Green-lipped Mussel Perna Canaliculus Research Articles

Characterization of the transcriptional effects of the plastic additive dibutyl phthalate alone and in combination with microplastic on the green-lipped mussel Perna canaliculus.

The presence and persistence of microplastics (MPs) in diverse aquatic environments are of global concern. Microplastics can impact marine organisms via direct physical interaction and the release of potentially harmful chemical additives incorporated into the plastic. These chemicals are physically bound to the plastic matrix and can leach out. The hazards associated with chemical additives to exposed organisms is not well characterized. We investigated the hazards of plastic additives leaching from plastic. We used the common plasticizer dibutyl phthalate (DBP) as a chemical additive proxy and the New Zealand green-lipped mussel (Perna canaliculus) as a model. We used early-adult P. canaliculus exposed to combinations of virgin and DBP-spiked polyvinyl chloride (PVC), MPs, and DBP alone for 7 days. Whole transcriptome sequencing (RNA-seq) was conducted to assess whether leaching of DBP from MPs poses a hazard. The differences between groups were evaluated using pairwise permutational multivariate analysis of variance (PERMANOVA), and all treatments were significantly different from controls. In addition, a significant difference was seen between DBP and PVC MP treatment. Transcriptome analysis revealed that mussels exposed to DBP alone had the most differentially expressed genes (914), followed by PVC MP + DBP (448), and PVC MP (250). Gene ontology functional analysis revealed that the most enriched pathway types were in cellular metabolism, immune response, and endocrine disruption. Microplastic treatments enriched numerous pathways related to cellular metabolism and immune response. The combined exposure of PVC MP + DBP appears to cause combined effects, suggesting that DBP is bioavailable to the exposed mussels in the PVC MP + DBP treatment. Our results support the hypothesis that chemical additives are potentially an important driver of MP toxicity. Environ Toxicol Chem 2024;00:1-11. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Paternal heat exposure affects progeny larval development in green-lipped mussels Perna canaliculus

The green-lipped mussel Perna canaliculus is critically important to the New Zealand aquaculture industry. However, the rise in marine heatwave (MHW) events poses an emerging threat to this industry through summer mortality events. This study investigated the potential for paternally mediated transgenerational plasticity to improve offspring performance under heat stress. We simulated a week-long MHW event, exposing male P. canaliculus broodstock to elevated (22°C) or ambient (17.5°C) temperatures immediately prior to spawning, and evaluated the effects of paternal heat exposure on successful development, size and acute thermal tolerance of their larvae that were also reared under ambient or elevated (20°C) temperatures through to completion of the lecithotrophic trochophore stage. Elevated paternal and larval temperatures both increased incidence of abnormal development, reducing larval yield, while initial D-veliger shell length was predominantly influenced by developmental temperature, with longer shells formed at 20°C. Veligers from heat-exposed fathers raised under 20°C showed a small, but significant, elevation in lethal tolerance 50 (LT50), the temperature at which 50% of the larvae are predicted to die, when exposed to an additional 1 h heat-shock. These results indicate that paternal heat exposure over a relatively short period can influence offspring performance in this species. The paternal exposure investigated showed limited positive effects on offspring thermal tolerance, which may be outweighed by the negative impact on larval development. As MHWs are forecasted to continue accelerating, understanding transgenerational effects of heat stress will be critical for maintaining high-quality hatchery yields through broodstock selection and may inform wild population forecasting models.

Exposure to Alexandrium spp. impairs the development of Green-lipped mussel (Perna canaliculus) embryos and larvae

The green-lipped mussel (GLM) Perna canaliculus is an economically, ecologically, and culturally important species in Aotearoa New Zealand. Since 2011, harmful algal blooms (HABs) of Alexandrium spp. have occurred annually in the Marlborough Sounds, the largest GLM aquaculture region in New Zealand. Across a similar timeframe, there has been a severe reduction in wild spat (juvenile mussel) catch. This research investigated the effects of Alexandrium pacificum (which produces paralytic shellfish toxins; PSTs) and A. minutum (a non-producer of PSTs) on the development of four GLM larval life stages (gametes, embryos, D-stage and settlement).Early life stages of GLM were exposed to environmentally relevant concentrations of Alexandrium spp. as whole cell, lysate and filtrate treatments. A 48-h exposure of embryos to whole A. pacificum cells at 500 cells mL−1 caused lysis of embryos, severe abnormalities, and reduced development through to veliger (D-stage) larvae by 85%. GLM growth was impaired at cell concentrations as low as 250 cells mL−1 during a 4-day exposure of D-stage larvae to both Alexandrium spp. Exposure of GLM to both whole and lysed treatments of Alexandrium spp. at 500 cells mL−1 resulted in halved larval growth rates (2.00 µm day−1 vs 4.48 µm day−1 in the control) and growth remained impeded during a 4-day recovery period.Both A. pacificum and A. minutum were found to negatively impact D-larvae. Both whole-cell and lysed-cell treatments of A. pacificum had similar negative effects, suggesting that Alexandrium spp. toxicity to D-larvae is independent of PSTs. Additionally, cell membrane-free treatments of A. pacificum had no negative effects on embryo development, indicating that cell surface-associated bioactive compounds may be responsible for the observed negative effects during this early life stage.Conversely, non-PST-producing A. minutum was toxic to D-stage larvae but not to embryos; larval growth was reduced following a brief 1 h exposure of sperm to cell membrane-free treatments of A. pacificum. No effects were recorded in GLM larvae exposed during settlement, highlighting the potential for differences in susceptibility of early life stages to Alexandrium spp. exposure and the influence of exposure durations.In the wild, blooms of Alexandrium spp. can persist for several months, reaching cell densities higher than those investigated in the present study, and as such may be detrimental to the vulnerable early life stages of GLM.

Perkinsus olseni in green-lipped mussels Perna canaliculus: diagnostic evaluation, prevalence, and distribution.

Perkinsus olseni (Perkinsidae) is a molluscan parasite notifiable to the World Organisation for Animal Health that is reported in several shellfish hosts in New Zealand, including the native green-lipped mussel Perna canaliculus. Green-lipped mussels comprise over half of New Zealand's aquaculture export value and have historically been considered free of serious diseases based on extensive histology-based surveillance. The discovery of P. olseni in green-lipped mussels has raised questions about future disease threats to green-lipped mussels, particularly under changing ocean climatic conditions. Using mussels collected from farmed (n = 358) and wild (n = 236) populations, we aimed to determine the distribution and prevalence of P. olseni in green-lipped mussels around New Zealand, and assess the performance of diagnostic tests, including real-time PCR, conventional PCR, and culture using Ray's fluid thioglycolate medium (RFTM). Prevalence and diagnostic test performance was evaluated using Bayesian latent class analysis with informative priors. The prevalence of P. olseni was 0-3%, except for 1 wild population from a harbour where prevalence was 22%. Real-time PCR had the highest diagnostic sensitivity (87%) compared to 62 and 21% for conventional PCR and RFTM, respectively. Diagnostic specificity was similar among all methods (96-98%). No mortality was observed during the study. Our results suggest that real-time PCR is the diagnostic test best suited for surveillance of P. olseni in subclinically infected green-lipped mussels under New Zealand conditions.

Isolation and structural characterization of bioactive glycosaminoglycans from the green-lipped mussel Perna canaliculus

Chondroitin sulfate (CS) and heparan sulfate (HS) are sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide units composed of hexosamine and hexuronic acid. GAG chains exhibit diverse bioactivities in a structure-specific manner. Marine invertebrates are a rich source of highly sulfated and rare structures of GAG chains. Here, we isolated GAGs from the green-lipped mussel Perna canaliculus, an aquaculture species that is produced on a large scale. We separated GAGs based on the degree of negative charges and analyzed their disaccharide compositions. CS and HS both exhibited characteristic compositions of differently sulfated disaccharides. CS chains showed a higher degree of sulfation than HS chains and contained a high percentage of the E unit disaccharide GlcA-GalNAc(4,6-O-disulfate). Furthermore, CS chains rich in the E unit stimulated the neurite outgrowth of primary cultured neurons. The present results indicate the potential of P. canaliculus GAGs as biomaterials to study the structure-function relationships of GAGs.

Integrating Animal Health and Stress Assessment Tools Using the Green-Lipped Mussel Perna canaliculus as a Case Study

Marine organisms are constantly exposed to stress, such as changes in seawater temperature, which may elicit biochemical, molecular, and physiological changes. In the present study, an integrative approach to evaluate stress in the green-lipped mussel Perna canaliculus exposed to control, moderate, and severe heat stress was used. Flow cytometry (FCM) was used to measure hemolymph parameters, including hemocyte concentration, viability, and reactive oxygen species (ROS) production. Spectrophotometry and a handheld electrochemical meter were used to determine the total antioxidant capacity (TAC) of hemolymph and gill tissue, and metabolomics was used to contrast specific metabolic responses among treatments. For hemolymph parameters measured using FCM, the number of nonviable hemocytes increased with the severity of heat shock. The proportion of superoxide-positive hemocytes mirrored the increase in nonviability; by contrast, the general ROS production initially increased following moderate heat shock, but then decreased after severe heat shock. Trolox-equivalent antioxidant capacity in the gill tissue and fast-acting antioxidant levels in the haemolymph showed small but significant decreases following heat shock, whereas the reciprocal pattern was seen for slow-acting and TAC in the hemolymph. Metabolomic profiles discriminated between treatments, with energy metabolism pathways appearing the most affected. The approach used in this study provides a deeper mechanistic understanding of the stress responses of organisms exposed to heat stress; however, these analytical techniques may be combined or used independently to measure stress in marine organisms in the laboratory or in the field, which can improve health assessments of wild and farmed aquatic organisms.

Environmental predictors of sediment denitrification rates within restored green-lipped mussel Perna canaliculus beds

Benthic processes in coastal marine environments can enhance the natural removal of bioreactive nitrogen through denitrification (DNF), a valuable ecosystem service as nutrient over-enrichment intensifies globally. Enhancing ecosystem services is an important justification for restoring coastal ecosystems, and while it is known that epifaunal bivalves (oysters or mussels) are capable of influencing nitrogen cycling, empirical measurement of the role of particular species across a range of environmental conditions is missing. Bivalves within shellfish beds are not uniformly distributed and thus clumps and empty patches within restored beds may differentially impact DNF given the importance of local biogeochemistry. This study reports DNF and respiration rates in 4 restored beds that vary in sediment composition, while identifying which ecological and biogeochemical factors best explain the observed variability in measured fluxes. We deployed benthic chambers in sediments with and without mussels at these sites, and measured net N2 fluxes through membrane inlet mass spectroscopy. Sediment organic matter proved to be the most significant predictor of DNF rates in regression tree and random forest models, suggesting that biodeposition by green-lipped mussels enhances nitrogen removal at these sites and that these effects occur across beds despite differences in mussel density. Greatest DNF rates corresponded to lower sediment chlorophyll a concentrations and higher nitrate/nitrite effluxes measured within chambers. Determining the influence of subtidal mussel restoration on significant sediment processes informs future restoration efforts aiming to maximise this nitrogen removal service, while providing insights on underrepresented oligotrophic systems of the southern hemisphere.

Stress-on-stress responses of a marine mussel, Perna canaliculus: food limitation reduces the ability to cope with heat stress in juveniles

The marine environment is ever-changing, with daily and seasonal variations in factors such as food availability and seawater temperature. These stressors can affect physiological processes in aquatic organisms, resulting in sub-lethal or lethal consequences. This study assessed the effects of food limitation (i.e. fasting) on heat-stress responses in juveniles (~1.3 mm in shell length) of the green-lipped musselPerna canaliculus. Fasting for up to 24 h did not have a significant effect on oxidative damage (protein carbonyls and lipid hydroperoxide accumulation) or the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) after exposure to heat stress. However, fasting for 54 h and subsequent heat stress resulted in increased oxidative damage and decreased activity of antioxidant enzymes in juvenile mussels. Gene expression of 70 kDa heat shock protein (hsp70) was only significantly affected by heat shock, not nutritional status. Tissue carbohydrate and protein levels were significantly depleted by 54 h of fasting; as these proximate components represent key energy substrates for bivalves, it is suggested that energy limitation contributes to compromised antioxidant activity and predisposition to oxidative damage.

Microplastics in the New Zealand green lipped mussel Perna canaliculus

Abstract Microplastics are increasingly being recognised as a potential threat to New Zealand's coastal waters, however there is limited data on abundance of microplastics in marine organisms for New Zealand. Microplastic ingestion by the iconic green-lipped mussel Perna canaliculus was assessed. Microplastics were found in Perna canaliculus from 6 out of 9 locations sampled at abundances ranging from 0 to 1.5 particles per mussel and tissue microplastic concentrations ranged from 0 to 0.48 particles g tissue -1 (wet wt). The microplastics ranged in size from 50 to 700 μm with a median diameter of 100 μm. Polyethylene was the most frequently detected polymer with fragments the most common morphotype. These results indicate that microplastics are widespread in New Zealand's coastal waters and further assessment of microplastic contamination of New Zealand coastal environments and biota is warranted.

Effects of stock origin and environment on growth and reproduction of the green-lipped mussel Perna canaliculus

The effect of stock origin and growing environment on growth and reproduction of the green-lipped mussel Perna canaliculus was investigated on the marine farms in the Marlborough Sounds, New Zealand. Following the normal commercial practice, mussel stocks from three widely separated origins in New Zealand were transplanted to six sites in Marlborough Sounds and grown on ropes hung from commercial longlines for eleven months. Stock origin had significant effects on growth rates as measured by shell length and flesh weight. Growing sites also showed a significant effect on flesh growth rate but only a small effect on shell length growth, with considerable variation among sites. Two sites (Beatrix Bay and Hallam Cove) had the fastest growth in flesh weight. One stock (Golden Bay) showed the fastest growth and lowest mid-winter reproductive rates, while the Kaitaia stock (the most commonly used one in industry) showed highest winter reproductive rate. Spawning was responsible for mid-winter declines in flesh weight among all stocks, but the Golden Bay stock recovered flesh weight more rapidly than other stocks after spawning. The stock differences in growth suggest that genetic traits of stock origin remained after mussels were grown in different environments (sites). In addition, we speculate that there would be a large variation of physiological rates between stocks including filtration, ingestion and respiration rates. The variation in growth and reproduction suggests that there would be a significant difference in energy allocation for reproduction, flesh and shell growth among stocks. The study has obvious application to the mussel industry for planning and selective seeding of stocks to maximise economic benefits. The use of fast-growing stocks and timing of harvesting in mid-winter can dramatically improve quality and quantity of production.

Physiological basis of inter-population, inter-familiar and intra-familiar differences in growth rate in the green-lipped mussel Perna canaliculus

In New Zealand, three quarters (by value) of national aquaculture exports are based on the production of an endemic species, the green-lipped mussel, Perna canaliculus, yet there remains a paucity of information describing its underpinning biology. The majority of seed stock is still derived from wild capture from two main geographic locations, however commercial hatchery production has just begun. An established selective breeding programme, now in its 7th generation, has created family lines selected for desirable production traits, including growth rate. The current study therefore used animals derived from selectively bred lines, as well as animals produced in the hatchery from the two geographically distant populations used for commercial spat-catching, which are observed to have differences in growth rates, to explore the key energetic and morphological parameters that may determine fast and slow growth and growth efficiency. Metabolic rates, clearance and assimilation parameters, and morphological characteristics were established for mussels from 3 distinct levels of relatedness; comparing populations, full sib families (selected a priori for fast or slow growth rate), and inter-individual differences between siblings within families displaying heterogeneous growth rates.Scaling parameters were also determined for metabolic rate, clearance rate, and gill-surface area in the two wild populations of mussels, for comparison of the allometry of the populations, and for size standardization of data. No significant inter-population differences were found in the scaling exponent for any of the parameters, indicating that the size-dependency of physiological rates was effectively the same for mussels from the different geographic areas. However, in contrast, significantly different mass-specific clearance rates were seen in mussels from the two different populations, indicating enhanced energy balances for mussels derived from the Golden Bay population. In the inter- and intra-family experiments, significant differences were found between fast-growing and slow-growing mussels both in terms of anatomy (condition index and relative size of the digestive gland), and in physiological traits such as clearance rate, routine metabolic rate, scope for growth, growth efficiency and metabolic costs of feeding and growth. These results point towards a relatively higher food processing capacity in the gut of faster-growing mussels, and a generally higher metabolic cost of feeding and growth in slower growing mussels. Overall these results reveal the strength of the genetic factors in determining inter-individual variations in physiological performance affecting growth potential, and reinforce the notion that selection of breeding stock both with regard to origin or family provides considerable scope for improvement in mussel production.

Highly ordered nano-scale structure in nacre of green-lipped mussel Perna canaliculus

The ability of the complex hierarchical structure of nacre to withstand huge work of fracture beyond its constituent materials has generated much interest in its growth mechanism and biomimicry studies. However, the structural features directly involved in the robust mechanical properties have not been successfully identified or emulate in biomimetic materials. In the current article, we present the characterisation of a novel nanostructure framework in nacre of Perna canaliculus after chemical etching. The inner structure of the nacre platelet reveals a crystalline three-dimensional framework of orientated fibrous aragonite crystals, which shows that the hierarchical structure at the nano-scale level is much more complex than researchers previously thought. Fracture analysis shows that the fibrous aragonite framework remains largely intact, which indicates the strengthening nature of the elusive internal structure. The discovery of the nano-scale highly ordered structure could be the key to understanding the toughening mechanism in nacre and could serve as a guide to the future biomimetic design of nacre-like, high strength, tough, composite materials.

Response to "Acute Hepatitis Induced by Lyprinol, the Lipid Extract of the Green-Lipped Mussel (Perna canaliculus), in a Patient with Polyarthrosis".

The title of the case report “Acute hepatitis induced by lyprinol, the lipid extract of the green-lipped mussel (Perna canaliculus), in a patient with polyarthrosis” [1] asserts a definitive causal relationship between Lyprinol and acute hepatitis. We are concerned that the report itself does not provide evidence that supports a definitive or highly probable association. As no rechallenge was undertaken definitive causality is impossible to prove.

Erratum to: A randomized controlled trial investigating the effects of PCSO-524®, a patented oil extract of the New Zealand Green Lipped Mussel (Perna canaliculus), on the behaviour, mood, cognition and neurophysiology of children and adolescents (aged 6–14 years) experiencing clinical and sub-clinical levels of hyperactivity and inattention: study protocol ACTRN12610000978066

Erratum to: A randomized controlled trial investigating the effects of PCSO-524®, a patented oil extract of the New Zealand Green Lipped Mussel (Perna canaliculus), on the behaviour, mood, cognition and neurophysiology of children and adolescents (aged 6–14 years) experiencing clinical and sub-clinical levels of hyperactivity and inattention: study protocol ACTRN12610000978066

Biological characteristics of parasitic Nepinnotheres novaezelandiae within a Perna canaliculus farm

Pea crabs are commercially significant parasites in the aquaculture production of bivalves in many parts of the world. However, there is scant information available on the biology of these important parasites in aquaculture. The population structure, sex ratio, and breeding status were determined for the pea crab Nepinnotheres novaezelandiae residing in a typical green-lipped mussel Perna canaliculus farm in New Zealand. Of the 324 crabs randomly sampled, there were significantly more female (82.4%) than male (17.6%) crabs found. The vast majority of crabs (87.0%) were sexually mature and of these, females comprised 86.4% and males 13.6%. However, the sex ratio of immature crabs was relatively even, suggesting that male crabs may have higher mortality while searching for mates. Crab size was highly variable, indicating that recruitment to mussels in the farm was continuous. Carapace width ranged from 4.00 to 11.5 mm, with males tending to be smaller with a mean (±SE) carapace width of 6.31 ± 0.16 mm versus females with a carapace width of 8.03 ± 0.06 mm. The crabs did not show any preference for parasitizing mussels of different sexes. Despite the fact that the mussels were only 10 mo old, most female crabs were sexually mature (Stage V) and 89.3% were gravid. The mean (±SE) clutch size was 2592 ± 579 and clutch size was directly associated with female carapace width. The mussel farm pea crab population was estimated at 126390 ± 14144 individuals, including 93000 gravid females carrying a total of over 241 million eggs. Overall, the results show that pea crabs rapidly colonize farmed mussels and mature quickly to establish a significant breeding population within the mussel farm, with larval output capable of infecting nearby mussel farms as well as wild populations of bivalves.

Acute Hepatitis Induced by Lyprinol, the Lipid Extract of the Green-Lipped Mussel (Perna canaliculus), in a Patient with Polyarthrosis.

Lyprinol, the lipid extract of the green-lipped mussel (Perna canaliculus), is a readily and freely available agent with a putative anti-inflammatory impact. It has already found application as a complementary and supplementary treatment of osteoarthritis, rheumatoid arthritis, asthma, and cancer. So far no major side effects for Lyprinol have been reported, yet. Here, we present the case of a 76-year-old woman with acutely exacerbating abdominal pain and highly elevated liver transaminases while taking Lyprinol as a complementary treatment of polyarthrosis.

Latitudinal comparison of thermotolerance and HSP70 production in F2 larvae of the Greenshell mussel (Perna canaliculus)

We report the first measures of thermotolerance (recorded as percentage mortality and induced HSP70 production) for pelagic larvae of three populations of the New Zealand greenshell (green-lipped) mussel Perna canaliculus. Our goal was to determine whether distinct populations of P. canaliculus were more susceptible to predicted climate change than others, and whether such patterns of susceptibility were either genetically controlled (local adaptation of populations) or simply reflect the acclimatory capacity of this species. F2 larvae from three P. canaliculus populations (D'Urville Island, Banks Peninsula and Stewart Island) were subjected to an acute thermal challenge (3 h exposure to a fixed temperature in the range 20-42°C). No latitudinal patterns in either percentage mortality or HSP70 protein production were apparent. For all populations, larval mortality (LT50) was between 32.9 and 33.9°C, with significant amounts of HSP70 induction only occurring in those individuals that experienced temperatures of 40°C or greater. The data presented therefore do not support the hypothesis that genetic adaptation of P. canaliculus to distinct thermal environments will be reflected by a corresponding difference in acute heat tolerance. In fact, the apparently vulnerable veligers show a surprisingly wide thermal safety margin. To develop a comprehensive understanding of the effects of ocean warming upon this species, subsequent studies should consider the impacts of sub-lethal stress upon fitness in addition to chronic thermal challenge and, crucially, the response of sedentary juvenile and adult stages.

A Novel Method for Determining the Nutritional Condition of Seed Green-Lipped Mussels,Perna canaliculus

Poor nutritional condition of seed of the green-lipped mussel Perna canaliculus (Gmelin 1791) is a major cause of significant losses after seeding out onto mussel farms. Biochemical analysis of experimentally unfed seed mussels showed they preferentially depleted glycogen reserves versus lipid and protein during short periods of starvation (≤8 days). This knowledge allowed the use of a human diabetic glucose meter to assess quickly the levels of glycogen in seed mussels after they were first homogenized and then digested with α-amylase, which converted the glycogen to glucose and maltose. The assay was sensitive enough to detect significant differences between mussels that had been continuously fed (6.04 ± 0.24 (SE) mmol/L) compared with mussels that had been unfed for 4 days (1.71 ± 0.06 mmol/L) or 8 days (0.67 ± 0.02 mmol/L). These results were consistent with biochemical analysis of the actual glycogen content of the experimental groups (16.6 ± 1.8 mg/g dry mass vs. 6.2 ± 1.0 mg/g and 5.5 ± 0.7 mg/g, respectively). This novel assay has the potential for quickly assessing the nutritional quality of seed mussels, enabling the reduction of losses of seed in the mussel farming industry.

An Evidence-Based Systematic Review of Green-Lipped Mussel (Perna canaliculus) by the Natural Standard Research Collaboration

This paper is an evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. Search strategy. To prepare each Natural Standard review, electronic searches are conducted in nine databases, including AMED, CANCERLIT, CINAHL, CISCOM, the Cochrane Library, EMBASE, HerbMed, International Pharmaceutical s, Medline, and NAPRALERT. Search terms include the common name(s), scientific name(s), and all listed synonyms for each topic. Hand searches are conducted of 20 additional journals (not indexed in common databases), and of bibliographies from 50 selected secondary references. No restrictions are placed on language or quality of publications. Researchers in the field of complementary and alternative medicine (CAM) are consulted for access to additional references or ongoing research. Selection Criteria. All literature is collected pertaining to efficacy in humans (regardless of study design, quality, or language), dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanism of action (in vitro, animal research, human data). Standardized inclusion/exclusion criteria are utilized for selection. Data Analysis. Data extraction and analysis are performed by healthcare professionals conducting clinical work and/or research at academic centers, using standardized instruments that pertain to each review section (defining inclusion/exclusion criteria and analytic techniques, including validated measures of study quality). Data are verified by a second reviewer. Review Process. A blinded review is conducted by multidisciplinary research-clinical faculty at major academic centers with expertise in epidemiology and biostatistics, pharmacology, toxicology, CAM research, and clinical practice. In cases of editorial disagreement, a three-member panel of the Editorial Board addresses conflicts, and consults experts when applicable. Authors of studies are contacted when clarification is required.

Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus

BackgroundRheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel Perna canaliculus (Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses.MethodsIn our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes in vitro with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent in vivo experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators.ResultsFollowing LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-α and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001–1 μM. We also demonstrate that in vitro neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner.ConclusionThese data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.