Ketoprofen Versus Paracetamol in the Treatment of Acute Migraine

The efficacy and safety of ketoprofen and paracetamol were compared for the treatment of acute migraine in a randomized, double-blind study of 64 patients. Thirty-four patients received ketoprofen 100 mg intramuscularly, and 30 patients received paracetamol 500 mg intramuscularly. Partial or complete relief of pain and other symptoms was achieved 15 to 20 minutes after administration in the ketoprofen group and within 35 minutes in the paracetamol group. Complete relief of pain was achieved within 30 to 40 minutes after ketoprofen in 28 patients (82.5%) compared to 5 patients (17.5%) in the paracetamol group. Six of the patients treated with ketoprofen needed a second dose for complete relief of pain during the 4-hour follow-up period. Side effects were rare and minimal. Our findings suggest that ketoprofen produced statistically significant benefit in the treatment of acute migraine.     

Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis.

Dopamine regulation of the levels of dynorphin, enkephalin, and substance P messenger RNAs in rat striatal neurons was analyzed with in situ hybridization histochemistry (ISHH). Relative levels of peptide mRNA expression in the patch and matrix compartments of the dorsolateral striatum were compared among control rats, rats treated for 10 d with apomorphine, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic system, and rats with nigrostriatal dopaminergic lesions followed 2 weeks later by 10 d of apomorphine treatment. Image analysis of ISHH labeling demonstrated that the number of neurons expressing each peptide mRNA remained constant, whereas the relative level of peptide mRNA per neuron changed significantly, depending on the experimental treatment. Dynorphin mRNA expression increased following chronic apomorphine treatment: striatal patch neurons increased to an average of 100% above control values, whereas striatal matrix neurons showed only a 25% increase. Dynorphin mRNA expression decreased following 6-OHDA lesions: patch neurons showed an average 75% reduction in expression, whereas matrix neurons showed no significant change. In animals with 6-OHDA lesions followed by apomorphine treatment, both patch and matrix neurons showed an average increase in dynorphin expression of 300% above control levels. Changes in dynorphin mRNA levels with these treatments were matched by qualitative changes in dynorphin immunoreactivity both in the striatum and in striatonigral terminals in the substantia nigra. Neither substance P nor enkephalin mRNA levels showed a significant difference between the striatal patch and matrix compartments in any experimental condition (in the dorsolateral striatum). Substance P mRNA expression was increased an average of 50% after 10 d of apomorphine treatment and showed an average decrease of 75% following 6-OHDA lesions of the mesostriatal system. There was no significant change in the expression of substance P mRNA in striatal neurons compared to control values in rats with combined 6-OHDA lesion and apomorphine treatment. Enkephalin mRNA expression was not significantly altered by chronic apomorphine treatment but showed an average increase per cell of some 130% above control levels following 6-OHDA-induced lesions of the mesostriatal system. In animals with a 6-OHDA lesion and apomorphine treatment, enkephalin mRNA was also elevated but not significantly above the levels produced by the lesions alone. These data show that the expression of dynorphin, enkephalin, and substance P is differentially regulated by the mesostriatal dopaminergic system and, further, suggests that the mechanisms by which this regulation occurs may be different for the 3 peptide families.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.