4-(2-Hydroxy-benzyl-idene)-3-methyl-isoxazol-5(4H)-one.

The mol-ecular skeleton of the title mol-ecule, C(11)H(9)NO(3), is approximately planar (r.m.s. deviation = 0.0056 Å); the two rings form a dihedral angle of 6.5 (1)°. In the crystal structure, inter-molecular O-H⋯N hydrogen bonds involving the H atom of the hydr-oxy group and the N atom of the isoxazole ring link mol-ecules into chains running along the c axis.

(Z)-4-[4-(Dimethyl-amino)benzyl-idene]-3-methyl-isoxazol-5(4H)-one.

The title compound, C(13)H(14)N(2)O(2), an isoxazol-5-one derivative, was synthesized by a one-pot, three-component condensation reaction of methyl acetoacetate, hydroxy-lamine hydro-chloride and 4-(dimethyl-amino)benzaldehyde. All the non-H atoms are co-planar [r.m.s deviation = 0.0039 Å], with a Z configuration about the C=C bond. The dihedral angle between the phenyl ring and the isoxazole ring is 2.58 (19)°.

[Morphological observation of amifostine's protective effect on radiation induced early middle ear injury].

OBJECTIVE: To assess the radio-protective effect of amifostine on the middle ear in animal models by observing the morphological changes of middle ear mucosa. METHOD: Adult guinea pigs (n=38) were divided into the radiation group, the radiation-amifostine group and the control group. The first two groups were exposed to total 45 Gy of Gamma radiation which was administered to the right ear of each guinea pig with 3.0 Gy/fraction, 5 times per week, using a cobalt-60 machine. And the radiation+amifostine group was pretreated with the radio protector amifostine 100 mg/kg intra-peritoneally 30 min before each fraction of radiation. Sterile saline was administered intra-peritoneally in radiation group before ear irradiation. Two normal guinea pigs given no treatment were chosen as the control. The tympanic bullas were removed and the mucosae was processed for light microscope and scanning electron microscope examination on the 2nd and 30th days post irradiation to observe mucosa thickness, leukocyte and cilia. RESULT: Light microscope and scanning transmission electron microscope examination showed in radiation groups that the middle ear effusion occurred; the cilia and micro cilia fell off, fused or collapsed; their directions changed; the mucosa became thicker; and leukocytes were also found infiltrating into the mucosa. On the 30th day,the damage was more serious. As comparison, there was no manifest damage of the middle ear mucosa in radiation+amifostine group. The mucosa thickness and the leukocyte quantity of radiation group were obviously higher than that of radiation+amifostine group (P < 0.01). CONCLUSION: The middle ear mucosa was found to change over time after irradiation. Amifostine has a protective effect on radiation induced early middle ear injury.

The relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 expression.

PURPOSE: The objective of our study was to characterize the relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 (ICAM-1) expression in early-phase, radiation-induced otitis media and to illustrate the possible mechanism of early-phase radiation-induced otitis media. MATERIALS AND METHODS: A comparison study of middle ear tissue was performed by the expression of ICAM-1 and the electron microscope from total 38 guinea pigs. Group A, consisting of 2 pigs, was used as control, and these pigs were not irradiated. Groups B, C, D, and E, consisting of 9 pigs each, were irradiated. Sterile saline was administered intraperitoneally to the pigs in groups B and D before irradiation, and amifostine was administered intraperitoneally as an aqueous solution 30 minutes before irradiation to the pigs in groups C and E. The pigs in groups B and C were killed on the second day after irradiation, and the pigs in groups D and E were killed 30 days after irradiation. RESULTS: Intercellular adhesion molecule 1 was strongly expressed in the middle ear mucosa of the irradiated pigs after a 45-Gy dose of radiation was administered. Enhanced ICAM-1 expression was accompanied by pathomorphologic changes in the middle ear tissue. Scanning electron microscopy demonstrated the changes. Intercellular adhesion molecule 1 expression in the mucosa of the groups killed on the second day was stronger than that in the mucosa of the groups killed 30 days after irradiation. Amifostine protected the middle ear from radiation injury, and we found that the expression of ICAM-1 in the middle ear mucosa was down-regulated. However, slight expression of ICAM-1 remained 30 days after irradiation. CONCLUSIONS: Irradiation increased the expression of ICAM-1 in the middle ear mucosa. Amifostine protected the middle ear from early irradiation injury. There was a relationship between oxygen free radicals derived from irradiation and up-regulation of ICAM-1 expression. Continuous ICAM-1 expression might be related to stenosis of the eustachian tube.