Efficacy and safety of a non-mineral oil adjuvanted injectable vaccine for the protection of Atlantic salmon (Salmo salar L.) against Flavobacterium psychrophilum.

Flavobacterium psychrophilum is the causative agent of Rainbow Trout Fry Syndrome which has had a major impact on global salmonid aquaculture. Recent outbreaks in Atlantic salmon in Scotland and Chile have added to the need for a vaccine to protect both salmon and trout. At present no licensed vaccines are available in Europe, leaving antibiotics as the only course of action to contain disease outbreaks. Outbreaks generally occur in fry at temperatures between 10 and 15 °C. Recently outbreaks in larger fish have given added impetus to the development of a vaccine which can provide long term protection from this highly heterogeneous pathogen. Most fish injectable vaccines are formulated with oil emulsion adjuvants to induce strong and long lasting immunity, but which are known to cause side effects. Alternative adjuvants are currently sought to minimise these adverse effects. The current study was performed to assess the efficacy of a polyvalent, whole cell vaccine containing formalin-inactivated F. psychrophilum to induce protective immunity in Atlantic salmon. The vaccine was formulated with an adjuvant containing squalene and aluminium hydroxide, and was compared to a vaccine formulated with a traditional oil adjuvant, Montanide ISA 760VG, and a non-adjuvanted vaccine. Duplicate groups of salmon (23.5 ± 6.8 g) were vaccinated with each of the vaccine formulations or phosphate buffered saline by intraperitoneal injection. Fish were challenged by intramuscular injection with F. psychrophilum six weeks post-vaccination to test the efficacy of the vaccines. Cumulative mortality reached 70% in the control salmon, while the groups of salmon that received vaccine had significantly lower mortality than the controls (p = 0.0001), with no significant difference in survival between vaccinated groups. The squalene/alum adjuvant was safe, more readily metabolised by the fish and induced less histopathological changes than the traditional oil adjuvant.

Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice.

BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives. METHODS: To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I(CAP))- and heat (I(heat))-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain. RESULTS: I(CAP) (P<0.01) and I(heat) (P<0.05) of TRPV1 were significantly blocked by 10 µM KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05). CONCLUSIONS: KMS4034 may be an effective analgesic for various pain conditions.

Curcumin produces an antihyperalgesic effect via antagonism of TRPV1.

Curcumin has diverse therapeutic effects, such as anti-inflammatory, anti-oxidant, anti-cancer, and antimicrobial activities. The vanilloid moiety of curcumin is considered important for activation of the transient receptor potential vanilloid 1 (TRPV1), which plays an important role in nociception. However, very little is known about the effects of curcumin on nociception. In the present study, we investigated whether the anti-nociceptive effects of curcumin are mediated via TRPV1 by using nociceptive behavioral studies and in vitro whole-cell patch-clamp recordings in the trigeminal system. Subcutaneous injection of capsaicin in the vibrissa pad area of rats induced thermal hyperalgesia. Intraperitoneally administered curcumin blocked capsaicin-induced thermal hyperalgesia in a dose-dependent manner. Whereas curcumin reduced capsaicin-induced currents in a dose-dependent manner in both trigeminal ganglion neurons and TRPV1-expressing HEK 293 cells, curcumin did not affect heat-induced TRPV1 currents. Taken together, our results indicate that curcumin blocks capsaicin-induced TRPV1 activation and thereby inhibits TRPV1-mediated pain hypersensitivity.

Production of eleutherosides in in vitro regenerated embryos and plantlets of Eleutherococcus chiisanensis.

High frequency somatic embryogenesis of Eleutheorcoccus chiisanensis was achieved through suspension culture of embryogenic cells in hormone-free Murashige and Skoog liquid medium supplemented with 30 g sucrose l-1. Cotyledonary somatic embryos were germinated and converted into plantlets using 20 microM: gibberellic acid which were then grown in a 10 l airlift bioreactor. HPLC analysis revealed the accumulation of eleutheroside B, E and E1 in the embryos and plantlets. Thus mass production of embryos and plantlets of E. chiisanensis can be achieved in liquid cultures and the biomass produced may become an alternative source of eleutherosides.