An efficient synthetic route to 1,3-bis(arylethynyl)isobenzofuran using alkoxybenzocyclobutenone as a reactive platform.

An efficient synthetic method of 1,3-bis(arylethynyl)isobenzofurans is developed. Nucleophilic addition of alkynyllithium to benzocyclobutenone and subsequent oxidative ring cleavage of the four-membered ring gave a keto-aldehyde, which, in turn, accepted the second nucleophile to produce isobenzofurans after acid treatment.

Lower intracuff pressure of laryngeal mask airway in the lateral and prone positions compared with that in the supine position.

We compared the intracuff pressure (ICP) of a laryngeal mask airway (LMA) in the lateral and prone positions with that in the supine position. One hundred and eight patients, weighing 50-70 kg, scheduled for elective orthopedic and plastic surgery, were assigned to three groups, based on their body position during surgery. General anesthesia was induced and then a size 4 deflated LMA was inserted in each patient in the supine (group 1; n = 42), lateral (group 2; n = 45), or prone position (group 3; n = 21). The LMA cuff was inflated with 15 ml of air. Anesthesia was maintained without nitrous oxide, and the ICP was measured until LMA removal in the supine position. ICP in groups 2 and 3 was significantly lower than that in group 1 from immediately after insertion to the end of surgery. After surgery, turning from the lateral (group 2) or prone (group 3) position to the supine position significantly raised the ICP. Because the ICP is related to the seal pressure of the LMA and postoperative pharyngolaryngeal morbidity, we recommend evaluating and adjusting the ICP appropriately in each body position.

Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats.

BACKGROUND: Acute inflammatory reactions cause neuronal damage in cerebral ischemia-reperfusion. Urinary trypsin inhibitor (UTI), a serine protease inhibitor, is cytoprotective against ischemia-reperfusion injury in the liver, intestine, kidney, heart, and lung through its antiinflammatory activity. Neuroprotective action of UTI on transient global cerebral ischemia has been documented. This is the first study to determine whether UTI is neuroprotective against transient focal cerebral ischemia. METHODS: Adult male Wistar rats were randomly assigned to the following treatment groups: 0.9% saline (control, n = 9); 100,000 U/kg UTI (n = 9); and 300,000 U/kg UTI (n = 9). Treatments were performed intravenously 10 min before right middle cerebral artery occlusion for 2 h and subsequent reperfusion. Ninety-six hours after the onset of reperfusion, the motor neurologic deficit and the cerebral infarct size were evaluated. Furthermore, immunohistochemical staining for myeloperoxidase and nitrotyrosine to count infiltrating neutrophils and nitrated cells, respectively, was performed on the brain sections. RESULTS: Infarct volume in the 300,000 U/kg UTI group was smaller than in the 100,000 U/kg UTI and saline control groups (P < 0.05). Treatment with 300,000 U/kg UTI showed a trend to improve neurologic outcome but did not reach statistical significance (P = 0.0693). The significant decrease in neutrophil infiltration was observed in the ischemic hemisphere treated with 300,000 U/kg UTI compared with saline control (P < 0.05). Nitrotyrosine deposition in the ischemic hemisphere was significantly reduced in the 300,000 U/kg UTI group compared with saline control and 100,000 U/kg UTI groups (P < 0.05). CONCLUSIONS: Intravenous pretreatment with 300,000 U/kg UTI reduces focal ischemia-reperfusion injury in the rat brain, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.

Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia.

BACKGROUND: Excessive extracellular glutamate produced by cerebral ischemia has been proposed to initiate the cascade toward neuronal cell death. Changes in extracellular glutamate concentration are closely linked to changes in intracellular calcium ion concentration. Dantrolene inhibits calcium release from intracellular calcium stores. In this study, the authors investigated the effects of dantrolene on extracellular glutamate accumulation and neuronal degeneration in a rat model of transient global forebrain ischemia. METHODS: Male Wistar rats weighing 230-290 g were anesthetized with halothane in nitrous oxide-oxygen and were subjected to 10 min of transient forebrain ischemia using a four-vessel occlusion technique. Fifteen minutes before ischemic injury, dantrolene sodium (5 mm), dimethyl sulfoxide as a vehicle for dantrolene, or artificial cerebrospinal fluid as a control was intracerebroventricularly administered (n = 8 in each group). In the hippocampal CA1 subfield, the extracellular glutamate concentration in vivo was measured during the periischemic period with a microdialysis biosensor, and the number of intact neurons was evaluated on day 7 after reperfusion. RESULTS: Both dantrolene and dimethyl sulfoxide significantly reduced the ischemia-induced increase in glutamate concentration to a similar extent, i.e., by 53 and 51%, respectively, compared with artificial cerebrospinal fluid (P < 0.01). The number of intact hippocampal CA1 neurons (mean +/- SD; cells/mm) in dantrolene-treated rats (78 +/- 21) was significantly higher than that in artificial cerebrospinal fluid- (35 +/- 14; P < 0.001) and dimethyl sulfoxide-treated (56 +/- 11; P < 0.05) animals. Dimethyl sulfoxide also significantly increased the number of preserved neurons in comparison with artificial cerebrospinal fluid (P < 0.05). CONCLUSIONS: Intracerebroventricular dantrolene prevents delayed neuronal loss in the rat hippocampal CA1 region subjected to transient ischemia; however, this neuroprotection cannot be accounted for only by the reduced concentrations of extracellular glutamate during ischemia.