Antinociceptive activity of 3ß-6ß-16ß-trihydroxylup-20 (29)-ene triterpene isolated from Combretum leprosum leaves in adult zebrafish (Danio rerio).

Drugs used to treat pain are associated with adverse effects, increasing the search for new drugs as an alternative treatment for pain. Therefore, we evaluated the antinociceptive behavior and possible neuromodulation mechanisms of triterpene 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene (CLF-1) isolated from Combretum leprosum leaves in zebrafish. Zebrafish (n = 6/group) were pretreated with CLF-1 (0.1 or 0.3 or 1.0 mg/mL; i.p.) and underwent nociception behavior tests. The antinociceptive effect of CFL-1 was tested for modulation by opioid (naloxone), nitrergic (L-NAME), nitric oxide and guanylate cyclase synthesis inhibitor (methylene blue), NMDA (Ketamine), TRPV1 (ruthenium red), TRPA1 (camphor), or ASIC (amiloride) antagonists. The corneal antinociceptive effect of CFL-1 was tested for modulation by TRPV1 (capsazepine). The effect of CFL-1 on zebrafish locomotor behavior was evaluated with the open field test. The acute toxicity study was conducted. CLF-1 reduced nociceptive behavior and corneal in zebrafish without mortalities and without altering the animals' locomotion. Thus, CFL-1 presenting pharmacological potential for the treatment of acute pain and corneal pain, and this effect is modulated by the opioids, nitrergic system, NMDA receptors and TRP and ASIC channels.

Involvement of the nitric oxide pathway in the anti-depressant-like effects of thalidomide in mice.

BACKGROUND: Thalidomide is a sedative/hypnotic agent that is currently used to treat patients suffering from multiple myeloma, myelodysplastic syndromes and erythema nodosum leprosum. Although previous studies have demonstrated that thalidomide possesses anti-depressant-like properties, the exact mechanism that thalidomide exerts this effect is not understood. In this study, we used two mouse models of depression and investigated the possible role of nitric oxide (NO), NO synthase (NOS) and inducible NOS (iNOS) in the ant-depressant-like effects of thalidomide. METHODS: Male mice were injected with different doses of thalidomide intraperitoneally. In order to assess the anti-depressant-like properties of thalidomide, the immobility time of mice was assessed in the forced swimming test (FST) and tail suspension test (TST). Locomotor activity was assessed using the open-field test. To assess the role of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME, non-specific NOS inhibitor), aminoguanidine (selective iNOS inhibitor) or L-arginine (NO precursor) were administered intraperitoneally along with specific doses of thalidomide. RESULTS: Thalidomide (10 mg/kg) significantly reduced immobility time in FST and TST. Aminoguanidine (50 mg/kg) and L-NAME (10 mg/kg) significantly augmented the anti-immobility effects of thalidomide (5 mg/kg). L-arginine (750 mg/kg) significantly inhibited the anti-immobility effects of thalidomide (10 mg/kg). None of the treatment groups demonstrated alteration of locomotor activity. CONCLUSION: Thalidomide exerts its anti-depressant-like effects through a mechanism dependent upon NO inhibition.

Effects of body temperature on righting performance of native and invasive freshwater turtles: consequences for competition.

Righting behavior of aquatic turtles might be subject to coadaptation pressures between preferred basking temperature and locomotion, given that it is mainly performed on land and may critically determine the survival of turtles. We analyzed the effect of body temperature (T(b)) on righting performance of two species of freshwater turtles, the endangered native Spanish terrapin (Mauremys leprosa), and the red-eared slider (Trachemys scripta elegans), an introduced invasive species that is displacing native turtles in the Iberian Peninsula. Interspecific differences in morphology, basking requirements and behavioral responses have been found between Spanish terrapins and introduced sliders. Therefore, we hypothesized that T(b) might differentially affect righting behavior of these two turtle species. We found a clear effect of T(b) on righting response of both M. leprosa and T. scripta, with the performance enhanced at the preferred basking temperature of each turtle species. These results suggest that righting might be coadapted to preferred basking temperature in freshwater turtles. Also, M. leprosa required longer times to right on average than T. scripta, which denotes a higher efficiency of introduced sliders at righting performance. These interspecific behavioral asymmetries in righting performance between native and exotic turtles might contribute to the greater competitive ability of introduced T. scripta, favoring the expansion of exotic sliders in the new environments in which they are introduced, in detriment to native Spanish terrapins.

Forces under the foot.

A transducer has been developed to record the shear or horizontal components of force beneath the sole of the foot. When used with a vertical force transducer it has enabled a comprehensive analysis of the mechanical forces acting beneath the foot when walking in various types of footwear. Considerable differences have been recorded between the footwear. Particularly low forces are present in a plaster cast and to a lesser extent with Plastazote insoles. The possible application of these findings to the management of ulceration of the sole of the foot in diabetes mellitus and leprosy is discussed.