Methadone Maintenance Program who were receiving low and moderate daily stabilized dosages of methadone hydrochloride. In the two separate statistical analyses performed, there were no significant differences found between subtest scores or verbal, performance, and full-scale scores of the groups measured. These results, combined with observations regarding the similarities of WAIS profiles of the two groups, indicate that cognitive functioning as measured by the WAIS was not differentially affected by the two dosages.
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Cognición/efectos de los fármacos , Metadona/farmacología , Administración Oral , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Dependencia de Heroína/rehabilitación , Humanos , Inteligencia/efectos de los fármacos , Metadona/uso terapéutico , Persona de Mediana Edad , Conducta Verbal , Escalas de WechslerRESUMEN
The process of methylation of chromosomal proteins [histones and nonhistone proteins (NHP)] in neuronal and glial cell nuclei obtained from cerebral hemispheres of rats at 1, 10, and 30 days of age was investigated. Purified neuronal and glial nuclei were incubated in the presence of S-adenosyl[methyl-3H]methionine. Histone and NHPs were extracted and fractionated by polyacrylamide gel electrophoresis. The results obtained indicate remarkable differences in the process of methylation of histones and NHPs between neuronal and glial nuclei, especially during the first period of postnatal development. In both nuclear populations the histone fraction H3 was labeled to a greater degree than the other fractions and showed the major changes during postnatal development. The densitometric and radioactive patterns of NHPs show considerable changes in the two nuclear populations at the various ages examined. The main difference between neuronal and glial nuclei consists in the intense methylation of proteins with a molecular weight of approximately 100,000, which are present in neuronal nuclei and virtually absent in glial ones. The results obtained may be correlated with the different chromatin structures of neuronal and glial nuclei and with the patterns of maturation and differentiation of neuronal and glial cells during postnatal development.
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Encéfalo/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Histonas/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Técnicas In Vitro , Metilación , Ratas , Ratas Endogámicas , TritioRESUMEN
RNA synthesis in rat cerebral hemispheres at 1, 5, and 10 days of age and the relative contribution brought by neuronal and glial nuclei to RNA synthesis was investigated. The experiments were carried out both in vivo (by i.p. injection of [3H]uridine) and in vitro (either by incubation of tissue slices with [3H]uridine or by determination of RNA polymerase activities). The labeling of RNA decreases from 1 to 10 days of age both in vivo and in vitro; the decrease is of the same extent in neuronal and glial nuclei. RNA polymerase activity Mg2+-dependent does not change significantly from 1 to 10 days of age either in total, in neuronal, or in glial nuclei, whereas the Mn2+-dependent activity increases significantly over the same developmental period studied. The significance of RNA polymerase assay as an index of in vivo RNA synthesis is discussed.
Asunto(s)
Animales Recién Nacidos/metabolismo , Encéfalo/crecimiento & desarrollo , Neuroglía/metabolismo , Neuronas/metabolismo , ARN/biosíntesis , Animales , Encéfalo/metabolismo , Núcleo Celular/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , Magnesio/farmacología , Manganeso/farmacología , Neuroglía/ultraestructura , Neuronas/ultraestructura , Ratas , Ratas Endogámicas , Uridina/metabolismoRESUMEN
The effect of hypothyroidism on the vitro incorporation of [3H]uridine into different RNA species in tissue slices of rat cerebral hemispheres at 5, 10, 15, and 21 days of age has been investigated. Gel electrophoresis analysis of total, nuclear and microsomal RNA was also accomplished. The results obtained indicate that RNA labeling is differently influenced by hypothyroidism at the various ages examined. RNA labeling is not significantly affected at 5 days of age while at later ages and especially at 21 days it is higher in hypothyroid rats compared to the controls. Moreover distinct differences at the various ages in the transport of newly synthesized RNA from the nucleus to the cytoplasm in the two groups of animals were found. These results are in agreement with the hypothesis that thyroid hormone deficiency causes a delay of the processes of cell proliferation and differentiation in developing rat brain.
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Encéfalo/metabolismo , Hipotiroidismo/metabolismo , ARN/metabolismo , Uridina/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Microsomas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Acetylation, phosphorylation and methylation of nuclear proteins in rat cerebellum at 10 and 30 days of age were investigated in vitro. Isolated nuclei were incubated in the presence of [1-14C]acetyl CoA, S-adenosyl [methyl-3H]methionine and [gamma-32P]ATP and then separated into histones and non histone proteins (NHP), which were further fractionated by polyacrylamide gel electrophoresis. The results obtained indicate that acetylation, phosphorylation and methylation of both basic and acidic proteins decrease from 10 to 30 days of age. Electrophoretic analysis of histones shows that the decrease mainly concerns H1, H3, and H2b fractions. The H3 fraction is always more labeled than the other fractions and shows the major changes during postnatal development. Phosphorylation of H2a and H4 fractions increases from 10 to 30 days of age, whereas acetylation and methylation of these fractions do not show significant changes from 10 to 30 days. The densitometric and radioactive patterns of NHP show considerable changes between 10 and 30 days, especially in the high molecular weight region. The incorporation of 14C-acetyl and 3H-methyl groups and of 32P phosphate appears to be generalized throughout the molecular weight range and decreases from 10 to 30 days of age. The methylation of an as yet unidentified protein with a molecular weight of approximately 110,000 daltons occurred at both ages.
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Cerebelo/crecimiento & desarrollo , Proteínas Cromosómicas no Histona/metabolismo , Histonas/metabolismo , Procesamiento Proteico-Postraduccional , Acetilación , Animales , Cerebelo/metabolismo , Metilación , Fosforilación , Ratas , Ratas EndogámicasRESUMEN
DNA synthesis in nuclei and mitochondria purified from serum-supplemented rat glial cell cultures at different days after plating was studied. Furthermore in mitochondria, some enzymatic activities related to energy transduction (citrate synthase, malate dehydrogenase, total NADH-cytochrome c reductase, cytochrome oxidase and glutamate dehydrogenase) were measured. For DNA labeling [methyl-3H]thymidine was added to the culture medium at different days after plating. During the culture times studied the specific activity of total, nuclear, and mitochondrial DNA decreased from 8 days in vitro (DIV) to 21 DIV and increased at 30 DIV. The specific activity of nuclear DNA was always higher than that of mitochondrial DNA. The specific activity of the above mentioned mitochondrial enzymes increased from 8 DIV up to 21 DIV and decreased at 30 DIV, suggesting a relationship between the energy metabolism and the differentiation of glial cells in culture.
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Núcleo Celular/metabolismo , Replicación del ADN , ADN Mitocondrial/metabolismo , Metabolismo Energético , Neuroglía/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/citología , Mitocondrias/enzimología , Ratas , Timidina , Factores de TiempoRESUMEN
The purpose of this research was to identify the relationship between attending an ICU family support group and the family's appraisal of stress, social support, and hope. In addition, the family members' perceived benefits of attending an ICU family support family support group session does not significantly change stress levels, feelings of hope, and social support. Analysis of data reconfirms that family members of critically ill patients have a tremendous need for information. Although findings revealed that the majority of the family members who attended the support session would recommend attending again, it is unclear whether the support session method is the most beneficial and cost-effective means to support families of critically ill patients.