Decrease of inorganic blood sulfate following treatment with selected antirheumatic drugs: potential consequence for articular cartilage

The elimination kinetics of inorganic blood sulfate in mice was followed for four hours after a single, oral administration of an antirheumatic drug. Sodium salicylate, aspirin, diflunisal and benorylate, all in a dose of 1.25 mmol/kg, reduced the sulfate level to the less than half that of control. This phenomenon was also demonstrated by phenylbutazone, oxyphenbutazone (both 1 mmol/kg), chloroquine diphosphate (0.6 mmol/kg) and tiaprofenic acid (0.02-0.35 mmol/kg). Niflumic acid (1.08 mmol/kg), piroxicam (0.03 mmol/kg), indomethacin (6.10(-3) mmol/kg), diclofenac (5.10(-3) mmol/kg), ketoprofen (0.2 mmol/kg), naproxen (0.08 mmol/kg) and ibuprofen (0.24 mmol/kg) possessed no sulfate lowering properties. The potential relevance of the use of sulfate lowering drugs for articular cartilage integrity is discussed in the light of what is already known about this subject.     

Effect on cooking time on mutagen formation in smoke, crust and pan residue from pan-broiled pork

The effect of cooking time on mutagenic activity in crust, pan residue and smoke from pan-broiled pork patties was studied in the Ames Salmonella mutagenicity test system. The effect on mutagenicity of reheating the cooked patties and of keeping them warm was also studied. The meat was broiled at 200 degrees C for various times between 2 and 10 min. Broiled meat was reheated up to 5 times at 200 degrees C, each time to a centre temperature of 70 degrees C. Reheating was also performed in a microwave oven for 2 min and in an electric oven at 200 degrees C for 10 min. In addition, broiled patties were kept warm at 60 degrees C in an incubator for up to 9 hr. The mutagenic activity increased rapidly in all fractions except the volatile phase over the first 6 min of cooking, after which time only a slight increase was seen. At cooking times below 4 min no mutagenic activity was detected in the smoke. Reheating or keeping the meat warm for up to 9 hr had very little effect on the mutagenic activity of the meat. Reversed-phase high-performance liquid chromatography mutagenicity profiles of the aerosol, crust and pan-residue extracts showed no major qualitative differences in samples cooked at different times. It is concluded that during pan broiling at 200 degrees C the major part of the mutagenic activity is formed during the first 6 min of cooking. Reheating the meat or keeping it warm does not significantly affect the mutagenic activity. No major additional mutagens are formed during continued heating for up to 25 min.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.     

Phase III clinical trial with a new oral contraceptive containing 150 micrograms desogestrel and 20 micrograms ethinylestradiol.

Results are presented of a Phase III international multicentre trial to study the effect of a new low-dose oral contraceptive (OC) containing 20 micrograms ethinylestradiol and 150 micrograms desogestrel (Mercilon) regarding efficacy, cycle control, blood pressure, and acceptability. Altogether 1,684 women from 12 European countries were included in the study. Four pregnancies occurred, 3 of them patient failures, one tablet failure. The overall Pearl Index was 0.20. The frequency of irregular bleeding was comparable to that recorded with other commonly used low-dose OCs. No serious side effects occurred. The incidence of the most frequently reported subjective side effects--headache, nausea and breast tension--was already low after the first cycle of treatment and decreased to below pretreatment levels with continued use. There was a small increase in mean body weight, which was confined essentially to young women. The preparation did not affect the mean systolic or diastolic blood pressure. This new preparation has thus proved to be an effective, safe and well-accepted ultra low-dose oral contraceptive.     

Dependence of vitamin B-6 status assessment on alcohol intake among elderly men and women (Dutch Nutrition Surveillance System)

To obtain more insight into the effect of moderate alcohol intake on vitamin B-6 status indicators, we studied the associations of alcohol intake (unadjusted and adjusted for intake of vitamin B-6 and protein) with the erythrocyte aspartate aminotransferase activation coefficient (EAST-AC) and plasma pyridoxal 5'-phosphate (PLP) level. Data obtained from men (n = 224) and women (n = 217) aged 65-79 (nationwide sample in the Netherlands) were used for this purpose. Although alcohol intake (a maximum of 21% of the energy came from alcohol) tended to be positively associated with PLP, this association never reached statistical significance (p greater than or equal to 0.05). EAST-AC was inversely associated with alcohol intake, whether or not it was adjusted for vitamin B-6 and protein intake. Similar results were found for the total EAST activity (after adding PLP) or apoenzyme activity; the basal EAST activity (before adding PLP) or holoenzyme activity was not associated with the alcohol intake. These results indicate that caution is needed in the interpretation of the specificity of EAST-AC (i.e., the degree to which EAST-AC is unaffected by other factors) as an indicator of vitamin B-6 intake.