Interferon-beta in pediatric multiple sclerosis patients: safety in short-term prescription

None of the approved immunomodulatory drugs in adults Multiple Sclerosis [MS] patients have been officially approved for the pediatric patients and are currently used off-label in this population. In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a [Avonex[registered]] and subcutaneously injected interferon beta1-b [Betaferon[registered]] in children with definite relapsing-remitting MS [RRMS]. Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonald's criteria, were enrolled in this study. Six patients were treated with Avonex[registered] 30 micro g, intramuscularly every week, and seven patients were treated with Betaferon[registered] 250 micro g, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Eleven girls and two boys, mean [SD] age of 14.7 [1.9] years, were studied. Following nine months of using interferon-beta, nine patients [69.2%] had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children

Effects of 4-[2-Alkylthio-1-benzyl-5-imidazolyl]-dihydropyridines on the isolated rat colon and right atrium contractility

In order to provide a pharmacological profile for some newly synthesized dihydropyridines, we investigated their effects on the isolated rat colon segments and the isolated rat atrium contractility. The tested compounds include alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 2-alkylthio-1-benzyl-5-imidazolyl substituent, and nifedipine as a positive control substance. Isolated rat colon and atrial tissues were prepared. Rat colon was contracted with 80 mM KC1, and maximum response was recorded [100%]. After washing tissue with Krebs solution it was preincubated with different concentrations of test compounds and again KC1 was added and percent change in contraction was calculated. Spontaneous contractions and its frequency for colon and atrium before and after addition of test compounds were also recorded and percent change was calculated. Nifedipine [10[-8]-10[-5] M] was used as positive control at all experiments. The compounds showed similar effects to that of nifedipine on the isolated rat colon. The potency of these analogues with concentration range 10[-5] to 10[-4] M was compared to potency of nifedipine which was effective at 10[-8] to 10[-5] M [P<0.01]. However, unlike nifedipine, the test compounds exerted significant positive inotropic effect on the isolated rat atrium [P < 0.01]. Our observations suggest that these analogues of nifedipine selectively enhance contractility of heart muscle while causing relaxation of intestinal smooth muscle. These compounds may serve as valuable probes to develop novel dihydropyridines with dual smooth muscle relaxant effect and positive inotropic action

effects of genistein, a tyrosine kinase inhibitor on acute and chronic inflammation in diabetic mice

The effects of tyrosine kinases on acute and chronic inflammation during diabetes are not fully determined. Therefore, the present study focuses on the effects of genistein, a tyrosine kinase inhibitor, on acute and chronic inflammation in diabetic mice. The mice either received normal saline [control, 0.1 ml, i.p., n=144] or streptozotocin [diabetic, STZ, 200 mg kg [-1], i.p., n=144]. A week after injection of saline or STZ acute and chronic inflammation was induced by injecting carrageenan and implanting 2 cotton pellets. Before injection carrageenan or 5 day after implantation, 9 mice from each group [control or diabetic] received genistein [10 mg kg [-1], i.p.], indomethacin [2 mg kg [-1], i.p.] or L-NAME [0.1 mg kg [-1], i.p.]. Paw edema and the weight of cotton pellets were significantly higher in diabetic mice. Pretreatment with either indomethacin or L-NAME significantly reduced the acute and chronic inflammation in the diabetic group. Genistein reduced chronic inflammation significantly. These results suggest that activation of tyrosine kinases as well as prostaglandins and nitric oxide pathways are involved in the increased chronic inflammatory responses observed in the diabetic animals

anti-inflammatory effects of aqueous extract of ginger root in diabetic mice

On the basis of reports that ginger [Zingiber officinale, Z. officinale] extract has antiinfalammatory activity, the present study was undertaken to investigate whether the aqueous extract of Z. officinale has any significant beneficial effect on chronic inflammation in diabetic mice. Control mice received normal saline [0.1 ml, i.p.], and in the test group, diabetes was induced by injection of streptozotocin [STZ, 180mg/kg, i.p.] which was confirmed by the measurement of blood glucose, 7 days after STZ injection. One week after saline or STZ injection, chronic inflammation was induced by implantation of cotton pellets [30 mg] on each side of the groin region subcutaneously. Then at the day of 3, the aqueous extract of Z.officinale was added to drinking water [100, 200 and 400 mg/100 ml] for 4 days. In another sets of experiments, L-NAME, a nitric oxide synthase inhibitor, [0.1 mg/kg, i.p.] and indomethacin, an inhibitor of the prostaglandin biosynthesis, [2 mg/kg, i.p.] were injected at the day of 5 of implantation. On the 8th day, the mice were killed and the pellets were removed, freed from extraneous tissue and dried at 60 °C for 24h. The increase in the weight of cotton pellets was higher in diabetic mice [control: 160 +/- 13.6 mg,diabetic: 271 +/- 11.8 mg, P<0.001]. Pretreatment with the aqueous extract of Z. officinale caused a significant but not dose-dependent reduction in cotton pellet weight in diabetic animals [diabetic + Z.officinale's extract: 181.4 +/- 21 mg, P<0.05 vs diabetic]. The anti-inflammatory effect of extract was almost the same as L-NAME, but less than indomethacin. Results suggest that the anti-inflammatory effects of aqueous extract of Z. officinale are comparable to L-NAME