RESUMEN
The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.
Asunto(s)
Ansiedad/sangre , Ansiedad/líquido cefalorraquídeo , Oxitocina/sangre , Oxitocina/líquido cefalorraquídeo , Adolescente , Adulto , Ansiedad/psicología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Estadística como Asunto , Adulto JovenRESUMEN
Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n = 3, 7.5 years, 20.0 pg/ml, 0.16 cm(2); grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm(2); grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm(2); grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm(2); grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm(2). Results suggest that horses with pituitary histologic grade > or =3 respond to domperidone with increased plasma ACTH concentration.
Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Domperidona , Enfermedades de los Caballos/diagnóstico , Enfermedades de la Hipófisis/veterinaria , Adenohipófisis Porción Intermedia/patología , Animales , Antagonistas de Dopamina , Femenino , Enfermedades de los Caballos/metabolismo , Caballos , Masculino , Tamaño de los Órganos , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/metabolismo , Adenohipófisis Porción Intermedia/metabolismoRESUMEN
Centrifugal elutriation was used to produce cell cycle enrichedfractions of four commercially relevant recombinant cell lines,chosen to allow for variation in properties due to construct,expression system and parent cell type, from normally growingheterogeneous batch cultures. As these fractions had identicalculture histories and had not been subjected to any insult orstress which was likely to have adversely affected cellularmetabolism, they were ideal for further study of cellularproperties. Specific productivity, cell size and cell cyclestate of replicate elutriated fractions were measured for eachcell line. Results showed that cell size was the major cellulardeterminant of productivity for all cell lines examined. Productformation was not restricted to any particular cell cycle phaseand in all cases, production occurred irrespective of cell cyclephase. Specific productivity was lowest when the majority ofcells in the fraction were G(1), intermediate when themajority of cells in the fraction were S phase and greater whenthe majority of cells in the fraction were in G(2)/M. However, the evidence suggests that size is the major cellulardeterminant of productivity; the apparent relationship betweencell cycle and productivity is secondary and can simply beascribed to the increasing size of cells as they progress thoughthe cell cycle. Thus, in addition to cell density and viabilitycell size is the cellular parameter which should be incorporatednot only into mathematical models of recombinant mammalian cellproduction processes but also into process monitoring andcontrol strategies.
RESUMEN
BACKGROUND: Operating room fires fueled by surgical drapes and ignited by high-energy surgical tools in air and oxygen-enriched atmospheres continue to occur. METHODS: The authors examined the time to ignition of huck towels and three commonly used surgical drape materials in air, 50% oxygen, and 95% oxygen using a carbon dioxide surgical laser as an ignition source. In addition, a phenol-polymer fabric was tested. RESULTS: In air, polypropylene and phenol polymer do not ignite. For polypropylene, the laser instantly vaporized a hole, and therefore, interaction between the laser and material ceased. When tested in combination with another material, the polypropylene time to ignition assumed the behavior of the material with which it was combined. For phenol polymer, the laser did not penetrate the material. Huck towels, cotton-polyester, and non-woven cellulose-polyester ignited in air with decreasing times to ignition. All tested materials ignited in 50% and 95% oxygen. CONCLUSION: The results of this study reveal that with increasing oxygen concentration, the time to ignition becomes shorter, and the consequences become more severe. The possibility exists for manufacturers to develop drape materials that are safer than existing materials.