Myrtenol is a bicyclic monoterpene with anti-inflammatory properties. However, the mechanisms involved are partially unknown. Here, we investigated the effect of myrtenol during experimental chronic arthritis and the possible modulating activity of oxidative stress and neutrophil migration. Complete Freund's Adjuvant (CFA)-sensitized rats were treated with vehicle (1 mL/kg, po), myrtenol (12.5, 25 or 50 mg/kg, po), indomethacin (10 mg/kg, po) or dexamethasone (0.4 mg/kg) followed by intra-articular injection of CFA (0.5 mg/mL, 50 μL per joint). Then, paw edema and articular incapacitation (paw elevation time) were evaluated for 14 days. On the last day, a blood concentration superoxide dismutase (SOD) and nitrite was determined. In another experimental setting, human neutrophils were incubated with vehicle (sterile saline, 1 mL) or myrtenol (10-100 ng/mL) and the in vitro chemotaxis to N-formylmethionine-leucyl-phenylalanine (fMLP) (10 M/well) was evaluated. In addition, antiinflammatory effect of myrtenol was investigated in carrageenan-induced peritonitis. We found that CFA induced a prominent paw swelling and incapacitation of the joint, which were significantly prevented by myrtenol (P < 0.05). In addition, blood accumulation nitrite was attenuated by myrtenol when compared with vehicle-treated CFA group (P < 0.05). Furthermore, plasma levels of SOD were significantly increased by myrtenol versus vehicle-treated CFA group (P < 0.05). Moreover, fMLP-triggered neutrophil chemotaxis and carrageenan-induced peritonitis were markedly prevented by myrtenol (P < 0.05). Therefore, myrtenol showed anti-inflammatory and antinociceptive effects on experimental chronic arthritis, which seems to be related to the direct modulation of neutrophil migration and antioxidant activity.

These results suggest that α-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization.

Inflammation is characterized by vasodilatation, increase of blood flow and vascular permeability, migration of leucocytes to the inflammatory site, and production of cytokines. The aim of this study was evaluate the anti‐inflammatory and antinociceptive effects of (−)‐myrtenol, a plant‐derived monoterpene alcohol, in mice and its possible mechanisms. Myrtenol was used in classical models of inflammation (paw oedema induced by different agents, carrageenan‐induced peritonitis, myeloperoxidase levels and cytokine measurement) and nociception (acetic acid‐induced writhing, hot‐plate test, and paw licking induced by formalin, glutamate, and capsaicin). Pretreatment with myrtenol effectively inhibited paw oedema induced by carrageenan, compound 48/80, histamine, serotonin and prostaglandin E2. Myrtenol also reduced the cell counts, myeloperoxidase activity and cytokine levels (interleukin 1β, but not tumour necrosis factor‐α) of the peritoneal cavity induced by carrageenan. In addition, myrtenol inhibited acetic acid‐induced writhing, did not significantly prolong the latency time in the hot‐plate test, decreased licking time caused by an intraplantar injection of formalin (only in the second phase), glutamate and capsaicin. Myrtenol reduces the inflammatory response and nociception in mice due to the inhibition of the release of inflammatory mediators, cell migration and also to the signalling pathway of receptors involved in the transmission of pain. Copyright © 2014 John Wiley & Sons, Ltd.

The aim of this study was to determine the current practices of established general practitioners in managing patients with drug and alcohol-related problems and identify gaps in training. A random sample of general practitioners completed a survey assessing diagnostic skills and referral practices concerning alcohol and illicit drug use in general practices in February 1999, comprising 110 general practitioners registered with the Central Sydney Division of General Practice. The main outcome measures were competent skills and knowledge, willingness to treat. The majority (96%) of GPs provided clinically appropriate responses for at least one drug category, although none received this rating for all six. Most general practitioners reported that they were unwilling to treat heroin and cocaine problems themselves but expressed willingness to refer patients appropriately. More than a quarter of general practitioners were unaware of the safe drinking levels for men and women or the appropriate treatment for patients consuming above such levels. Age, years in practice, type of practice, willingness to obtain drug use histories and post-graduate training were all significantly associated with general practitioners' willingness to treat and competence in managing drug and alcohol-related problems. In this study, general practioners reported low levels of skills and referrals for treatment of illicit drug use and suboptimal skills in the management of alcohol problems. The results suggest that a more comprehensive approach to education and training is required to bring about a change in practice behaviour. [Fucito LM, Gomes BS, Murnion B, Haber PS. General practitioners' diagnostic skills and referral practices in managing patients with drug and alcohol-related health problems: implications for medical training and education programmes.