Exploiting dispersion of higher-order-modes using M-type fiber for application in mid-infrared supercontinuum generation.

M-type fibers have the exceptional property that the higher-order LP0n modes are core-confined and easily excited, while the LP01 and other modes are confined to a high-index ring surrounding the core, so they are not easily excited. This has profound consequences for mid-infrared supercontinuum sources, where the high zero-dispersion wavelength of chalcogenide and ZBLAN fibers means that exotic pump sources have so far been necessary. We show here that in chalcogenide and ZBLAN M-type fibers the lower ZDW of the core-confined higher-order LP02 mode can be in the range of 2 to 3 µm (around 1.55 µm), while the fiber still has a large core diameter and thus supports high average power. This will allow established pump laser technology to be used in future high-power mid-infrared supercontinuum sources.

Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey.

1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 (COX-2) inhibitor, was investigated in mouse, rabbit, the EM (extensive) and PM (poor metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species differences were evident in the disposition of celecoxib. After intravenous (i.v.) administration of [14C]celecoxib, the major route of excretion of radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral administration, faeces were the primary route of excretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder of the dose excreted in the urine. After oral administration of [14C]celecoxib to the female mouse, radioactivity was eliminated equally in urine (45.7%) and faeces (46.7%). 3. Biotransformation of celecoxib occurs primarily by oxidation of the aromatic methyl group to form a hydroxymethyl metabolite, which is further oxidized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog and monkey was the carboxylic acid metabolite of celecoxib.

Pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib in rats.

The pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide, a cyclooxygenase-2 inhibitor, were investigated in rats. Celecoxib was metabolized extensively after i.v. administration of [(14)C]celecoxib, and elimination of unchanged compound was minor (less than 2%) in male and female rats. The only metabolism of celecoxib observed in rats was via a single oxidative pathway. The methyl group of celecoxib is first oxidized to a hydroxymethyl metabolite, followed by additional oxidation of the hydroxymethyl group to a carboxylic acid metabolite. Glucuronide conjugates of both the hydroxymethyl and carboxylic acid metabolites are formed. Total mean percent recovery of the radioactive dose was about 100% for both the male rat (9.6% in urine; 91.7% in feces) and the female rat (10.6% in urine; 91.3% in feces). After oral administration of [(14)C]celecoxib at doses of 20, 80, and 400 mg/kg, the majority of the radioactivity was excreted in the feces (88-94%) with the remainder of the dose excreted in the urine (7-10%). Both unchanged drug and the carboxylic acid metabolite of celecoxib were the major radioactive components excreted with the amount of celecoxib excreted in the feces increasing with dose. When administered orally, celecoxib was well distributed to the tissues examined with the highest concentrations of radioactivity found in the gastrointestinal tract. Maximal concentration of radioactivity was reached in most all tissues between 1 and 3 h postdose with the half-life paralleling that of plasma, with the exception of the gastrointestinal tract tissues.

Quantitative light microscopic localization of [3H]naltrindole binding sites in the rat brain.

The binding of radiolabeled naltrindole ([3H]NTI), a selective delta-opioid antagonist, was characterized using receptor autoradiography. Receptor binding properties were established in brain paste slices which demonstrated one site receptor occupancy with an apparent Kd of 0.25 +/- 0.08 nM (Bmax of 597.5 fmol/mg protein). Autoradiographic localization of [3H]NTI binding sites in the rat brain revealed high densities of these sites in the cortex (layers 1-3 and 6), caudate putamen, accumbens, claustrum, and internal plexiform layer of the olfactory bulb. Moderate to low levels of specific binding were observed in the hippocampus, thalamus, and substantia gelatinosa of the spinal cord.