In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA).

Animals↗

PubMedDate not supplied

Renal aluminum excretion.

Urinary aluminum (Al) excretion was studied in humans with normal and impaired renal function. Al was measured by atomic absorption spectrometry. In healthy volunteers (n = 50), renal Al excretion was 12.2 +/- 8.5 micrograms/24 h. Two patients on plasma exchange therapy with normal renal function and an inadvertent load of 870 and 388 micrograms Al/treatment showed a 23 and 14% positive balance until next treatment. The renal pathway of excretion was shown to be important in 6 chronic renal failure patients on continuous peritoneal dialysis with residual renal function who eliminated in 24 h 51.4 +/- 24.0 micrograms Al by urine and only 27.2 +/- 18.4 micrograms Al across the peritoneum following a daily oral application of 342 mg Al. Studies with the isolated perfused rat kidney confirmed the limited renal capacity to eliminate Al. Al clearance declined from 0.75 to less than 0.08 mL/min when the kidney was perfused with 0.04-12.4 micrograms Al/mL medium. Al content of the kidney increased in a dose-dependent manner from less than 0.05 to 4.4 micrograms/kidney and reached saturation at 5 micrograms Al/mL medium.

Adult↗

PubMedDate not supplied

Analysis of gene expression in lung and thymus of TCDD treated C57BL/6 mice using differential display RT-PCR.

The differential display RT-PCR technique offers a means to identify genes which are regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment of female C57BL/6 mice with 10 micrograms TCDD/kg body weight followed by DDTR-PCR analysis with a set of different primers revealed differential expression for a number of mRNAs. RNA slot blot analysis of six of these clones confirmed differential expression. Further characterization of one of these clones obtained from lung tissue demonstrated that the corresponding mRNA is about 1 kb and shows significant TCDD induced expression in Northern blot analysis. A Genbank search of this clone showed no similarity to known sequences.

Animals↗

PubMedDate not supplied

Neural tube defects: British vitamin trial starts slowly.

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Clinical Trials as Topic↗

PubMedDate not supplied

Artificial reproduction: unrestrictive guidelines for UK.

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Advisory Committees↗

PubMedDate not supplied

Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men.

Genetic factors that could mediate the pathogenesis of male reproductive disorders are largely unclear. Polymorphisms of cytochrome P4501A1 (CYP1A1), a key enzyme in the extrahepatic metabolism of lipophilic xenobiotics, have been shown to influence susceptibility to xenobiotics. Here, CYP1A1 polymorphisms were investigated in 134 infertile Caucasian men. The frequencies of the Mspl polymorphism in the 3'-flanking region of the CYP1A1 gene and a mutation in exon 7 causing an isoleucine-valine exchange (IVE) in the heme-binding region of the enzyme were increased among infertile men when compared with those of unselected, healthy male controls (odds ratio (OR)) 1.4, Cl95 0.68-2.89 for Mspl polymorphism; OR 2.4, Cl95 0.83-6.95 for IVE). Patients with normozoospermia revealed the highest frequencies for both polymorphisms (n = 8; OR 4.5, Cl95 0.97-20.91 for Mspl polymorphism; OR 13.7, Cl95 2.53-74.13 for IVE). ORs for the IVE exceeded the values calculated for the Mspl polymorphism. These preliminary results suggest that genetic variation in the metabolism of xenobiotics may codetermine individual susceptibility to infertility.

Cytochrome P-450 CYP1A1↗

PubMedDate not supplied

Gross and microscopic lesions in young chickens experimentally infected with Salmonella enteritidis.

One-day-old and 7-day-old specific-pathogen-free chickens were orally infected with a field isolate of Salmonella enteritidis phage type 13A. Chickens were sequentially euthanatized at various intervals until 42 days of age, and selected tissues were collected for microscopic evaluation. Eleven of 53 chickens (21%) infected at 1 day of age and 2 of 28 chickens (7%) infected at 7 days of age died. Gross and microscopic lesions were more frequent and severe in chickens infected at 1 day of age and in chickens that died (almost all of these were 1-day-infected as well). Lesions were characterized by mild to severe fibrinous pericarditis, airsacculitis, perihepatitis, peritonitis, cecal cores, and enlarged, firm yolk sacs. Gross the microscopic lesions were present from postinoculation day 2 until termination of this study.

Animals↗

PubMedDate not supplied

Protection by selenoprotein P in human plasma against peroxynitrite-mediated oxidation and nitration.

In order to study functions of selenoprotein P in human plasma, its level was lowered via two techniques, chromatography on Sepharose-bound heparin, or immunoprecipitation; Western blot analysis showed that both techniques were effective at substantially lowering selenoprotein P levels in plasma. When peroxynitrite was infused to maintain a 0.9 microM steady-state concentration, plasma made deficient in selenoprotein P diminished benzoate hydroxylation significantly less than control plasma. Similar differences were found for protein 3-nitrotyrosine formation, determined by Western blot analysis. Conversely, in a selenoprotein P-enriched plasma preparation obtained via heparin-Sepharose chromatography, protection against benzoate hydroxylation was above controls. Likewise, a supernatant from control plasma that had been exposed to anti-selenoprotein P antibodies was less efficient in preventing oxidation and nitration reactions of peroxynitrite than the supernatant from plasma exposed to a non-specific antibody (rabbit anti-sheep IgG). These data demonstrate a role of selenoprotein P in human plasma in the defense against peroxynitrite.

Blotting, Western↗