4-(6-Methoxy-2-naphthyl)butan-2-one and related analogues, a novel structural class of antiinflammatory compounds.

A series of compounds related to 4-(6-methoxy-2-naphthyl)butan-2-one has been prepared and tested for antiinflammatory activity by the cotton pellet granuloma method. Compounds possessing a small lipophilic group such as methoxyl, methyl, or chloro in the 6 position in conjunction with a butan-2-one side chain in the 2 position of the naphthalene ring were most active. The indtroduction of a methyl group along the side chain was invariably deleterious. Good activity was generally retained by forming esters of a butan-2-ol side chain.

Blood changes in experimental arthritis in two types of genetically different rats.

1. Rats genetically resistant to dextran and other agents producing the anaphylactoid reaction (NR rats), have a higher polymorph count than do rats which react to these agents (R rats).2. NR rats do not develop polyarthritis when a hind paw is injected intradermally with Freund's adjuvant.3. The polyarthritis produced by an intravenous injection of Mycoplasma arthritidis culture develops more slowly in NR rats than in R rats.4. It is not clear whether the higher polymorph count in NR rats is a main factor in determining their resistance to adjuvant-induced arthritis.

A study of the effects of nabumetone (BRL 14777), a novel anti-inflammatory drug, on cell infiltration into sterile cotton pellets implanted in rats.

Nabumetone a new non-steroidal anti-inflammatory drug is active in reducing the DNA content of implanted cotton pellets in rats on various dosing regimens. The effect of nabumetone can be seen during the early and late phases of the cellular reaction to the implant implicating effects upon polymorphonuclear leucocytes and monocytes. The levels of two lysosomal enzymes are reduced in the exudate by the drug treatment.

Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent.

Nabumetone is a compound of novel structure which displays acute anti-inflammatory activity in the carrageenan-induced oedema model in rats and the ultraviolet-induced erythema model in guinea-pigs. Its activity in these tests is greater than that of aspirin but less than that of naproxen and indomethacin. In the cotton pellet-induced granuloma model in the rat, the compound is active and produces no signs of toxicity at doses much greater than the lowest effective dose, unlike aspirin, naproxen or indomethacin. Nabumetone is also active in the adjuvant-induced arthritis test in rats. In contrast to aspirin, indomethacin and naproxen, the compound is well tolerated by the stomach of fasted rats at doses in excess of those with anti-inflammatory activity. These findings could be linked to the relatively poor ability of nabumetone to inhibit the synthesis of prostaglandins in vitro and to its non-acidic structure. The compound has greater mild analgesic activity than paracetamol, is equi-active with phenylbutazone, but less active than aspirin, naproxen and indomethacin. Nabumetone also has antipyretic activity in the rabbit. No interactions with the hypothalamic-pituitary-adrenal axis have been found.

The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs.

The ability of several non-steroidal acidic anti-inflammatory drugs to cause ulceration when given as copper complexes has been examined. The damage caused by clopirac, niflumic acid and aspirin was virtually abolished when they were given as copper complexes whereas the damage caused by indomethacin, ketoprofen and (+)-naproxen was unaltered. The lack of ulceration with three of these preparations appeared to be correlated with a much reduced ability to inhibit prostaglandin synthesis as determined using an in vitro enzyme system.

Common bile duct in children: sonographic dimensions.

PURPOSE: To determine the normal caliber and rate of growth of the extrahepatic biliary ducts in the pediatric population. MATERIALS AND METHODS: The diameter of the common bile duct was measured with sonography in 173 children aged 1 day to 13 years (mean, 6.0 years; median, 5.0 years) who were examined for reasons other than hepatic or biliary tract disease. Results were subjected to regression analysis and compared with similar measurements of the extrahepatic portal vein and hepatic artery. The size of the gallbladder was subjectively estimated as distended, moderately full, and contracted. Differences in the diameter of the common bile duct in these three groups were evaluated with the Mann-Whitney U test. RESULTS: The average diameter of the common bile duct in this population was 1.27 mm +/- 0.67 (< 3.3 mm in all patients and < 1.2 mm in children aged 3 months or less). The slope of the curve describing the growth of the common bile duct was relatively flat, similar to that of the hepatic artery and half that of the portal vein. There was a significant difference in the diameter of the common bile duct between patients with distended gallbladders and those with contracted gallbladder (P = .02). CONCLUSION: The pediatric common bile duct is significantly smaller than adult norms; it is a distensible structure responsive to fluctuations in prandial bile flow.