Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis

OBJECTIVES: The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). METHODS: Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). RESULTS: Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. CONCLUSIONS: The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.     

Keratin 17 gene expression during the murine hair cycle

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels and interferes with the metabolic pathway of TH. To test the hypothesis that DPH affects the enterohepatic cycle of TH and, thus, the kinetics of TH turnover, we performed a kinetic experiment (three-compartment analysis) and a steady-state, double-isotope equilibrium experiment in rats treated for 3 weeks with DPH (50 mg/kg body weight per day) and in untreated controls. This included measurements of TH and TH metabolite levels, as well as the activities of enzymes involved in the TH metabolic pathway. DPH treatment resulted in a decrease in the production of thyroxine (T4) (by 25%) and tri-iodothyronine (T3) (by 37%), a decrease in the T3 concentration in all three pools, and a redistribution of T4 from the fast to the slow pool. The amount of T4 increased in intestinal contents and feces by 66% and 71% respectively. Expressed as a fraction of daily TH disposal, fecal loss of T4 was enhanced from 10 to 23% and that of T3 from 16 to 21%. An increase in T4 and T3 UDP-glucuronyltransferase activities was observed, suggesting that the increased fecal loss of T4 and T3 is secondary to an increased biliary output of their glucuronides. The reduced secretion of TH and increased fecal clearance during DPH treatment can lead in the long run to depletion of TH stores.     

Holistic nursing--definition and realization

Single-channel properties of a delayed rectifier voltage-gated K+ channel (I-type) were investigated in peripheral myelinated axons from Xenopus laevis. Channels activated between -60 and -40 mV with a potential of half-maximal activation, E50, at -47.5 mV. Averaged single-channel currents activated with a time delay at all membrane potentials tested. Time to half-maximal activation decreased from 80 to 1.6 msec between -60 and +40 mV. The channel inactivated monoexponentially with a time constant of 10.9 sec at -40 mV. The time constant of deactivation was 126 msec at -80 mV and 16.9 msec at -110 mV. In symmetrical 105 mM K+, the single-channel conductance (gamma) was 22 and 13 pS at negative and positive membrane potentials, respectively, at 13-15 degrees C. In Na+ -rich solution with 2.5 mM extracellular K+ gamma was 7 pS and the reversal potential was negative to -80 mV, indicating a high selectivity for K+ over Na+. gamma depended on extracellular K+ concentration (KD = 19.6 mM) and temperature (Q10 = 1.45). External tetraethylammonium (TEA) reduced the apparent single-channel amplitude at all potentials tested with a half-maximal inhibiting concentration (IC50) of 0.6 mM. Open probability of the channel, but not single-channel current amplitude was decreased by extracellular dendrotoxin (DTX, IC50 = 6.8 nM). mast cell degranulating peptide (MCDP, IC50 = 41.9 microM). In Ringer solution the membrane potential of macroscopic I-channel patches was about -65 mV and depolarized under TEA and DTX. It is concluded that besides their activation during action potentials, I-channels may also stabilize the resting membrane potential.