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60. Differential effects of paclitaxel and derivatives on guinea pig isolated heart and papillary muscle

Author

Alloatti, G., Penna, C., Gallo, Mp, Levi, Rc, Bombardelli, E., and Giovanni Battista APPENDINO

Subjects
Paclitaxel, Guinea Pigs, Action Potentials, Arrhythmias, Cardiac, Heart, Docetaxel, In Vitro Techniques, Papillary Muscles, Membrane Potentials, Vasodilation, Heart Rate, Coronary Circulation, Animals, Taxoids
Abstract

Paclitaxel (Taxol) is an anticancer agent with clinical activity against various human cancer types. Paclitaxel blocks cell division by stabilizing microtubules, a mechanism that also underlies its major side effects (neutropenia and neurotoxicity). Paclitaxel can also alter cardiac function, and to elucidate the mechanism of this activity, we tested the mechanical and electrical effects of paclitaxel and a series of analogs (docetaxel, taxol B, taxol C and N-methyltaxol C; 5-20 microM) on two different cardiac preparations, the isolated coronary perfused heart and the papillary muscle of the guinea pig. Paclitaxel and N-methyltaxol C induced conduction arrhythmias and reduced coronary flow and left ventricular systolic pressure in the isolated heart, whereas the other taxol derivatives tested had no significant effect. Moreover, paclitaxel blocked the vasodilator effect of bradykinin in the isolated heart. Paclitaxel and N-methyltaxol C produced a positive inotropic effect in papillary muscle, without alterations in the action potential. In the latter preparation, no significant variations were observed after treatment with the other taxol derivatives. The in vitro cardiodepressant and arrhythmogenic activity of paclitaxel is similar to that reported after its clinical administration and might be due to coronary vasoconstriction. The precise role of microtubules as modulators of intracellular calcium in cardiac and smooth muscle cells is at present unclear, because docetaxel and other taxol analogs, though they exhibited similar activity on tubulin, lacked cardiac effects.

Published
1998

62. BASIC RESEARCH

Author

Razvodovsky, Y., primary, Borodinsky, A., additional, Pascual-Mora, M., additional, Pla, A., additional, Renau-Piqueras, J., additional, Guerri, C., additional, Haass-Koffler, C., additional, Kenna, G., additional, Henry, A., additional, Bartlett, S., additional, Dudek, M., additional, Abo-Ramadan, U., additional, Hyytia, P., additional, Maccioni, P., additional, Gessa, G. L., additional, Thomas, A., additional, Malherbe, P., additional, Mugnaini, C., additional, Corelli, F., additional, Colombo, G., additional, Vargiolu, D., additional, Loi, B., additional, Lobina, C., additional, Zaru, A., additional, Carai, M., additional, Riva, A., additional, Bombardelli, E., additional, Morazzoni, P., additional, Osna, N., additional, Kharbanda, K., additional, McVicker, B., additional, Casey, C., additional, Mercer, D., additional, Naassila, M., additional, Legastelois, R., additional, Alaux-Cantin, S., additional, Houchi, H., additional, Botia, B., additional, Pronko, P. S., additional, Khomich, T. I., additional, Satanovskaya, V. I., additional, Karaedova, L. M., additional, Borodinsky, A. N., additional, Lis, R. E., additional, Feltmann, K., additional, Steensland, P., additional, Ledesma, J. C., additional, Bali, P., additional, Gonzalez, C., additional, Aragon, C., additional, Etelalahti, T., additional, Eriksson, P., additional, Todkar, A., additional, Granholm, L., additional, Comasco, E., additional, Oreland, L., additional, Hodgins, S., additional, Nilsson, K., additional, Nylander, I., additional, Phedina, K., additional, Zimatkin, S., additional, Smutek, M., additional, Parkitna, J. R., additional, Przewlocki, R., additional, Janeczek, P., additional, Van Steenwyk, G., additional, Lewohl, J., additional, Napper, R., additional, Hopping, M., additional, Stragier, E., additional, Massart, R., additional, Hamon, M., additional, and Lanfumey, L., additional

Published
2013
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64. The effect of ginger (Zingiber officinalis) and artichoke (Cynara cardunculus) extract supplementation on gastric motility: a pilot randomized study in healthy volunteers.

Author

LAZZINI, S., POLINELLI, W., RIVA, A., MORAZZONI, P., and BOMBARDELLI, E.

Abstract

OBJECTIVE: Prodigest® is the standardized combination of artichoke and ginger extracts. This combination was safe and effective in the treatment of functional dyspepsia. However, further evidence could be useful to shed new lights on the effect of Prodigest® on gastric motility. This pilot randomized study on healthy volunteers investigates the prokinetic activity of Prodigest®. SUBJECTS AND METHODS: This was a randomized, cross-over study in healthy volunteers comparing Prodigest® versus placebo. Eleven healthy volunteers were enrolled. Each participant underwent two evaluations, at a 7-day interval. Ten minutes before the main meal, the baseline area of gastric volume was determined by ultrasonography. The subject was then given one Prodigest® or placebo capsule and, then consumed a standardized meal. One hour after the meal, the gastric volume was measured again. Two weeks after the second evaluation, three subjects repeated the above-mentioned procedures taking two capsules of Prodigest®. RESULTS: The mean gastric area at baseline was 3.2±0.5 cm2; after the meal, this figure was 8.4±0.7 cm2 with Prodigest® and 11.0±1.5 cm2 with placebo (p<0.001). The after-meal gastric area was significantly smaller, with a -24% difference, following the combination of extracts, as compared with placebo (p<0.001). The effect of two capsules of Prodigest® seems to be more evident but due to the very small number of the patients sample further clinical data are necessary before confirming the dose-related effects. CONCLUSIONS: This pilot study shows that Prodigest®, a standardized extract of ginger and artichoke, significantly promotes gastric emptying in healthy volunteers without being associated with notable adverse effects. [ABSTRACT FROM AUTHOR]

Published
2016

71. New tetracyclic colchicinoids from the reaction of N-deacetylthiocolchicine and N-deacetylcolchicine with nitrous acid and tert-butyl nitrite

Author

Danieli, B, Lesma, G, Passarella, D, Prosperi, D, Sacchetti, A, Silvani, A, Destro, R, May, E, Bombardelli, E, Danieli, B, Lesma, G, Passarella, D, Prosperi, D, Sacchetti, A, Silvani, A, Destro, R, May, E, and Bombardelli, E

Abstract

Reaction of N-deacetylthiocolchicine (3) and N-deacetylcolchicine (4) with nitrous acid (HONO) furnished the new tetracyclic colchicinoids 5 and 6, as well as the Demyanov-rearrangement products 7 and 8. Starting from 3, the pyrazole-containing tetracycle 9 was obtained. The novel compounds were characterized spectroscopically, and an X-ray crystal-structure analysis of 5 allowed us to establish the absolute configurations at the stereogenic centers

Published
2003

86. Can nausea and vomiting be treated with ginger extract?

Author

GIACOSA, A., MORAZZONI, P., BOMBARDELLI, E., RIVA, A., BIANCHI PORRO, G., and RONDANELLI, M.

Abstract

Ginger (Zingiber officinale) is a spice traditionally used to treat indigestion, nausea and vomiting. Ginger extracts accelerate gastric emptying and stimulate gastric antral contractions. These effects are mainly due to the presence of gingerols and shogaols and their activity on cholinergic M receptors and serotonergic 5-HT and 5-HT receptors. Various researches on this subject have led to controversial results, due to the chemical instability of ginger extracts and particularly of gingerols, which are readily-oxidizable substances. A systematic review of double-blind, placebo-controlled, randomized studies highlighted the potential efficacy of ginger on the prevention and treatment of nausea and vomiting of various origins, even though additional controlled studies are needed. This review focuses on pregnancy-induced nausea and vomiting and on chemotherapy induced nausea, and hypothesizes a therapeutic role for ginger extracts in case of side effects, as an alternative to traditional prokinetic drugs such as domperidone, levosulpiride or metoclopramide. [ABSTRACT FROM AUTHOR]

Published
2015

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