Adjunctive systemic and locally delivered metronidazole in the treatment of periodontitis: a controlled clinical study.

OBJECTIVE: To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole. DESIGN: A single blind randomised clinical trial of 90 subjects, stratified for periodontitis disease severity and smoking status, divided into three treatment groups: 1. Subgingival scaling using ultrasonic scalers and local anaesthesia; 2. Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole (200 mg tds); 3. Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25% metronidazole gel one week apart in all sites with probing depths more than 4 mm. Evaluations were made before treatment, and 8 weeks and 24 weeks post treatment. MAIN OUTCOME MEASURES: Probing depths, probing attachment levels and bleeding on probing were measured using a Florida probe. Bacterial morphotypes were evaluated with darkfield microscopy. Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance. RESULTS: 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter. Mean probing depths were reduced following treatment by greater than 1.6 mm (Group 1 = 1.68 mm, Group 2 = 1.62 mm, Group 3 = 1.74 mm at six months post treatment) but no significant differences were detected between treatment groups at any time point. Similarly, no significant differences were detectable between treatments for changes in mean probing attachment levels, bleeding on probing, plaque scores or proportions of bacterial morphotypes. CONCLUSIONS: This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of periodontitis.

Inhibition of tumor production of granulocyte-macrophage colony-stimulating factor by 1 alpha, 25-dihydroxyvitamin D3 reduces tumor motility and metastasis.

Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma tumors (LLC-LN7) has been shown to increase their migration and invasion in vitro, and metastasis in vivo. The present studies showed that treatment of the LLC-LN7 cells by 2 days culture with 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited their production of GM-CSF. The 1,25(OH)2D3-treated cells also became less migratory and invasive. This inhibitory effect on tumor motility could not be readily reversed upon removal of 1,25(OH)2D3. The mechanism by which 1,25(OH)2D3 reduced tumor motility was attributed to the inhibition of tumor GM-CSF production since the capacity to migrate and invade could be restored by supplementing the medium with recombinant GM-CSF. In vivo studies showed that treatment of LLC-LN7-bearing mice with 1,25(OH)2D3 had no effect on growth of s.c. primary tumors, but reduced the formation of tumor metastases. These results show that 1,25(OH)2D3 can interrupt the autocrine motility-stimulation cascade by reducing tumor production of GM-CSF, thus reducing the expression of properties that are characteristic of metastatic tumor cells.