Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome.

OBJECTIVE: In the absence of comparative trials a meta-analysis was performed to compare the efficacy and tolerability of the non-ergot derived dopamine agonists, pramipexole and ropinirole, in restless legs syndrome (RLS). METHODS: Frequentist fixed and random-effects models were pre-specified for the direct comparisons and a Bayesian approach for the indirect comparison. Efficacy outcomes included the mean change from baseline in the International RLS Study Group Rating Scale (IRLS) score and the percentage of responders on the clinical global impressions - improvement scale (CGI-I). Safety outcomes included the incidence of withdrawal and adverse events. RESULTS: The direct meta-analysis confirmed superior efficacy for both treatments versus placebo for the IRLS (pramipexole: -5.45; 95% CI: -7.70; -3.20; ropinirole: -3.16; 95% CI: -4.26; -2.05) and the CGI-I (pramipexole: OR=2.98; 95% CI: 2.08; 4.26; ropinirole: OR=1.99; 95% CI: 1.52; 2.60). Placebo comparisons showed a significantly higher incidence of nausea for pramipexole (p<0.01), whereas nausea, vomiting, dizziness, and somnolence were significantly higher for ropinirole (all p<0.01). The indirect comparison showed with a probability of > or = 95%, a superior reduction in the mean IRLS score (-2.33; 95% credibility interval [CrI]: -4.23; -0.41), higher CGI-I response rate (OR=1.50; 95% CrI: 0.97; 2.32) and significantly lower incidence of nausea, vomiting, and dizziness for pramipexole compared to ropinirole. CONCLUSION: Differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed. These findings should be further confirmed in head-to-head clinical trials.

Oral meloxicam is effective in acute sciatica: two randomised, double-blind trials versus placebo or diclofenac.

OBJECTIVE: Two randomised, double-blind, double-dummy trials evaluated the efficacy and tolerability of meloxicam compared with placebo or diclofenac in patients with acute sciatica. SUBJECTS: 1021 patients with acute sciatica. TREATMENT AND METHODS: In the first study, 532 patients received meloxicam 7.5 mg, meloxicam 15 mg, or placebo for 7 days. The second study randomised 489 patients to meloxicam 7.5 mg, meloxicam 15 mg, or diclofenac 150 mg for 14 days. RESULTS: Meloxicam 7.5 mg and 15 mg significantly improved overall pain between baseline and day 7 (p < 0.05) compared with placebo. Furthermore, both meloxicam doses showed similar improvements on all primary and secondary efficacy endpoints compared with diclofenac 150 mg. No significant differences in tolerability were observed between any of the treatment groups in either study. CONCLUSIONS: Meloxicam (7.5 mg or 15 mg) was well tolerated and was more effective than placebo, and as effective as diclofenac, in acute sciatica.

Taurine analog modulation of taurine uptake by two different mechanisms in cultured glial cells.

Previous data have shown that HEPES, a taurine structural analog, inhibits the uptake of taurine by cultured cells differently, depending on its addition either to the culture medium or to the Krebs-Ringer buffer used for cell incubation during taurine uptake measurements (Lleu and Rebel, J Neurosci Res 23: 78-86, 1989). An extensive study of the effect of numerous other taurine structural analogs on taurine uptake by cultured glial cells was carried out. Our results show that taurine uptake modulation by structural analogs follows two different mechanisms. For the first mechanism, observable after the simultaneous presence of taurine and of its analog during the incubation time of the uptake experiment (10 min), the amine function on the molecule is essential. The sulfonate group could be replaced either by a sulfinic group or by a carboxylic group. beta-Alanine, hypotaurine, acetyltaurine, guanidinoethanesulfonate and guanidinopropionate are the most potent inhibitors in this first mechanism. For the second mechanism, which requires the presence of the analog in the culture medium during the 48 hr preceding the taurine uptake measurement, the simultaneous presence of an amine and of a sulfonate group or of an amine and a sulfinate group is required. Carboxylates are ineffective in modulating taurine uptake in this mechanism. The sulfonate buffers synthesized by Good et al. (Biochemistry 5: 467-477, 1966) also affect taurine uptake in both mechanisms.

Phospholipid methylation and taurine content of synaptosomes from cerebral cortex of developing rat.

Changes in taurine concentration and rate of methylation of phosphatidylethanolamine have been examined in rat brain synaptosomes over the course of development. At 7, 14, 21, 28 and 56 days of age, rats were injected i.p. with 300 microCi/kg [3H-methyl]methionine. Synaptosomes (P2B fraction) were isolated from the cerebral cortex 9 h later and incorporation of the methionine methyl group into phospholipid and protein was investigated. Synaptosomal taurine and methionine concentrations were determined at the same ages, as were the concentrations of the major classes of phospholipids (phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine and phosphatidylserine). Methionine concentration increased between day 7 and 14 and fell thereafter. Phospholipid methylation rates calculated from the specific activity of synaptosomal methionine were high from days 7 and 14 and then fell, whereas protein methionylation increased between day 7 and 28 and then decreased. A strong correlation was found between the taurine concentration of the synaptosome and phospholipid methylation rates during brain development. Protein methionylation rates, however, showed no correlation with taurine concentration.

Interference of Good's buffers and other biological buffers with protein determination.

Interference of low concentrations of Hepes and other buffers commonly used in protein determination was studied. The data show that some of these buffers interfere to differing degrees with protein determination according to the Lowry method. A study of the structure-interference relationship suggests that the group ethanolamine is involved in this interference. No interference was observed when protein was measured using bicinchonic acid at the same concentration as the Lowry reagent.

Effect of HEPES on the Na+,Cl-dependent uptake of taurine and beta-alanine by cultured glial cells. Modulation by composition and osmolarity of medium.

The effect of HEPES on the Na+,Cl-dependent uptake of taurine and beta-alanine by cultured glial cells was investigated. Whatever the culture medium used, a similar inhibition of the uptake of taurine by HEPES was found. In a previous paper it was shown that this buffer was able to inhibit the uptake of taurine through a slow and a fast "mechanism", when present in the culture or in the incubation medium, respectively. Comparison of the effect of HEPES on the uptake of taurine and beta-alanine suggested that only the slow "mechanism" was common to the uptake of the beta-aminoacid. Therefore, the uptake of the beta-aminoacid might be affected by HEPES. On the other hand, a small increase of the osmolarity of the media altered the uptake of taurine, suggesting that caution is needed when interpreting pharmacological experiments.

Effect of HEPES on the taurine uptake by cultured glial cells.

HEPES inhibited the taurine uptake in glial cells. A different kind of inhibition was observed when HEPES was present in the culture medium or in the incubation medium used for the taurine-uptake measurement. As an example of a possible interference of HEPES in pharmacological experiments, we have studied the effect of this buffer on the modulation of taurine uptake by beta agonists or ionic concentration.