Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels.

BACKGROUND: Intranasal noninhaled delivery of carbon dioxide (CO2) is efficacious in the symptomatic treatment of seasonal allergic rhinitis. The goal of this study was to determine whether and how 100% CO2 inhibits mast cell degranulation, thereby possibly contributing to the reduction of symptoms in seasonal allergic rhinitis. METHODS: Peritoneal mast cells isolated from rats and labelled with sulforhodamine-B (SFRM-B) were used to determine whether CO2 treatment could block mast cell degranulation and histamine release in response to 48/80. In addition, the effect of CO2 on intracellular calcium levels in unstimulated and stimulated mast cells was determined by fluorescent microscopy. RESULTS: Treatment with 48/80 caused >90% of mast cells containing SFRM-B to degranulate, resulting in a marked decrease in the fluorescent intensity within the mast cells, and simultaneously causing a significant increase in histamine release. Significantly, the stimulatory effect of 48/80 on fluorescent intensity and histamine levels was greatly inhibited (>95%) to near control levels by pretreatment with 100% CO2. Treatment with 48/80 also caused a robust transient increase in intracellular calcium, whereas pretreatment with CO2 repressed the increase in calcium (>70%) in response to 48/80. CONCLUSIONS: Results from this study provide the first evidence of a unique regulatory mechanism by which CO2 inhibits mast cell degranulation and histamine release by repressing stimulated increases in intracellular calcium. Thus, our data provide a plausible explanation for the reported therapeutic benefit of noninhaled intranasal delivery of 100% CO2 to treat allergic rhinitis.

Treatment of a Class II Division 1 malocclusion with a severe unilateral lingual crossbite with combined orthodontic/orthognathic surgery.

A 24-year-old woman had a Class II Division 1 malocclusion with a severe unilateral crossbite. The crossbite was due partially to the maxilla being much wider than the mandible, allowing the mandibular left canine and first and second premolars to overerupt, impinging on the palatal tissue in habitual occlusion. The maxillary left segment from the lateral incisor to the first molar also overerupted producing 2 planes of occlusion. The malocclusion was treated successfully with comprehensive orthodontics, combined with a 2 piece Lefort I osteotomy procedure, a 3 tooth mandibular segmental osteotomy procedure, and a bilateral sagittal split osteotomy procedure.

Large peripheral osteoma arising from the genial tubercle area.

In a review of the literature, it can be determined that large osteomas of the mandible are relatively rare. Of those that have been described, the location is normally posterior to the premolars on the lingual surface of the mandible or in the condylar area. This article presents a case of an atypical presentation of an osteoma arising from the genial tubercle area.

Alterations in maternal and fetal prostaglandin dehydrogenase as a result of maternal ethanol consumption.

Various lines of research have suggested that ethanol consumption may alter prostaglandin-related physiology. Our laboratory has reported that chronic exposure to high doses of ethanol lowers the ability of kidney and lung homogenates from rats to catabolize prostaglandin E2 and F2 alpha via 15-prostagladin dehydrogenase (PGDH). Because of the apparently unique role played by prostaglandins in conception, growth and development of the fetus and parturition, we have attempted to determine if the alterations observed in male rats also occur in females and if any alterations in fetal metabolism result from maternal ethanol exposure. Further, we have measured the influence of ethanol administration on renal clearance of the 15-keto metabolite of PGF2 alpha in an attempt to determine the in vivo significance of the enzyme inhibition observed in vitro. Initial results indicate the following. 1) Female Holtzman rats doses at 2.0, 5.0 and 7.0 mg ethanol/kg during the first, second, and third trimesters of pregnancy, respectively, showed losses in renal PGDH activity similar to those found in males (1.52 versus 1.05 picomole/min/mg, p < 0.001 by matched t-test). 2) Placental tissue (amnion) isolated from these same animals on day 21 of the pregnancies also showed a significant decrease in PGDH activity (14.79 versus 11.77 picomoles/min/mg, p < 0.01). 3) Kidney homogenates from fetuses delivered on day 21 of the pregnancies showed a significant increase in PGDH relative to pair-dosed controls (16.77 versus 12.65 picomoles/min/mg, p < 0.01). 4) In a separate experiment, urinary clearance of PGF2 alpha metabolite was inhibited in a dose related manner up to a level of 6 gm/kg.

The effect of ethanol on the metabolism of prostaglandins and related compounds.

Previous studies have shown that chronic consumption of ethanol by rats lowers the level of membrane-bound arachidonic acid (C20:4) and stimulates the in vitro measured rate of hepatic lipid peroxidation. These observations suggested that ethanol might thereby cause changes in the metabolic pathway leading to prostaglandins and related compounds. Initial studies demonstrated that chronic ethanol administration to male rats results in an impaired ability on the part of these animals to catabolize prostaglandins via renal prostaglandin dehydrogenase (PGDH) but no effect was observed on the synthesis of thromboxanes by blood platelets from these same animals. Experiments have now been carried out in an attempt to further assess the acute and chronic effects of ethanol on the metabolism of prostaglandins and prostacyclin. Generally, these results suggest a lack of an acute effect of ethanol and a dose dependency for the chronic effects.