RESUMEN
BACKGROUND: Acute Aspergillus fumigatus infection in immunocompetent patients is rare. This is the first known case of a patient who survived Aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ECMO) and antifungal therapy. CASE PRESENTATION: An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure. Owing to her severe clinical condition, she was treated for acute respiratory distress syndrome (ARDS) with veno-venous ECMO. Empiric antifungal therapy comprising voriconazole was also initiated owing to her history and a previous case report of aspergillosis after plant mulch exposure, though there was no microbiological proof at the time. A. fumigatus was later cultured and detected on antibody testing. The patient recovered, and ECMO was discontinued 1 week later. After 7 days of antifungal treatment, Aspergillus antibodies were undetectable. CONCLUSIONS: In cases of sepsis that occur after gardening, clinicians should consider Aspergillus inhalation as an aetiology, and early antimycotic therapy is recommended.
Asunto(s)
Aspergillus fumigatus/aislamiento & purificación , Jardinería , Aspergilosis Pulmonar/microbiología , Síndrome de Dificultad Respiratoria/etiología , Sepsis/microbiología , Antifúngicos/uso terapéutico , Oxigenación por Membrana Extracorpórea/métodos , Femenino , Humanos , Inmunocompetencia , Persona de Mediana Edad , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/terapia , Síndrome de Dificultad Respiratoria/terapia , Sepsis/complicaciones , Sepsis/terapiaRESUMEN
BACKGROUND: Feeding related peptides have been shown to be additionally involved in the central autonomic control of gastrointestinal functions. Recent studies have shown that ghrelin, a stomach-derived orexigenic peptide, is involved in the autonomic regulation of GI function besides feeding behavior. Pharmacological evidence indicates that ghrelin effects on food intake are mediated by neuropeptide Y in the central nervous system. METHODS: In the present study we examine the role of ghrelin in the central autonomic control of GI motility using intracerobroventricular and IP microinjections in a freely moving conscious rat model. Further the hypothesis that a functional relationship between NPY and ghrelin within the CNS exists was addressed. RESULTS: ICV injections of ghrelin (0.03 nmol, 0.3 nmol and 3.0 nmol/5 microl and saline controls) decreased the colonic transit time up to 43%. IP injections of ghrelin (0.3 nmol - 3.0 nmol kg(-1) BW and saline controls) decreased colonic transit time dose related. Central administration of the NPY1 receptor antagonist, BIBP-3226, prior to centrally or peripherally administration of ghrelin antagonized the ghrelin induced stimulation of colonic transit. On the contrary ICV-pretreatment with the NPY2 receptor antagonist, BIIE-0246, failed to modulate the ghrelin induced stimulation of colonic motility. CONCLUSION: The results suggest that ghrelin acts in the central nervous system to modulate gastrointestinal motor function utilizing NPY1 receptor dependent mechanisms.
Asunto(s)
Encéfalo/metabolismo , Colon/fisiología , Tránsito Gastrointestinal/fisiología , Hormonas Peptídicas/fisiología , Receptores Acoplados a Proteínas G/fisiología , Receptores de Neuropéptido/fisiología , Tercer Ventrículo/metabolismo , Animales , Arginina/administración & dosificación , Arginina/análogos & derivados , Arginina/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Ghrelina , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Masculino , Hormonas Peptídicas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores de Neuropéptido/antagonistas & inhibidores , Receptores de Neuropéptido Y/fisiologíaRESUMEN
Neuropeptide Y (NPY) neuronal projections from the arcuate nucleus (ARC) have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (PVN) as part of the ARC-PVN axis. The existence of a positive feedback loop involving CRF receptors in the PVN has been suggested. Exogenous NPY and CRF in the PVN have been shown to inhibit gastric acid secretion. Recently, we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via vagal pathways. To what extent NPY- and CRF-mediated mechanisms in the PVN contribute to the CNS modulation of gastric acid secretion is still an open question. In the present study, we performed consecutive bilateral microinjections of antagonists to NPY receptor subtypes Y1 and Y2 and to CRF1/2 receptors in the PVN and of the excitatory amino acid kainate in the ARC to assess the role of NPY- and CRF-mediated mechanisms in the kainate-induced effects on gastric acid secretion. Gastric acid secretion was measured at the basal condition and during pentagastrin (16 microg/kg body wt) stimulation. Microinjection of vehicle in the PVN and kainate in the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1 receptor antagonist BIBP-3226 (200 pmol) and the nonspecific CRF1/2 antagonist astressin (30 pmol) in the PVN abolished the inhibitory effect of neuronal activation in the ARC by kainate on gastric acid secretion. The CRF antagonist astressin was more effective. Pretreatment with the NPY-Y2 receptor antagonist BIIE-0246 (120 pmol) in the PVN had no significant effect. Our results indicate that activation of neurons in the ARC inhibits gastric acid secretion via CRF1/2 and NPY-Y1 receptor-mediated pathways in the PVN.