thiourea and Sleep-Apnea-Syndromes

Obstructive sleep apnea is associated with neural injury and dysfunction. Hypoxia/reoxygenation exposures, modeling sleep apnea, injure select populations of neurons, including hypoglossal motoneurons. The mechanisms underlying this motoneuron injury are not understood. We hypothesize that endoplasmic reticulum injury contributes to motoneuron demise. Hypoxia/reoxygenation exposures across 8 weeks in adult mice upregulated the unfolded protein response as evidenced by increased phosphorylation of PERK [PKR-like endoplasmic reticulum (ER) kinase] in facial and hypoglossal motoneurons and persistent upregulation of CCAAT/enhancer-binding protein-homologous protein (CHOP)/growth arrest and DNA damage-inducible protein (GADD153) with nuclear translocation. Long-term hypoxia/reoxygenation also resulted in cleavage and nuclear translocation of caspase-7 and caspase-3 in hypoglossal and facial motoneurons. In contrast, occulomotor and trigeminal motoneurons showed persistent phosphorylation of eIF-2a across hypoxia/reoxygenation, without activations of CHOP/GADD153 or either caspase. Ultrastructural analysis of rough ER in hypoglossal motoneurons revealed hypoxia/reoxygenation-induced luminal swelling and ribosomal detachment. Protection of eIF-2alpha phosphorylation with systemically administered salubrinal throughout hypoxia/reoxygenation exposure prevented CHOP/GADD153 activation in susceptible motoneurons. Collectively, this work provides evidence that long-term exposure to hypoxia/reoxygenation events, modeling sleep apnea, results in significant endoplasmic reticulum injury in select upper airway motoneurons. Augmentation of eIF-2a phosphorylation minimizes motoneuronal injury in this model. It is anticipated that obstructive sleep apnea results in endoplasmic reticulum injury involving motoneurons, whereas a critical balance of phosphorylated eIF-2a should minimize motoneuronal injury in obstructive sleep apnea.

Topics: Animals; Brain Stem; Caspases; Choline O-Acetyltransferase; Cinnamates; Disease Models, Animal; eIF-2 Kinase; Endoplasmic Reticulum; Eukaryotic Initiation Factor-2; Gene Expression Regulation; Hypoxia; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Motor Neurons; Oxidative Stress; Phosphorylation; Sleep Apnea Syndromes; Thiourea; Transcription Factor CHOP

Allergic contact dermatitis of the scalp is relatively uncommon. This is a case report of a patient with chronic scalp dermatitis in the distribution of his continuous positive airway pressure (CPAP) mask neoprene rubber strap. Our objective was to identify any relevant contact allergens. Patch testing to the North American Contact Dermatitis Group (NACDG) Standard Allergens, a series of supplemental rubber allergens, and a sample of the neoprene from the patient's mask strap was performed. Relevant allergies to dialkyl thioureas, and the neoprene rubber portion of the CPAP mask strap were identified. Replacement with a cloth strap resulted in clearing of the dermatitis.

Topics: Dermatitis, Allergic Contact; Humans; Irritants; Male; Masks; Middle Aged; Neoprene; Oxygen Inhalation Therapy; Patch Tests; Scalp Dermatoses; Sleep Apnea Syndromes; Thiourea

Topics: Dermatitis, Allergic Contact; Equipment and Supplies; Female; Hair Diseases; Humans; Middle Aged; Patch Tests; Skin; Sleep Apnea Syndromes; Thiourea

We investigated the neural and chemical mechanisms contributing to the immediate ventilatory responses to laryngeal exposure to wood smoke in anesthetized Sprague-Dawley rats. Five milliliters of wood smoke were delivered into a functionally isolated larynx at a constant flow rate of 1.4 ml/s while the animals breathed spontaneously. Within 1 s after exposure, laryngeal wood smoke consistently triggered an apnea in each of the 42 rats tested. The apneic duration reached 1,636.4 +/- 105.4 (SE) % (n = 42) of the baseline expiratory duration. This apneic response was not affected by denervation of recurrent laryngeal nerves (n = 6) or by removal of smoke particulates (n = 14), but it was totally eliminated by topical application of an anesthetic (n = 8; lidocaine hydrochloride, 8%) to the laryngeal mucosa or by sectioning of the superior laryngeal nerves (n = 42). Furthermore, laryngeal application of a hydroxyl radical scavenger (dimethylthiourea; 500 mg/ml; n = 8) greatly diminished or abolished the smoke-induced apneic response, but it did not affect the apneic response evoked by laryngeal exposure to air saturated with 6% ammonia. These results suggest that the immediate apneic response to laryngeal wood smoke is a reflex resulting from the stimulation of the superior laryngeal afferents by the gas phase of wood smoke and that the stimulation is mediated through a hydroxyl radical mechanism.

Topics: Ammonia; Anesthesia; Animals; Free Radical Scavengers; Laryngeal Nerves; Larynx; Male; Rats; Rats, Sprague-Dawley; Recurrent Laryngeal Nerve; Reflex; Sleep Apnea Syndromes; Smoke; Smoke Inhalation Injury; Thiourea; Wood