RESUMEN
Avian brood parasitism is an evolutionarily derived behavior for which the neurobiological mechanisms are mostly unexplored. We aimed to identify brain regions that have diverged in the brood-parasitic brain using relative transcript abundance of social neuropeptides and receptors. We compared behavioral responses and transcript abundance in three brain regions in the brown-headed cowbird (BHCO), a brood parasite, and a closely related parental species, the red-winged blackbird (RWBL). Females of both species were treated with mesotocin (MT; avian homolog of oxytocin) or saline prior to exposure to nest stimuli. Results reveal that MT promotes approach toward nests with eggs rather than nests with begging nestlings in both species. We also examined relative transcript abundance of the five social neuropeptides and receptors in the brain regions examined: preoptic area (POA), paraventricular nucleus (PVN) and bed nucleus of the stria terminalis (BST). We found that MT-treated cowbirds but not blackbirds exhibited lower transcript abundance for two receptors, corticotropin-releasing factor 2 (CRFR2) and prolactin receptor (PRLR) in BST. Additionally, MT-treated cowbirds had higher PRLR in POA, comparable to those found in blackbirds, regardless of treatment. No other transcripts of interest exhibited significant differences as a result of MT treatment, but we found a significant effect of species in the three regions. Together, these results indicate that POA, PVN, and BST represent neural nodes that have diverged in avian brood parasites and may serve as neural substrates of brood-parasitic behavior.
Asunto(s)
Comportamiento de Nidificación , Oxitocina , Animales , Oxitocina/metabolismo , Oxitocina/genética , Oxitocina/farmacología , Oxitocina/análogos & derivados , Femenino , Pájaros Cantores/genética , Encéfalo/metabolismo , Especificidad de la Especie , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleos Septales/metabolismo , Área Preóptica/metabolismoRESUMEN
Background: The pathogenesis of Graves' hyperthyroidism (GH) and associated Graves' orbitopathy (GO) appears to involve stimulatory autoantibodies (thyrotropin receptor [TSHR]-stimulating antibodies [TSAbs]) that bind to and activate TSHRs on thyrocytes and orbital fibroblasts. In general, measurement of circulating TSHR antibodies by clinical assays correlates with the status of GH and GO. However, most clinical measurements of TSHR antibodies use competitive binding assays that do not distinguish between TSAbs and antibodies that bind to but do not activate TSHRs. Moreover, clinical assays for TSAbs measure stimulation of only one signaling pathway, the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, in engineered cells that are not thyrocytes or orbital fibroblasts. We determined whether measuring TSAbs by a cAMP-PKA readout in engineered cells accurately reveals the efficacies of stimulation by these antibodies on thyrocytes and orbital fibroblasts. Methods: We measured TSAb stimulation of normal human thyrocytes and orbital fibroblasts from patients with GO in primary cultures in vitro. In thyrocytes, we measured secretion of thyroglobulin (TG) and in orbital fibroblasts secretion of hyaluronan (hyaluronic acid [HA]). We also measured stimulation of cAMP production in engineered TSHR-expressing cells in an assay similar to clinical assays. Furthermore, we determined whether there were differences in stimulation of thyrocytes and orbital fibroblasts by TSAbs from patients with GH alone versus from patients with GO understanding that patients with GO have accompanying GH. Results: We found a positive correlation between TSAb stimulation of cAMP production in engineered cells and TG secretion by thyrocytes as well as HA secretion by orbital fibroblasts. However, TSAbs from GH patients stimulated thyrocytes more effectively than TSAbs from GO patients, whereas TSAbs from GO patients were more effective in activating orbital fibroblasts than TSAbs from GH patients. Conclusions: Clinical assays of stimulation by TSAbs measuring activation of the cAMP-PKA pathway do correlate with stimulation of thyrocytes and orbital fibroblasts; however, they do not distinguish between TSAbs from GH and GO patients. In vitro, TSAbs exhibit selectivity in activating TSHRs since TSAbs from GO patients were more effective in stimulating orbital fibroblasts and TSAbs from GH patients were more effective in stimulating thyrocytes.
Asunto(s)
Autoanticuerpos/inmunología , Fibroblastos/inmunología , Oftalmopatía de Graves/complicaciones , Células Epiteliales Tiroideas/inmunología , Adulto , Autoanticuerpos/análisis , Femenino , Fibroblastos/metabolismo , Enfermedad de Graves/sangre , Enfermedad de Graves/inmunología , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/patología , Humanos , Masculino , Persona de Mediana Edad , Células Epiteliales Tiroideas/metabolismo , Tirotropina/metabolismoAsunto(s)
Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Mixedema/tratamiento farmacológico , Rituximab/uso terapéutico , Enfermedad Aguda , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Enfermedad de Graves/complicaciones , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Mixedema/etiología , Rituximab/administración & dosificaciónRESUMEN
Six locally isolated strains of Penicillium were checked for their potential to produce cyclosporine A through submerged fermentation. The medium used for drug production was composed of glucose, 5%; peptone, 1%; KH2PO4, 0.5% and KCl, 0.25% (w/v). Butyl acetate was used to extract the fermentation medium for cyclosporine 'A' analysis. The confirmation analysis was done through high performance liquid chromatography and the chromatograms obtained were compared with that of Sandimmun Neoral (®)capsule (Novartis) containing 100 mg of cyclosporine and with the external standard cyclosporine A 98.5% pure. Only chromatogram of Penicillium fellutanum (FCBP 937) isolated from Guava fruit showed a peak at 2.768, which was comparable with both the standards. The amount of drug calculated was 16.18 µg/ml.