Both interleukin-10 (IL-10) and IL-4 inhibited the prostanoid synthesis of lipopolysaccharide (LPS)-stimulated human monocytes, and their inhibition was shown to be based on a common mechanism to suppress the gene expression of inducible cyclooxygenase (COX). COX has been shown to exist in at least two distinct isoforms, designated COX-1 and COX-2, and their gene expressions exhibit different profiles. At both the protein and mRNA levels, the expression of COX-1 was constitutive and was not modulated by treatments with LPS, IL-10, or IL-4. In contrast, the expression of COX-2 was observed only after stimulation with LPS. IL-10 and IL-4 significantly inhibited LPS-induced COX-2 expression. Kinetic studies showed that they inhibited COX-2 mRNA expression within 1 hour after stimulation and that maximal inhibition was consistently observed at 5 hours. Moreover, the addition of cycloheximide (CHX) to LPS-stimulated monocytes resulted in a superinduction of COX-2 mRNA, whereas CHX almost abrogated the abilities of IL-10 and IL-4 to inhibit this gene expression. Experiments with actinomycin D showed that both cytokines accelerated the degradation of COX-2 mRNA. Furthermore, nuclear run-on experiments showed that both cytokines modestly inhibited LPS-induced COX-2 gene transcription. Thus, both cytokines seemed to regulate the COX-related pathway in a similar manner, although their receptor systems did not show any structural similarities. Considering recent findings showing that the drugs that exhibit a selective effect on COX-2 may be more preferable in inflammatory conditions, such biologic activities of IL-10 and IL-4 described above may offer useful tools in controlling inflammatory disorders in the future.
Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) are thought to be hypersensitivity syndromes with various causes, and radiotherapy might be one of the causes of these syndromes. We herein report two cases of EM/SJS following radiotherapy. The first case was a 63-year-old woman with breast cancer. At the end of postoperative radiotherapy with 60 Gy, severe pruritic erythema appeared in the irradiated area and spread over the whole body. She was diagnosed with EM by a skin biopsy. The second case was a 77-year-old woman with uterine cervical cancer who underwent postoperative radiotherapy. At a dose of 30.6 Gy, pruritic redness appeared in the irradiated area and the precordial region, and it became widespread rapidly with polymorphic transformation. Although without any histological confirmation, SJS was strongly suspected because of her pruritic conjunctivitis. Because both patients were given medicines during irradiation, radiotherapy may not be the only cause of EM/SJS. However, it should be noted that radiotherapy might trigger EM/SJS.
The effects of microinjection of prostaglandin E(2) (PGE(2)) (50 fg-50 ng/0.2 microl) into the ventromedial hypothalamus (VMH) on nociception were studied using a hot-plate test in rats. Microinjection of PGE(2) (5-500 pg and 50 ng/0.2 microl) into the VMH significantly prolonged the paw-withdrawal latency on a hot plate 5 and 10 min after injection, respectively. Maximal prolongation was obtained 5 min after the injection of PGE(2) at 5 pg. Subsequently, to determine whether the PGE(2) receptor subtype EP(1) is involved in the PGE(2)-induced antinociceptive effect in the VMH, we observed the changes in nociception after intraVMH microinjection of SC19220, an EP(1) receptor antagonist, and 17-phenyl-omega-trinor PGE(2), an EP(1) receptor agonist. Simultaneous injection of SC19220 (150 ng) with PGE(2) (500 pg) into the VMH blocked the PGE(2)-induced prolongation of the paw-withdrawal latency. Moreover, an intraVMH microinjection of 17-phenyl-omega-trinor PGE(2) (500 pg) prolonged it. These results indicate that PGE(2) in the VMH has antinociceptive effect through its actions on EP(1) receptors in rats.
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-yearold female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome.
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