Effect of ricinoleic acid in acute and subchronic experimental models of inflammation.

Observational studies indicate that topical application of ricinoleic acid (RA), the main component of castor oil, exerts remarkable analgesic and anti-inflammatory effects. Pharmacological characterization has shown similarities between the effects of RA and those of capsaicin, suggesting a potential interaction of this drug on sensory neuropeptide-mediated neurogenic inflammation. The aim of this study was to assess RA anti-inflammatory activities in comparison with capsaicin in several models of acute and subchronic inflammation. The acute inflammation was induced by intradermal injection of carrageenan in the mouse or by histamine in the guinea-pig eyelid. In either experiment, the extent of the oedema thickness was measured. Subchronic oedema was induced by complete Freund's adjuvant injection in the ventral right paw of mice. Tissue substance P (SP) was measured in the carrageenan experiments by radioimmunoassay (RIA). It was found that the acute topical application of RA (0.9 mg/mouse) or capsaicin (0.09 mg/mouse) significantly increased the mouse paw oedema induced by carrageenan, while an 8-day repeated topical treatment with the same doses of both compounds resulted in a marked inhibition of carrageenan-induced paw oedema matched by a reduction in SP tissue levels. Similar effects were found against histamine-induced eyelid oedema in guinea-pigs after acute or repeated application of RA or capsaicin. RA and capsaicin given for 1-3 weeks reduced the established oedema induced by Freund's adjuvant, a subchronic model of inflammation, particularly if given by the intradermal route. Either in mouse paw or in guinea-pig eyelid, capsaicin but not RA by itself produced a slight hyperemia and activation of a behavioural response (e.g. scratching of the eyelids). On the basis of the present results, RA may be seen as a new capsaicin-like, non-pungent anti-inflammatory agent suitable for peripheral application

Autoradiographic mapping of pulmonary NK1 and NK2 tachykinin receptors and changes after repeated antigen challenge in guinea pigs

An autoradiographic technique was used to study the distribution of changes in pulmonary NK1 and NK2 receptors in guinea pig lung after repeated antigen challenge. Specific labeling of [3H] CP96345 (NK1 receptors and [3H] SR48968 (NK2 receptors) was localized over the tracheal and bronchial smooth muscle; the density of binding increased towards smaller airways with a higher density for [3H]CP96345 binding. Branchial epithelium and pulmonary blood vessels were also labeled densely with [3H] CP96345. No remarkable difference in the pattern of distribution of pulmonary NK1 and NK2 tachykinin receptors was observed between control, vehicle-challenged, and repeatedly antigen-challenged (weekly for three times) guinea pigs. A significant reduction in specific labeling of [3H] CP96345 (p < 0.01) and [3H]SR48968 (P < 0.05) over pulmonary structures was observed in antigen-challenged compared to control or vehicle-challenged animals. This study provides evidence that NK1 and NK2 tachykinin receptors are both localized to smooth muscle of all sizes in guinea pig airways and provides further evidence for a discrete distribution of NK1 and NK2 tachykinin receptors, consistent with their relative functional activities. In an established model of airway inflammation a decrease in the expression of NK1 and NK2 tachykinin receptors was evident on several different cell types within the lung, and this could influence airway and vascular reactivity.link_to_subscribed_fulltex

Isbufylline, a new xanthine derivative, inhibits airways hyperresponsiveness and airways inflammation in guinea pigs.

The pharmacological actions of the new xanthine, isbufylline, were evaluated in several models of airway hyperresponsiveness and airway inflammation in guinea pigs. At a dose (106 umol/kg i.p.) providing complete protection against acetylcholine aerosol-induced dyspnea in the guinea pig, isbufylline inhibited platelet activating factor (PAF)- and antigen-induced eosinophil infiltration into bronchoalveolar lavage fluid 24 h after challenge of normal and actively immunized guinea pigs, respectively. In addition, this dose of isbufylline also inhibited capsaicin-induced extravasation of protein into bronchoalveolar lavage fluid. Isbufylline, 4.2 umol/ kg i.v., significantly inhibited PAF-induced bronchial hyper-responsiveness to i.v. histamine, without exerting evident bronchodilator activity. On the other hand the bronchodilator, salbutamol, at a dose (10.4 umol kg i.p.) shown to be equieffective to isbufylline (106 umol/kg i.p.) for blocking acetylcholine aerosol-induced dyspnea, had no protective action against PAF- or antigen-induced eosinophil recruitment in bronchoalveolar lavage fluid, or against capsaicin-induced plasma protein extravasation. Furthermore, salbutamol (3.5 umol/kg) significantly potentiated allergen-induced cell infiltration and PAF-induced bronchial hyperresponsiveness. The results suggest that isbufylline can exert significant anti-inflammatory actions in guinea pig airways, in addition to its bronchodilator activity. These pharmacological activities are not shared by the beta2-adrenoceptor agonist, salbutamol

Cutaneous lesions in capsaicin-pretreated rats: a trophic role of capsaicin-sensitive afferents?

Skin lesions (wounds, scabs, areas of alopecia) are observed mainly in the head of most rats treated as newborns with capsaicin. No major differences were recorded between capsaicin-or vehicle-treated animals in spontaneous or novelty-induced grooming. Both SP-LI and TK-LI in various skin areas were significantly reduced by systemic capsaicin pretreatment. Fur regrowth was reduced and skin ulcers increased in caspaicin-pretreated rats. All these findings indicate that capsaicin-sensitve nerves play a trophic role in the rat skin. The restricted localization of skin lesions apparently results from 'normal' injurious factors (such grooming) on a distrophic skin

Properties of slowly rotating asteroids from the Convex Inversion Thermophysical Model

Context. Recent results for asteroid rotation periods from the TESS mission showed how strongly previous studies have underestimated the number of slow rotators, revealing the importance of studying those targets. For most slowly rotating asteroids (those with P > 12 h), no spin and shape model is available because of observation selection effects. This hampers determination of their thermal parameters and accurate sizes. Also, it is still unclear whether signatures of different surface material properties can be seen in thermal inertia determined from mid-infrared thermal flux fitting. Aims. We continue our campaign in minimising selection effects among main belt asteroids. Our targets are slow rotators with low light-curve amplitudes. Our goal is to provide their scaled spin and shape models together with thermal inertia, albedo, and surface roughness to complete the statistics. Methods. Rich multi-apparition datasets of dense light curves are supplemented with data from Kepler and TESS spacecrafts. In addition to data in the visible range, we also use thermal data from infrared space observatories (mainly IRAS, Akari and WISE) in a combined optimisation process using the Convex Inversion Thermophysical Model. This novel method has so far been applied to only a few targets, and therefore in this work we further validate the method itself. Results. We present the models of 16 slow rotators, including two updated models. All provide good fits to both thermal and visible data.The obtained sizes are on average accurate at the 5% precision level, with diameters found to be in the range from 25 to 145 km. The rotation periods of our targets range from 11 to 59 h, and the thermal inertia covers a wide range of values, from 2 to −2 s−1∕2 K−1, not showing any correlation with the period. Conclusions. With this work we increase the sample of slow rotators with reliable spin and shape models and known thermal inertia by 40%. The thermal inertia values of our sample do not display a previously suggested increasing trend with rotation period, which might be due to their small skin depth