Intraventricular haemorrhage is a major complication of prematurity that results in neurological dysfunctions, including cerebral palsy and cognitive deficits. No therapeutic options are currently available to limit the catastrophic brain damage initiated by the development of intraventricular haemorrhage. As intraventricular haemorrhage leads to an inflammatory response, we asked whether cyclo...

At antipyretic and analgesic doses, salicylate has no antiplatelet or anti-inflammatory effects, unlike typical inhibitors of the prostaglandin H synthases (PGHSs). We demonstrated that salicylate inhibits PGHS-1 and -2 with a potency inversely related to ambient hydroperoxide concentrations. Salicylate inhibition of PGHS-1 was prevented by 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Increa...

T he anesthesiologist has a central role in the management of acute postoperative pain, and effective management has been clearly demonstrated to improve clinical outcomes (1,2). Acute pain can rapidly evolve into chronic pain, and the two should not be viewed as separate entities (3). Failure to achieve effective analgesia is a major predictive factor for the conversion of acute postoperative ...

Over the past several months clinicians have been confronted at an escalating rate with reports describing the risks of COX-2 inhibitors (coxibs). Information on this class of drugs appears not only in traditional medical journals and textbooks, but also on the Web sites of regulatory agencies, professional societies, and pharmaceutical manufacturers.1–9 An unusual, but noteworthy, aspect of th...

High levels of NaCN (20 to 250 mM) were required to inhibit cyclooxygenase catalysis and cause extended lag periods (up to 1.6 min), whereas CO failed to inhibit catalysis. This NaCN inhibition was easily overcome by endogenous or exogenous hydroperoxides. Added hydroperoxides acted to eliminate lag periods without undergoing net conversion to other chemical species. In addition, experiments wi...

OBJECTIVE The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. DESIGN AND METHODS In 20 obese subjects (age 37 ± 12 years, BMI 47 ± 8 kg/m²), subcutaneous and visceral fat were collected during bariatric surgery and characterized for adipose depot-specific gene expression, endothelial cell phenoty...

The increase in cerebral blood flow (CBF) during neuronal activation can be only partially attenuated by individual inhibitors of epoxyeicosatrienoic acids (EETs), cyclooxgenase-2, group I metabotropic glutamate receptors (mGluR), neuronal nitric oxide synthase (nNOS), N-methyl-D-aspartate receptors, or adenosine receptors. Some studies that used a high concentration (500 μM) of the cyclooxygen...

Aspirin-induced asthma is a distinct clinical syndrome which affects about 10% of adult asthmatics. In these patients aspirin and several other analgesics precipitate asthmatic attacks. The idea that the attacks might result from the specific inhibition of a single enzyme, namely cyclooxygenase, has gained both experimental and clinical support. It stimulated a number of hypotheses on the mecha...

The sensitivity of cancer patient macrophages from different anatom ical sites to arachidonic acid metabolism was investigated in tumor cell cytotoxicity assays. Alveolar macrophages and peripheral blood monocytes from 13 non-small cell lung cancer patients, peritoneal macrophages and peripheral blood monocytes from 13 ovarian cancer patients, and comparable macrophages from control patients wi...