Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells

Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1ß-stimulated expression of matrix metalloproteinases (MMP)-3 and MMP-1 in human tendon-derived cells. We have now tested additional fluoroquinolones and investigated whether they have a similar effect on expression of MMP-13. Tendon cells were incubated for two periods of 48?h with or without fluoroquinolones and IL-1ß. Total ribonucleic acid (RNA) was assayed for MMP messenger RNA by relative quantitative reverse transcriptase polymerase chain reaction, with normalization for glyceraldehyde-3-phosphate dehydrogenase mRNA. Samples of supernatant medium were assayed for MMP output by activity assays. MMP-13 was expressed by tendon cells at lower levels than MMP-1, and was stimulated typically 10- to 100-fold by IL-1ß. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1ß-stimulated MMP-1 mRNA expression. Both the inhibition of MMP-13 and the potentiation of MMP-1 expression by fluoroquinolones were accompanied by corresponding changes in IL-1ß-stimulated MMP output. The non-fluorinated quinolone nalidixic acid had lesser or no effects. Fluoroquinolones show contrasting effects on the expression of the two collagenases MMP-1 and MMP-13, indicating specific effects on MMP gene regulation

The effects of elemental diet and subsequent food reintroduction on rheumatoid-arthritis

The role of diet in rheumatoid arthritis (RA) remains controversial and there have been no controlled studies on the use of elemental diet in the treatment of RA. Elemental diet is an hypoallergenic protein-free artificial diet consisting of essential amino acids, glucose, trace elements and vitamins. This study was carried out to assess the role of elemental diet and subsequent food reintroduction in RA. Elemental diet (E028) (and a small number of foods) was given to 24 patients with definite RA in order to induce a remission and then foods were gradually introduced. Where a food was suspected of causing symptoms it was removed from the diet. Twenty-three control patients supplemented their usual diet with E028. After the elemental diet there was a statistically significant improvement in the diet group in grip strength (P = 0.008) and Ritchie score (P = 0.006) but not in ESR, CRP, thermographic joint score or functional score. The diet group lost more weight than the control group and this correlated with the improvement in grip strength. This improvement was not present following food reintroduction. As the improvements took place in more subjective disease parameters and because of the difficulties in adequately blinding studies of diet in arthritis. a placebo effect must be considered. There was a high default rate, only 38% of those patients originally enrolled completed the study. In conclusion, this study shows that elemental diet can cause an improvement in a number of disease parameters in RA but this is not sustained by an individualized diet. It also illustrates some of the difficulties involved in the study of diet in arthritis