Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis.

BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. METHODS: The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. RESULTS: There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. CONCLUSION: The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.

A review of the non-neoplastic kidney effects of hydrocarbon exposure in humans.

This review has demonstrated that there is a considerable amount of information in the medical literature concerning hydrocarbon-associated kidney effects. The existing data lends itself to a variety of divergent interpretations. Ravnskov has stated that "glomerulonephritis should be recognized legally as an occupational disease," yet there is no mention of hydrocarbon exposure in the differential diagnosis of glomerulonephritis in two standard American textbooks of internal medicine. Two recently published textbooks of occupational medicine state without reservation that "studies have linked hydrocarbon exposure to glomerulonephritis" and base this conclusion on the previously cited studies of Beirne and Brennan, Zimmerman, and Ravnskov. Based on this review, the following conclusions have been reasonably substantiated: 1. Massive exposure to petroleum distillates on rare occasions may cause acute renal failure due to tubular necrosis. This appears to be a reversible lesion which, depending on the level of exposure, the medical care and support available, and pre-existing renal function, may be without chronic sequelae. 2. Case reports linking Goodpasture's syndrome and other types of glomerulonephritis to hydrocarbon exposure are based on circumstantial evidence and cannot be used to establish a causal association. 3. The evidence from the eight case-control studies of hydrocarbon exposure and glomerulonephritis is inconclusive. Six of the eight published case-control studies show a positive association between hydrocarbon exposure and glomerulonephritis, but four of the six studies have methodologic flaws that could explain the observed effect. The findings in the one positive study that is methodologically acceptable were not replicated in a subsequent study utilizing a similar design. 4. Studies of hydrocarbon-exposed occupational cohorts have generally revealed a lower than expected risk of death from renal causes. As with most historical cohorts, the specific exposures, intensities and durations of exposure have been poorly defined. Effects of mortality that may occur among highly exposed subsets of these occupational cohorts may be diluted by a relatively large proportion of workers with minimal or no exposure to the class of hydrocarbons in question. 5. Studies of renal biochemistry and renal function effects have been uniformly negative in groups of workers from several industries with relatively high exposures of long duration to a variety of hydrocarbon solvents. The statistically significant differences in proteinuria and cell excretion observed in one of the studies should not be confused with clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

The blood-brain barrier in rats fed on diets high or low in saturated/unsaturated fat ratio.

The product of the permeability x vascular surface rate area (PA) of the blood-brain barrier to [14C]sucrose has been measured in rats raised on synthetic diets in which the saturated/unsaturated fat constitution was controlled at high or low levels. Gas-liquid chromatography demonstrated marked differences in brain fatty acid constitution between the dietary groups. No statistically significant differences was found between the permeability measurements in rats maintained on any of the synthetic diets, nor was there any difference from rats raised on a standard laboratory pellet food. The opportunity was taken to look at 3 other properties of brain that might be affected by lipid constitution. There was no change in the form of the membranous intracellular inclusions that can be induced by intracerebral injections of suramin, and Fink-Heimer staining of degenerating axons, which is inhibited by fat extraction, worked equally well on each diet group. The sleep time after an anaesthetic injection of alcohol was not significantly changed.