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Fewer guinea-pigs
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News & Comment
micturition contractions was not different in the two experimental groups. A similar urodynamic profile was detected when transurethral cystometries were performed in P2rx3−/− anesthetized mice. P2X3 receptors could be the crucial link for conferring mechanosensitivity to bladder capsaicin-sensitive neurons These urodynamic changes – increased bladder capacity without gross anatomical modifications and no sign of impairment of the motor function of the viscus – largely mimic those produced by the systemic administration of capsaicin in adult animals and suggest a selective impairment of bladder sensory function in P2rx3−/− mice. Thus, the findings of Cockayne et al. raise the question of whether P2rx3−/− receptors could be the crucial link for conferring
TRENDS in Pharmacological Sciences Vol. 22 No.1 January 2001
mechanosensitivity to bladder capsaicinsensitive neurons. Taking into account the physiological versus the pathophysiological relevance of these findings, caution should be expressed, considering that the urodynamic assessment performed through invasive methods (surgically implanted catheters) cannot be exactly representative of the normal micturition reflex, because the surgical manipulation of the viscus could have induced a mild bladder hyperactivity. This manipulation could sensitize or recruit C-fibers, which are not normally engaged in the micturition reflex, thus disclosing an effect of drugs and mediators that modulate the activity of capsaicin-sensitive nociceptors. In this respect, the hypoalgesia exhibited by either capsaicin-pretreated or P2rx3−/− mice on both phases of the formalin test (see also Ref. 2) could indicate that ATP is an
important chemical activator of capsaicin-sensitive neurons following tissue injury at the peripheral level. Therefore, the development of noninvasive techniques to measure bladder function should rule out the possibility that tissue injury caused by surgical procedures might be responsible for an involvement of capsaicin-sensitive nerves in ATP-mediated bladder mechanosensitivity to distension. 1 Cockayne, D.A. et al. (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407, 1011–1015 2 Souslova, V. et al. (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407, 1015–1017
Alessandro Lecci [email protected]
In Brief
Antidepressant chromium
Victorious Viagra
Chromium supplements are a cheap and remarkably effective treatment for depression, according to a study published in the December issue of The International Journal of Neuropsychopharmacology. Eight patients suffering from a range of depressive disorders reported rapid improvements upon taking chromium picolinate, with very few minor side-effects (vivid dreaming, mild headache and a caffeine-like increase in alertness). Chromium, a trace element, has welldescribed effects on carbohydrate metabolism and insulin utilization, and studies have recently shown that it can be helpful in treating diabetes and the mood disturbances that accompany premenstrual syndrome. The link to depression was established by Malcolm McLeod (University of North Carolina, Chapel Hill, NC, USA) when a patient reported relief from his depression after taking a vitamin–mineral–herbal preparation. Chromium, in its very different hexavalent form, has recently had a bad press as the toxic culprit in the movie Erin Brockovich. Those advocating chromium picolinate as a dietary supplement might find themselves battling skepticism at all levels, from movie-goers to the producers of Prozac. AS
Scientists at the Pfizer European Research Centre (Sandwich, UK) have secured the Prix Galien award following the discovery and development of Viagra, a drug that is expected to improve the quality of life of more than 100 million men who suffer from erectile dysfunction (ED). By relaxing blood vessels, this phosphodiesterase 5 inhibitor increases blood flow to the penis during sexual stimulation, replacing previous treatments for ED such as penile injections, surgery and the use of vacuum devices. Since 1970, the Prix Galien award has been presented by an international jury of medical researchers to scientists whose innovative discoveries are expected to have long-term, positive impacts on patient care. As such, this prize is viewed as the highest accolade for biomedical research and development industries. For a fuller discussion of the physiology of erectile dysfunction and the mode of action of Viagra, see the review by Kadowitz and colleagues in last month’s issue of TiPS [Bivalcqua, T.J. et al. (2000) Pharmacotherapy for erectile dysfunction. Trends Pharmacol. Sci. 21, 484–489]. EK
Fewer guinea-pigs A new skin sensitization test for experimental animals, the murine local lymph node assay (LLNA), has won the SmithKline Beecham Laboratory Animal Welfare Prize (2000) for its originators Ian Kimber (Syngenta), Frank Gerberick (Procter & Gamble) and David Basketter (Unilever). The LLNA test obviates the need for the injection of test materials and circumvents the elicitation of allergic reactions, which accompany standard guinea-pig testing. The Research Defence Society, a UK-based organization that awards the prize annually, believes that the introduction of LLNA testing will reduce the number of animals being used for skin allergy testing in the future. AS
http://tips.trends.com 0165-6147/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:
This month’s ‘In Brief’ articles were written by Emma Knight and Adam Smith
News & Comment
micturition contractions was not different in the two experimental groups. A similar urodynamic profile was detected when transurethral cystometries were performed in P2rx3−/− anesthetized mice. P2X3 receptors could be the crucial link for conferring mechanosensitivity to bladder capsaicin-sensitive neurons These urodynamic changes – increased bladder capacity without gross anatomical modifications and no sign of impairment of the motor function of the viscus – largely mimic those produced by the systemic administration of capsaicin in adult animals and suggest a selective impairment of bladder sensory function in P2rx3−/− mice. Thus, the findings of Cockayne et al. raise the question of whether P2rx3−/− receptors could be the crucial link for conferring
TRENDS in Pharmacological Sciences Vol. 22 No.1 January 2001
mechanosensitivity to bladder capsaicinsensitive neurons. Taking into account the physiological versus the pathophysiological relevance of these findings, caution should be expressed, considering that the urodynamic assessment performed through invasive methods (surgically implanted catheters) cannot be exactly representative of the normal micturition reflex, because the surgical manipulation of the viscus could have induced a mild bladder hyperactivity. This manipulation could sensitize or recruit C-fibers, which are not normally engaged in the micturition reflex, thus disclosing an effect of drugs and mediators that modulate the activity of capsaicin-sensitive nociceptors. In this respect, the hypoalgesia exhibited by either capsaicin-pretreated or P2rx3−/− mice on both phases of the formalin test (see also Ref. 2) could indicate that ATP is an
important chemical activator of capsaicin-sensitive neurons following tissue injury at the peripheral level. Therefore, the development of noninvasive techniques to measure bladder function should rule out the possibility that tissue injury caused by surgical procedures might be responsible for an involvement of capsaicin-sensitive nerves in ATP-mediated bladder mechanosensitivity to distension. 1 Cockayne, D.A. et al. (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407, 1011–1015 2 Souslova, V. et al. (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407, 1015–1017
Alessandro Lecci [email protected]
In Brief
Antidepressant chromium
Victorious Viagra
Chromium supplements are a cheap and remarkably effective treatment for depression, according to a study published in the December issue of The International Journal of Neuropsychopharmacology. Eight patients suffering from a range of depressive disorders reported rapid improvements upon taking chromium picolinate, with very few minor side-effects (vivid dreaming, mild headache and a caffeine-like increase in alertness). Chromium, a trace element, has welldescribed effects on carbohydrate metabolism and insulin utilization, and studies have recently shown that it can be helpful in treating diabetes and the mood disturbances that accompany premenstrual syndrome. The link to depression was established by Malcolm McLeod (University of North Carolina, Chapel Hill, NC, USA) when a patient reported relief from his depression after taking a vitamin–mineral–herbal preparation. Chromium, in its very different hexavalent form, has recently had a bad press as the toxic culprit in the movie Erin Brockovich. Those advocating chromium picolinate as a dietary supplement might find themselves battling skepticism at all levels, from movie-goers to the producers of Prozac. AS
Scientists at the Pfizer European Research Centre (Sandwich, UK) have secured the Prix Galien award following the discovery and development of Viagra, a drug that is expected to improve the quality of life of more than 100 million men who suffer from erectile dysfunction (ED). By relaxing blood vessels, this phosphodiesterase 5 inhibitor increases blood flow to the penis during sexual stimulation, replacing previous treatments for ED such as penile injections, surgery and the use of vacuum devices. Since 1970, the Prix Galien award has been presented by an international jury of medical researchers to scientists whose innovative discoveries are expected to have long-term, positive impacts on patient care. As such, this prize is viewed as the highest accolade for biomedical research and development industries. For a fuller discussion of the physiology of erectile dysfunction and the mode of action of Viagra, see the review by Kadowitz and colleagues in last month’s issue of TiPS [Bivalcqua, T.J. et al. (2000) Pharmacotherapy for erectile dysfunction. Trends Pharmacol. Sci. 21, 484–489]. EK
Fewer guinea-pigs A new skin sensitization test for experimental animals, the murine local lymph node assay (LLNA), has won the SmithKline Beecham Laboratory Animal Welfare Prize (2000) for its originators Ian Kimber (Syngenta), Frank Gerberick (Procter & Gamble) and David Basketter (Unilever). The LLNA test obviates the need for the injection of test materials and circumvents the elicitation of allergic reactions, which accompany standard guinea-pig testing. The Research Defence Society, a UK-based organization that awards the prize annually, believes that the introduction of LLNA testing will reduce the number of animals being used for skin allergy testing in the future. AS
http://tips.trends.com 0165-6147/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:
This month’s ‘In Brief’ articles were written by Emma Knight and Adam Smith