Detection, characterization, and persistence of Campylobacter hepaticus, the cause of spotty liver disease in layer hens.

A Campylobacter species was first described as the etiological agent of Spotty Liver Disease (SLD) in 2015 and subsequently named as Campylobacter hepaticus in 2016. The bacterium predominantly affects barn and/or free-range hens at peak lay, is fastidious and difficult to isolate, which has impeded elucidation of its sources, means of persistence and transmission. Ten farms from South-Eastern Australia, of which 7 were free range entities participated in the study. A total of 1,404 specimens from layers and 201 from environmental sources, were examined for the presence of C. hepaticus. In this study, our principal findings included the continuing detection of C. hepaticus infection in a flock following an outbreak, indicating a possible transition of infected hens to asymptomatic carriers, that was also characterized by no further occurrence of SLD in the flock. We also report that the first outbreaks of SLD on newly commissioned free-range farms affected layers ranging from 23 to 74 wk of age, while subsequent outbreaks in replacement flocks on these farms occurred during the more conventional peak lay period (23-32 wk of age). Finally, we report that in the on-farm environment, C. hepaticus DNA was detected in layer feces, inert elements such as stormwater, mud, soil, as well as in fauna such as flies, red mites, Darkling beetles, and rats. While in off-farm locations, the bacterium was detected in feces from a variety of wild birds and a canine.

Rheumatic heart disease: A review of the current status of global research activity.

Rheumatic heart disease (RHD) is a serious and long-term consequence of acute rheumatic fever (ARF), an autoimmune sequela of a mucosal infection by Streptococcus pyogenes (Group A Streptococcus, Strep A). The pathogenesis of ARF and RHD is complex and not fully understood but involves host and bacterial factors, molecular mimicry, and aberrant host innate and adaptive immune responses that result in loss of self-tolerance and subsequent cross-reactivity with host tissues. RHD is entirely preventable yet claims an estimated 320 000 lives annually. The major burden of disease is carried by developing nations and Indigenous populations within developed nations, including Australia. This review will focus on the epidemiology, pathogenesis and treatment of ARF and RHD in Australia, where: streptococcal pyoderma, rather than streptococcal pharyngitis, and Group C and Group G Streptococcus, have been implicated as antecedents to ARF; the rates of RHD in remote Indigenous communities are persistently among the highest in the world; government register-based programs coordinate disease screening and delivery of prophylaxis with variable success; and researchers are making significant progress in the development of a broad-spectrum vaccine against Strep A.

Correlation between Fatty Acid Profile and Anti-Inflammatory Activity in Common Australian Seafood by-Products.

Marine organisms are a rich source of biologically active lipids with anti-inflammatory activities. These lipids may be enriched in visceral organs that are waste products from common seafood. Gas chromatography-mass spectrometry and fatty acid methyl ester (FAME) analyses were performed to compare the fatty acid compositions of lipid extracts from some common seafood organisms, including octopus (Octopus tetricus), squid (Sepioteuthis australis), Australian sardine (Sardinops sagax), salmon (Salmo salar) and school prawns (Penaeus plebejus). The lipid extracts were tested for anti-inflammatory activity by assessing their inhibition of nitric oxide (NO) and tumor necrosis factor alpha (TNFα) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse cells. The lipid extract from both the flesh and waste tissue all contained high amounts of polyunsaturated fatty acids (PUFAs) and significantly inhibited NO and TNFα production. Lipid extracts from the cephalopod mollusks S. australis and O. tetricus demonstrated the highest total PUFA content, the highest level of omega 3 (ω-3) PUFAs, and the highest anti-inflammatory activity. However, multivariate analysis indicates the complex mixture of saturated, monounsaturated, and polyunsaturated fatty acids may all influence the anti-inflammatory activity of marine lipid extracts. This study confirms that discarded parts of commonly consumed seafood species provide promising sources for the development of new potential anti-inflammatory nutraceuticals.

Review of anti-inflammatory, immune-modulatory and wound healing properties of molluscs.

ETHNOPHARMACOLOGICAL RELEVANCE: This review focuses on traditional and contemporary anti-inflammatory uses of mollusc-derived products summarising all the in vitro, in vivo and human clinical trials that have tested the anti-inflammatory activity of molluscan natural products. Inflammatory conditions, burns and wounds have been an ongoing concern for human health since the early era of civilisation. Many texts from ancient medicine have recorded the symptoms, signs and treatments for these conditions. Natural treatments are well-documented in traditional European medicine, Traditional Chinese Medicine (TCM), Siddha and ancient Mediterranean and African traditional medicine and include a surprisingly large number of molluscan species. MATERIALS AND METHODS: An extensive review of the Materia Medica and scientific literature was undertaken using key word searches for "mollusc" and "anti-inflammatory" or "immunomodulatory" or "wound healing". RESULTS: Molluscs have been used in ethnomedicine by many traditional cultures to treat different aspects of inflammatory conditions. We found 104 different anti-inflammatory preparations from a variety of molluscan species, of which 70 were from the well-documented Traditional Chinese Medicine (TCM). This traditional use of molluscs has driven the testing for inflammatory activity in extracts from some species in the phylum Mollusca, with 20 in vitro studies, 40 in vivo animal studies and 14 human clinical trials performed to substantiate the anti-inflammatory and wound healing activity of molluscs. Some of these studies have led to the approval of mollusc-derived products to be used as over-the-counter (OTC) nutraceuticals, like Lyprinol® and Biolane™ from the New Zealand green lipped mussel Perna canaliculus. CONCLUSION: Natural products provide important leads for the development of pharmaceuticals, including anti-inflammatory agents. Only a small proportion of the molluscan traditional medicines have been tested to confirm their anti-inflammatory activity and most screening studies have tested crude extracts from molluscs without any chemical characterisation. This highlights the need for further research to strategically identify the anti-inflammatory compounds in molluscan medicines to provide leads for novel anti-inflammatory drugs in the future.

Brominated indoles from a marine mollusc inhibit inflammation in a murine model of acute lung injury.

New drug leads for the treatment of inflammation are urgently needed. Marine molluscs are widely used as traditional medicines for the treatment of inflammation. Here we report the positive effects of a hypobranchial gland (HBG) extract and the dominant bioactive compound 6-bromoisatin from the Muricidae mollusc Dicathais orbita, for reducing lipopolysaccharide (LPS) induced acute lung inflammation in a mouse model. Both 6-bromoisatin and the HBG extract suppressed the inflammatory response in mice that were pre-treated by oral gavage at 48, 24 and 1 h prior to LPS infusion. The inflammatory antagonists were tested at concentrations of 0.5 mg/g and 0.1 mg/g HBG extract and 0.1 mg/g and 0.05 mg/g 6-bromoisatin in carrier oil and all treatments reduced inflammation as indicated by a significant suppression of inflammatory markers present in bronchoalveolar lavage fluid (BALF), in comparison to LPS induced positive control mice administered the carrier oil alone (p < 0.0001). Tumour necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1ß) levels, in addition to total protein concentration were all significantly reduced in BALF from mice treated with the extract or 6-bromoisatin. Furthermore, all treatment groups showed significant reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the positive control (p < 0.0001). The combined results from this study and our previous in vitro studies indicate that 6-bromoisatin in the HGB extracts inhibit the activation of inflammatory signalling pathway. The results from this study further confirm that the HBG extract from Muricidae molluscs and 6-bromoisatin are bioavailable and effective in vivo, thus have potential for development as natural therapeutic agents for inflammation.

Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine Mollusc.

Marine molluscs are rich in biologically active natural products that provide new potential sources of anti-inflammatory agents. Here we used bioassay guided fractionation of extracts from the muricid Dicathais orbita to identify brominated indoles with anti-inflammatory activity, based on the inhibition of nitric oxide (NO) and tumour necrosis factor α (TNFα) in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and prostaglandin E2 (PGE2) in calcium ionophore-stimulated 3T3 ccl-92 fibroblasts. Muricid brominated indoles were then compared to a range of synthetic indoles to determine structure-activity relationships. Both hypobranchial gland and egg extracts inhibited the production of NO significantly with IC50 of 30.8 and 40 µg/mL, respectively. The hypobranchial gland extract also inhibited the production of TNFα and PGE2 with IC50 of 43.03 µg/mL and 34.24 µg/mL, respectively. The purified mono-brominated indole and isatin compounds showed significant inhibitory activity against NO, TNFα, and PGE2, and were more active than dimer indoles and non-brominated isatin. The position of the bromine atom on the isatin benzene ring significantly affected the activity, with 5Br > 6Br > 7Br. The mode of action for the active hypobranchial gland extract, 6-bromoindole, and 6-bromoisatin was further tested by the assessment of the translocation of nuclear factor kappa B (NFκB) in LPS-stimulated RAW264.7 mouse macrophage. The extract (40 µg/mL) significantly inhibited the translocation of NFκB in the LPS-stimulated RAW264.7 macrophages by 48.2%, whereas 40 µg/mL of 6-bromoindole and 6-bromoistain caused a 60.7% and 63.7% reduction in NFκB, respectively. These results identify simple brominated indoles as useful anti-inflammatory drug leads and support the development of extracts from the Australian muricid D. orbita, as a new potential natural remedy for the treatment of inflammation.