Influence of acoustic stress by noise on gastrointestinal motility in dogs

The effects of acoustic stress (AS) on gastrointestinal motility and their prevention by previous treatment with naloxone, phentolamine, propranolol, muscimol, and diazepam were investigated in intact and vagotomized fasted dogs fitted with chronically implanted strain gauges on the antrum at 10 cm from pylorus and on the jejunum at 70 and 140 cm from the pylorus. These effects were compared to those produced by intracerebroventricular administration of ovine corticotropin releasing factor (oCRF). Beginning 40–50 min after the occurrence of a gastric migrating motor complex (MMC), a 1-hr hearing of prerecorded intense music through earpieces (<100 dB) delayed the occurrence of the next gastric MMC observed after 2.8±1.2 hr, while jejunal MMC were still present at a normal frequency. During AS, heart rate and plasma cortisol were significantly increased by 32.7 and 215%, respectively, 10–15 min after the beginning of hearing. The AS-induced lengthening of the gastric MMC cycle as well as cortisol increase were abolished after previous administration of diazepam (0.5 mg/kg intramuscular) or muscimol (10 g/kg intravenous), while they were still present after naloxone (0.1 mg/kg intravenous), phentolamine (0.2 mg/kg intravenous), or propranolol (0.1 mg/kg intravenous). CRF administered intracerebroventricularly (100 ng/kg) also delayed the occurrence of gastric MMC without affecting jejunal motility, and this effect was not antagonized by previous treatment with diazepam or muscimol. Both the effects of AS and CRF were abolished after bilateral thoracic vagotomy. These results suggest that the selective inhibition of gastric motility induced by noise in dog is due to the CNS release of CRF which affects, in turn, the vagal output to the stomach. The suppressive action of diazepam or GABA agonist on noise-induced gastric hypomotility may be related to blockade of the AS-induced CRF release.     

Diamond-Blackfan anemia: promotion of marrow erythropoiesis in vitro by recombinant interleukin-3

To clarify the defective erythropoiesis in eight patients with Diamond- Blackfan anemia, we studied their bone marrow response in vitro to recombinant human interleukin-3 (IL-3) and recombinant granulocyte- macrophage colony-stimulating factor (GM-CSF). In an erythropoietin- containing assay system, specimens from six of the eight patients yielded low numbers of erythroid colonies compared to control values, and in five of these no erythropoietin dose-response could be elicited. Addition of IL-3, GM-CSF or both to cultures from the six patients had no effect on CFU-E-derived colonies. In contrast, IL-3 but not GM-CSF induced a marked increase in the number (183%) and size of the BFU-E- derived colonies in five of the six cases and partially corrected the impaired dose-response to erythropoietin in four. Bone marrow from the other two patients yielded numbers of CFU-E and BFU-E colonies comparable to controls and manifested similar increments in colonies with increasing concentrations of erythropoietin. When IL-3 was added to these cultures, further increments were observed in the number and size of BFU-E colonies. We conclude that IL-3 enhanced the marrow erythropoiesis in most of the patients and exerted a corrective effect on the aberrant colony formation in the presence of erythropoietin. The data raise the possibility of IL-3 as a therapeutic agent in Diamond- Blackfan anemia.