Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer results from disturbances of cellular signal transduction and data processing at the genetic and epigenetic level. In the early phase of the disease these disturbances are mainly caused by environmental toxic agents, i.e. genotoxic and non-genotoxic carcinogens, whereas endogenous agents derived from dys-regulated metabolic reactions may take over this role at later stages, thereby leading to a state of 'genetic instability' and 'growth autonomy'. Among these metabolic reactions becoming dys-regulated in the course of tumorigenesis, eicosanoid biosynthesis from arachidonic acid seems to play a particular role. A steadily increasing body of evidence indicates a causal relationship between cancer development and an abnormal overexpression of eicosanoid-forming enzymes, i.e. cyclooxygenases and lipoxygenases, in a wide variety of human and animal tumors. This overexpression seems to result from disturbances of cellular signaling cascades such as the Ras-Raf-MAPkinase cascade due to oncogenic gene mutations. Presently, research is focussed on the proinflammatory enzyme cyclooxygenase-2 (COX-2) the pathological overexpression of which has been found to be related to key events of tumor promotion such as cellular hyperproliferation, inhibition of programmed cell death, and tumor angiogenesis. In the mouse skin model of multistage carcinogenesis COX-2-derived prostaglandin F(2alpha) has been indentified as an endogenous tumor promoter. Moreover, genotoxic byproducts of both cylooxygenase and lipoxygenase-catalyzed arachidonic acid metabolism (such as active oxygen species, free radicals etc.) are suspected to contribute to 'genetic instability' and thus to malignant progression of tumor cells. The enzymes of eicosanoid biosynthesis rank therefore among the most attractive targets for cancer chernoprevention. In fact, both nonsteroidal antiinflammatory drugs, i.e. non-specific COX inhibitors, and isozyme-specific COX-2 inhibitors have been shown to inhibit experimental and human cancer development, in the latter case in particular in the large bowel. Beside their role as indicators of neoplastic development eicosanoids may be also used as reporters of skin irritation. Based to this concept an in vitro test system for skin toxicity has been developed in which the release of arachidonic acid and interleukin-1alpha, i.e. two key mediators of acute inflammation, from a human keratinocyte cell line is measured. The excellent correlation found between this mediator release and the effects of various chemical irritants on human skin in vivo indicates that, in the near future, this and related methods may help to do without animal experiments in toxicological testing.
 ...
PMID:A causal relationship between unscheduled eicosanoid signaling and tumor development: cancer chemoprevention by inhibitors of arachidonic acid metabolism. 1109 Sep 44

Control of early postoperative pain entails the use of various medications including acetaminophen, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, tramadol, and opioids. However, these medications should be carefully administered in patients with aspirin-exacerbated respiratory disease because some medications may trigger adverse reactions after maxillofacial surgeries. The goal of postoperative pain control in patients with aspirin-exacerbated respiratory disease is to eliminate pain without complications. Local anesthesia is an efficient tool for the control of postoperative pain after maxillofacial surgeries. We utilized a transdermal drug delivery system, iontophoresis by alternating current, in order to develop an alternative technique for administering local anesthetic to control postoperative pain in 2 patients with aspirin-exacerbated respiratory disease. A visual analogue scale was used to objectively measure the severity of pain. A 55-year-old woman who underwent mandibular wisdom tooth extraction and an 18-year-old woman who underwent sagittal split ramus osteotomy of the mandible both complained of pain multiple times. After application of iontophoresis, the visual analogue scale score was reduced to zero and postoperative pain could be controlled. There were no adverse events such as bronchospasm or skin irritation after the application of iontophoresis by alternating current.
 ...
PMID:Alternating Current Iontophoresis for Control of Postoperative Pain. 2995 52