Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

Drug-induced bronchial asthma

In any case of acute bronchoconstriction the possibility of an adverse reaction to a drug should be considered. In many of such side reactions no allergic mechanism can be detected. Therefore, they are included into the category of pseudoallergic reactions (PAR). The clinically most important form of drug-induced bronchial asthma, analgesics asthma, belongs to this PAR group. A further risk for asthmatics are intravenous applications of contrast-media for roentgenography which in about 15% induce a severe, sometimes life-threatening pseudo-allergic adverse reaction. In asthmatics, the application of any beta-receptor blocking agents and also the use of parasympathicotonic eye drops for treatment of glaucoma are contraindicated. Paradoxical bronchial constriction following application of antiasthmatics are preponderantly caused by locally irritative actions, less frequently by genuine allergic phenomena or additive intolerance. The most reliable prophylaxis against drug-induced bronchial asthma consists in strong avoidance of all derivatives possibly capable to trigger any intolerance. A respective warning should entered into the emergency passport.     

Isolation impairs place preference conditioning to morphine but not aversive learning in mice

Morphine (8–100 mg/kg IP) induces place preference conditioning in mice. The effect of two different periods of isolation (15 and 30 days) was examined. Mice isolated for 15 days but not 30 days exhibited place preference conditioning to morphine (8 mg/kg). After 30 days of isolation morphine could not induce place preference conditioning with the following doses (8, 16, 64, 100 mg/kg). Social regrouping of male mice previously isolated for 30 days with naive female mice for 15 or 30 days resulted in a reappearance of the conditioned place preference to morphine (16 mg/kg). The specificity of this associative deficit was examined by testing learning in isolated compared to non-isolated mice in two distinct settings: escape learning in the Morris water maze and passive avoidance acquisition and retention. On the Morris water maze isolated mice did not differ from non-isolated mice regarding place learning, the probe trial or extinction. Isolated mice were unimpaired in passive avoidance acquisition and retention. It was concluded that the deficits in place preference conditioning were not the result of a global learning impairment in isolated mice. Received: 10 April 1996 /Final version: 20 September 1996     

Probable gas embolism during operative hysteroscopy caused by products of combustion

PURPOSE: Gas embolism is a rare but well documented entity during operative hysteroscopy, with an incidence of 10-50%. Catastrophic outcomes occur at a rate of three in 17,000 procedures. The purpose of this report is to present a non-fatal case of gas embolism probably caused by the gaseous products of combustion. CLINICAL FEATURES: A 50-yr-old woman with a history of menorrhagia was scheduled for hysteroscopy and endometrial ablation and polypectomy. Fifteen minutes into the procedure, with the patient in lithotomy position, 20 degree head down tilt, and breathing spontaneously, a sudden oxygen desaturation occurred from 97% to 87%. The patient's end-tidal carbon dioxide dropped from 46 mmHg to 27 mmHg. The patient's breathing pattern remained normal, respiratory rate remained 11-12 breaths x min(-1) but amplitude of the reservoir bag movement was increased. Cardiovascular variables remained stable. She responded rapidly to 100% oxygen and made an uneventful recovery. Having ruled out other possible causes, we concluded gas embolism was responsible for the fall in oxygen saturation and end-tidal CO(2). CONCLUSION: With all the precautions in place to minimize the likelihood of fluid overload and ambient air embolism occurring, we surmised that products of combustion were the cause of the gas embolism. During endometrial ablation, gaseous products of combustion, mainly carbon dioxide, accumulate. The gases may then contribute to the rise in uterine pressure that occurs as irrigation fluid enters the uterus and this rise in pressure in turn encourages passage of gas into the open venous sinuses.