Melatonin enhances the hypoxic response of rat carotid body chemoreceptor

Melatonin attenuates carotid chemoreceptor response to hypercapnic acidosis and may contribute to the effect of circadian rhythms on the chemoreflex. The purpose of this study was to test the hypothesis that melatonin modulates rat carotid chemoreceptor response to hypoxia. To examine the effect of melatonin on the hypoxic response of the chemosensitive cells, cytosolic calcium ([Ca 2+]i) was measured by spectrofluorometry in fura-2-loaded type-I (glomus) cells dissociated from rat carotid bodies. Melatonin (0.01-10 nM) did not change the resting [Ca2+]i level of the glomus cells but it concentration-dependently increased peak [Ca2+] i response to cyanide or deoxygenated buffer. An agonist of melatonin receptors, iodomelatonin also enhanced the [Ca2+]i response to hypoxia. The melatonin-induced enhancement of the [Ca 2+]i response was abolished by pretreatment with nonselective mt1/MT2 antagonist, luzindole, and by MT 2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. These findings suggest that melatonin receptors in the glomus cells mediate the effect of melatonin on the chemoreceptor response to hypoxia. In addition, melatonin increased the carotid afferent response to hypoxia in unitary activities recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate-buffer saline. Furthermore, plethysmographic measurement of ventilatory activities in unanesthetized rats revealed that melatonin (1 mg/kg, i.p.) increased the ventilatory response to hypoxia. Hence, the circadian rhythm of melatonin in arterial blood can modulate the carotid chemoreceptor response to hypoxia. This modulation may be a physiological mechanism involved in the day-light differences in ventilatory activities. Copyright © Blackwell Munksgaard, 2004.link_to_subscribed_fulltex

Melatonin attenuates rat carotid chemoreceptor response to hypercapnic acidosis

Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on the chemoreceptor response to hypercapnic acidosis is mediated by melatonin receptors in the chemosensitive cells, cytosolic calcium ([Ca 2+]i) was measured by spectrofluorometry in fura-2-loaded glomus cells dissociated from rat carotid bodies. Melatonin (0.01-10 nM) per se did not change the [Ca2+]i levels of the glomus cells but it concentration-dependently attenuated the peak [Ca2+]i response to hypercapnic acidosis in the glomus cells. In addition, the [Ca 2+]i response was attenuated by 2-iodomelatonin, an agonist of melatonin receptors. The melatonin-induced attenuation of the [Ca2+]i response to hypercapnic acidosis was abolished by pretreatment with an non-selective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. In situ hybridization study with antisense mt1 and MT 2 receptor mRNA oligonucleotide probes showed an expression of mt1 and MT2 receptors in the rat carotid body. Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis in single- or pauci-fibers recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate-buffer saline. Results suggest that an activation of the melatonin receptors expressed in the glomus cells of the rat carotid body reduces the chemoreceptor response to hypercapnic acidosis. This modulation may play a physiological role in the influence of the circadian rhythms on the chemoreflex.link_to_subscribed_fulltex

An insight into processing and characteristics of magnesium based composites

Magnesium Technology423-42

Ambiguity in Requirements Engineering: Towards a Unifying Framework

A long stream of research in RE has been devoted to analyzing the occurrences and consequences of ambiguity in requirements documents. Ambiguity often occurs in documents, most often in natural language (NL) ones, but occasionally also in formal specifications, be it because of abstraction, or of imprecise designation of which real-world entities are denotated by certain expressions. In many of those studies, ambiguity has been considered a defect to be avoided. In this paper, we investigate the nature of ambiguity, and advocate that the simplistic view of ambiguity as merely a defect in the document does not do justice to the complexity of this phenomenon. We offer a more extensive analysis, based on the multiple linguistic sources of ambiguity, and present a list of real-world cases, both in written matter and in oral interviews, that we analyze based on our framework. We hope that a better understanding of the phenomenon can help in the analysis of practical experiences and in the design of more effective methods to detect, mark and handle ambiguity