CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-ß-producing macrophages and T cells.

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-ß via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-ß)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

Identification of microsatellite markers in coffee associated with resistance to Meloidogyne exigua.

Meloidogyne species are destructive phytonematodes that result in reduced yields of coffee. The classic test for resistance to Meloidogyne exigua in coffee progenies is both expensive and time-consuming. The use of molecular marker techniques can assist the selection process when it is difficult to measure the phenotype, such as in cases of resistance to nematode infestation. The objective of this study was to identify microsatellite markers associated with resistance to M. exigua in F5 progenies of coffee derived from a cross between Híbrido de Timor 440-10 and Catuaí Amarelo IAC 86. Of the 44 simple sequence repeat (SSR) markers evaluated, 11 showed a polymorphic pattern with a mean number of 4.5 alleles per marker. Clustering analysis classified 82 progenies into three groups related to the response to nematodes and parental genotypes allocated to different groups (resistant and susceptible). SSRCafé 40 allele 2, SSRCafé 15 allele 3, SSRCafé 20 allele 3, and SSRCafé 13 allele 1 were negatively correlated with reproduction factor. In addition, SSRCafé 13 allele 2, SSRCafé 19 allele 3, SSRCafé 40 allele 2, SSRCafé 15 allele 3, and SSRCafé 20 allele 3 were correlated with the root gall index of M. exigua. These SSR markers, which have been validated in this population, represent a potential method to select progenies resistant to nematodes in coffee-breeding programs.

Endogenous opioid and cannabinoid mechanisms are involved in the analgesic effects of celecoxib in the central nervous system.

BACKGROUND/AIMS: In this study we analyzed the mechanisms underlying celecoxib-induced analgesia in a model of inflammatory pain in rats, using the intracerebroventricular (i.c.v.) administration of selective opioid and cannabinoid antagonists. METHODS AND RESULTS: Analgesic effects of celecoxib were prevented by selective µ-(ß-funaltrexamine) and δ-(naltrindole), but not κ-(nor-binaltorphimine) opioid antagonists, given i.c.v. 30 min before celecoxib. Similar pretreatment with AM 251, but not SR 144528, cannabinoid CB(1) and CB(2) receptor antagonists, respectively, prevented celecoxib-induced analgesia. The fatty acid amide hydrolase inhibitor, URB 597, also prevented celecoxib-induced analgesia. CONCLUSIONS: Our data provided further evidence for the involvement of endogenous opioids and revealed a new cannabinoid component of the mechanism(s) underlying celecoxib-induced analgesia.

Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain.

BACKGROUND AND PURPOSE: The analgesics, paracetamol and dipyrone are weak inhibitors of the cyclooxygenase isoforms 1 or 2 (COX-1, COX-2) but more potent on COX-3. Both are also weak anti-inflammatory agents, relative to their analgesic and antipyretic activities. In a model of inflammatory pain mediated by prostaglandins, both compounds were analgesic. We have analysed this shared effect further in order to elucidate the underlying mechanisms. EXPERIMENTAL APPROACH: Inflammation was induced in one hind paw of rats by intraplantar injection of 250 microg lambda-carrageenan (CG) and the contralateral paw injected with saline. Nociceptive thresholds to mechanical stimulation were measured immediately before and for 6 h after, injection of CG. The analgesics were s.c. or locally (intraplantar) injected either 30 min before or 2 h after CG. In some groups, naltrexone was injected (s.c. or intraplantar), 1 h before CG. KEY RESULTS: Pretreatment with paracetamol or dipyrone (60-360 mg kg(-1)) reversed hyperalgesia induced by CG and increased nociceptive threshold in the inflamed paw above the basal level (hypoalgesia). Paracetamol, but not dipyrone, also raised nociceptive thresholds in the non-inflamed paw. Subcutaneous, but not local, administration of naltrexone, a specific opioid antagonist, reversed the hypoalgesia induced by paracetamol, but similar naltrexone treatment had no effect on dipyrone-induced analgesia. CONCLUSIONS AND IMPLICATIONS: Although both paracetamol and dipyrone are inhibitors of COX isoforms and thus of prostaglandin biosynthesis and were analgesic in our model, their analgesic actions were functionally and mechanistically different. Satisfactory mechanisms of action for these analgesics still remain to be established.