Hydroacylation of simple alkenes with aldehydes via a radical process was successfully achieved by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst. Thus, 5-tridecanone was ...obtained by the reaction of oct-1-ene with pentanal in the presence of small amounts of NHPI and dibenzoyl peroxide (BPO).
Adenosine has anti-inflammatory activity. Adenosine deaminase (EC 3.5.4.4) metabolizes extracellular adenosine, resulting in an exacerbation of inflammation. Consequently, it was hypothesized that ...adenosine deaminase inhibitors produce anti-inflammatory activity by increasing extracellular adenosine concentration. This group recently developed a non-nucleoside adenosine deaminase inhibitor, FR234938, by using rational structure-based drug design. FR234938 inhibits recombinant human adenosine deaminase enzyme competitively. FR234938 inhibits interleukin (IL)-6-dependent immunoglobulin (Ig) M production by SKW6.4 cells, in the presence of adenosine. Inhibitory effect of FR234938/adenosine combination is blocked by an A2a adenosine receptor antagonist. FR234938 also inhibits anti-type II collagen delayed type hypersensitivity (DTH) in a dose-dependent manner, both in the presence and absence of recombinant human adenosine deaminase. Moreover, FR234938 inhibits tumor necrosis factor (TNF)-α and IL-10 production in a lipopolysaccharide (LPS)-induced cytokine production model in mice. These results indicate that FR234938 has potential anti-inflammatory activity. Non-nucleoside adenosine deaminase inhibitor FR234938 has good potential as a new type of anti-rheumatic and anti-inflammatory drug, by modulating host-defense concentrations of adenosine.
A study was designed to investigate hyperperfusion syndrome after the restoration of normal cerebral blood flow in a chronically cerebral ischemic state resulting from high-flow arteriovenous ...malformations or severe carotid stenosis. A fistula between the left distal common carotid artery and the jugular vein was created and the left vertebral artery was simultaneously occluded in 44 cats to produce a chronic cerebral ischemic state. For control experiments, 10 cats underwent occlusion of the left common carotid and vertebral arteries. Six weeks later, pial arterial behavior, disruption of the blood-brain barrier (BBB), and cerebral histological changes were investigated using three experimental methods. In the first, in which a fistula was occluded under normal conditions, pial arteries contracted to some 80% of the resting state; however, no BBB disruption or histological changes were observed. In the second experiment, in which a 20-minute occlusion of the left middle cerebral artery was performed in the cats with a patent fistula, a 30% to 40% dilated state of the pial arteries continued after recirculation, and BBB disruption-induced cerebral edema and infarction were observed. These findings were more prominent in the cats that underwent occlusion of the fistula. On the other hand, in the control group, the pial arteries returned to resting size within 40 minutes, and no BBB disruption or histological changes were observed. In the third experiment, in which moderate hypertension was induced for 1 hour, the pial arteries dilated much more remarkably; BBB disruption and cerebral edema were revealed to be more extensive in the cases of fistula occlusion than within those with a patent fistula. In the control group, however, the pial arteries contracted 10% during hypertension, while BBB disruption and histological changes were not evident. The results indicate that the perfusion pressure breakthrough threshold in the chronically ischemic brain may not be reduced by the restoration of normal blood flow, but may be decreased by the addition of new ischemic insults or hypertension.
