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This study was initiated to investigate the mechanism of action of a new indomethacin derivative, indomethacin-phenylalanine (indo-Phe) in human monocytes. We determined the effect of indo-Phe on the induction by LPS of prostaglandin-E2 (PGE2) and interleukin-1beta (IL-1beta) production in human monocytes. Indomethacin and indo-Phe inhibited the PGE2 synthesis in treated and untreated IL-1beta or LPS-treated monocytes. Furthermore, in IL-1beta and LPS-treated monocytes, prostaglandin G/H synthase-1 (PGHS-1) protein expression was down-regulated with indomethacin or its indo-Phe analog whereas the level of the inducible protein (PGHS-2) was up-regulated. We analyzed the effect of indomethacin and indo-Phe on the expression of IL-1beta protein in LPS-treated monocytes and found that indo-Phe blocked the LPS-induction of IL-1beta synthesis while indomethacin did not. These differential effects of indomethacin and indo-Phe suggest that two independent ways are involved in the stimulation of monocytes by LPS: the PGHS-2 protein induction and the IL-1beta secretion.

Everyone will agree that specialized computer programs have done away with the many tedious tasks associated with manually keeping track of radioisotopes. Enhanced electronic programs have virtually cut the time of managing radioisotopes. Agriculture and Agri-Food, Canada's (AAFC) program for the management of radioisotopes, is somewhat different from most electronic programs. It is divided into three levels of management that are dependent on the roles that a user might have when applying the application. These roles include the Departmental Radiation Safety Officer (DRSO), Radiation Safety Officer (RSO), and authorized user, which meets the requirements of the Canadian Nuclear Safety Commission. The DRSO and authorized AAFC Radiation Safety Committee members have access to the first level of management. This is the highest level of control, and only the DRSO has permission to add a nuclear substance to the system with the approval of the Canadian Nuclear Safety Commission (CNSC). This level of management is also responsible for adding authorized users, locations, and managing the Internal Use Permits. The second level of management is for site-specific RSOs. They have access to all information regarding their center of activity, but they cannot change Internal Use Permit data. The RSOs can reset passwords, authorize new users, control the maximum activity limit, etc., but are limited to viewing only the information that relates to their internal use permit. However, they retain significant control within the permit. The third and last level of management is for authorized users who can access the radioisotope order-distribution-disposal section, waste or storage containers creation file, and leak/wipe test procedures. As in the case of the DRSO and RSO, they also have access to all reports and inventories for their center of activity but they cannot change Internal Use Permit or inventories data. This program has proven to be a valuable tool for scientific staff in achieving compliance and solving issues of non-compliance in the overall management of radioisotopes.

It has been reported in the literature that Neisseria gonorrhoeae DNA is modified by the methyltransferases (MTases) M· Ngo I, M· Ngo II, and M· Ngo III, as well as three other cytosine MTases and one adenine MTase, even if the corresponding restriction endonucleases are not present. We envisioned the possibility of cloning one of the N. gonorrhoeae MTase-encoding genes for use as a species-specific DNA probe. We therefore undertook a survey of methylation patterns of several clinical isolates of N. gonorrhoeae and N. meningitidis as well as ATCC strains of other Neisseriae. We found, from digestion patterns with isoschizomers, one N. gonorrhoeae strain that lacked M· Ngo III. All N. meningitidis strains (save one) were resistant to digestion with Nla IV thus possessing an MTase like Ngo V, and one was resistant to Sst II, thus having an Ngo III-like MTase. None were resistant to isoschizomers of Ngo I, Ngo III and NgoIIV . Some other Neisseriae had an MTase with Nla IV ( Ngo V) specificity, but none had Ngo I, II, III or IV specificity, except for the Branhamella -like N. caviae-ovis group and N. lactamica where these specificities were present in at least one strain of this group. Therefore, among the Neisseriae other than N. caviae only M· Ngo I is N. gonorrhoeae -specific.