Benson K.F.,NIS Labs |
Redman K.A.,NIS Labs |
Carter S.G.,NIS Labs |
Keller D.,Ganeden Biotech |
And 3 more authors.
World Journal of Gastroenterology | Year: 2012
AIM: To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells. METHODS: Ganeden Bacillus coagulans 30 (GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite (MET) fraction. A second fraction was made to generate a crude cell-wall-enriched fraction, by centrifugation and lysis, followed by washing. A preparation of MET was subjected to size exclusion centrifugation, generating three fractions: < 3 kDa, 3-30 kDa, and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell (PBMC) as a source of antigen-presenting mononuclear phagocytes. The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14, CD16, CD80 and CD86 and analyzed by flow cytometry. RESULTS: Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes. The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells, and this property was associated with the high molecular weight metabolite fraction. Changes were also seen for the dendritic cell maturation markers CD80 and CD86. On CD14dim cells, an increase in both CD80 and CD86 expression was seen, in contrast to a selective increase in CD86 expression on CD14 bright cells. The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation. The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells. CONCLUSION: The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells, important for immunological decision-making. © 2012 Baishideng. All rights reserved.
Schauss A.G.,Meridian Life Sciences, Inc.
Journal of Orthomolecular Medicine | Year: 2012
Heroin addiction is a serious health and social problem that afflicts societies around the world. Its addicting characteristics have been known for thousands of years. Derived from opium, obtained from the opium poppy (Papaver somniferum), heroin is highly addictive. Conventional approaches to heroin withdrawal involve the use of synthetic or semi-synthetic opioids, with or without concomitant behavioral therapy. A study conducted in New York City in the 1960s, demonstrated that by giving increasing doses of vitamin C (ascorbic acid) salts administered orally in water or juice during withdrawal, vitamin C blocked opioid receptors in the brain, and attenuated withdrawal symptoms, encouraging heroin addicts to end their dependence on heroin. A 19 78 field visit to Seattle, Washington, by officials of the National Institute for Drug Abuse and Alcoholism (NIDAA) at the U.S. National Institutes for Health (NIH), confirmed its effectiveness, yet the agency to date has failed to provide funding to support further research on this promising treatment modality. Despite serious reported side effects, pharmacotherapeutic approaches in the treatment of heroin-dependence prevail with support by NIDAA, while nutrient-based therapies, that could help break the cycle of addiction, are disregarded.
Raman J.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases |
Raman J.,National Health Research Institute |
Guan Y.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases |
Guan Y.,U.S. National Institutes of Health |
And 5 more authors.
Glycobiology | Year: 2012
The formation of mucin-type O-glycans is initiated by an evolutionarily conserved family of enzymes, the UDP-N-acetyl α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). The human genome encodes 20 transferases; 17 of which have been characterized functionally. The complexity of the GalNAc-T family reflects the differential patterns of expression among the individual enzyme isoforms and the unique substrate specificities which are required to form the dense arrays of glycans that are essential for mucin function. We report the expression patterns and enzymatic activity of the remaining three members of the family and the further characterization of a recently reported isoform, GalNAc-T17. One isoform, GalNAcT-16 that is most homologous to GalNAc-T14, is widely expressed (abundantly in the heart) and has robust polypeptide transferase activity. The second isoform GalNAc-T18, most similar to GalNAc-T8,-T9 and-T19, completes a discrete subfamily of GalNAc-Ts. It is widely expressed and has low, albeit detectable, activity. The final isoform, GalNAc-T20, is most homologous to GalNAc-T11 but lacks a lectin domain and has no detectable transferase activity with the panel of substrates tested. We have also identified and characterized enzymatically active splice variants of GalNAc-T13 that differ in the sequence of their lectin domain. The variants differ in their affinities for glycopeptide substrates. Our findings provide a comprehensive view of the complexities of mucin-type O-glycan formation and provide insight into the underlying mechanisms employed to heavily decorate mucins and mucin-like domains with carbohydrate. © The Author 2012.
Wu X.,University of Arkansas for Medical Sciences |
Wu X.,Hershey Company |
Schauss A.G.,Meridian Life Sciences, Inc.
Journal of Agricultural and Food Chemistry | Year: 2012
Constant overproduction of pro-inflammatory molecules leads to chronic inflammation. Unlike acute inflammation, which is essential for healing, chronic inflammation can delay healing and, if left unchecked, contribute to a host of diseases. There is growing evidence that some dietary factors can play important roles in maintaining health and even reversing the progression of chronic diseases, with anti-inflammatory effects as important underlying mechanism. Such findings add to the body of evidence that certain dietary components, including polyphenols and other types of compounds, found in various dietary factors including fruits, berries, vegetables, nuts, whole grains, and foods of marine origin, can play an important role in attenuating and mitigating chronic pro-inflammatory processes associated with chronic diseases. © 2012 American Chemical Society.
Endres J.R.,Meridian Life Sciences, Inc. |
Qureshi I.,Meridian Life Sciences, Inc. |
Farber T.,Toxicology Advisory Services |
Hauswirth J.,Van Gemert and Hauswirth LLC |
And 3 more authors.
Food and Chemical Toxicology | Year: 2011
Some strains of Bacillus coagulans can survive extremes of heat, stomach acid and bile acids, to which commonly consumed probiotics are susceptible. A toxicological safety assessment was published in 2009 on a proprietary preparation of B. coagulans - GanedenBC30™ - a novel probiotic. It was concluded that GanedenBC30™ is safe for chronic human consumption based upon scientific procedures, supported by a safe history of use (Endres et al., 2009).A one-year chronic oral toxicity study combined with a one-generation reproduction study was conducted to further investigate safety of long-term consumption. The one-year study of GanedenBC30™ administered to male and female HsdBrlHan: Wistar rats in their diet showed no signs of toxicity at the highest dose tested. The conclusion from the reproduction toxicity study is that administration of GanedenBC30™ in the diet caused no signs of toxicity in the parental generation (male or female) nor the F1 offspring. Using the lowest NOEL of 1948mg/kg concluded at the end of the 1-year feeding study, a 100-fold safety factor, a test article concentration of 6.88×1010CFU (colony forming units) per gram, and an average 70kg human, it is determined that GanedenBC30™ is safe for chronic consumption at up to 9.38×1010CFUs per day. © 2011.
Kang J.,University of Arkansas for Medical Sciences |
Thakali K.M.,University of Arkansas for Medical Sciences |
Xie C.,University of Arkansas for Medical Sciences |
Kondo M.,Brunswick Laboratories |
And 6 more authors.
Food Chemistry | Year: 2012
There are two predominant palm tree species producing edible fruit known as "aaí" found widely dispersed through the Amazon: Euterpe oleracea Mart. and Euterpe precatoria Mart. They differ from each other in terms of how the plants grow and their phytochemical composition. E. oleracea (EO) has received considerable attention as a "super fruit" because of its high antioxidant capacity, while studies on E. precatoria (EP) remain rare. In this study, the antioxidant and anti-inflammatory activities of EP fruit pulps were evaluated by different assays including a series of oxygen radical absorbance capacity (ORAC) based assays, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the cell-based antioxidant protection in erythrocyte (CAP-e) assay, as well as the nuclear factor-kappa B (NF-κB) secreted embryonic alkaline phosphatase (SEAP) assay. Total phenolics were also measured as an indication of the total phenol content. For comparative purposes, the EO fruit pulp was included. The antioxidant capacity of the EP fruit pulp was determined to be superior to the EO fruit pulp in every chemical based assay. In the cell-based CAP-e assay, the EP fruit pulp showed a dose-dependent inhibition against oxidative damage with an IC 50 of 0.167 g/l. In the SEAP reporter assay, the EP fruit pulp polyphenol-rich extracts inhibited lipopolysaccharide (LPS)-induced NF-κB activation by 23% (p < 0.05) at 20 μg/ml, whereas the extract of the EO fruit pulp did not show a significant inhibitory effect at comparable doses. In addition, carotenoids were quantified for the first time in EP, since EP has high scavenging capacity against singlet oxygen. © 2012 Elsevier Ltd. All rights reserved.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2013
Rotavirus is the most common cause of debilitating diarrhea, dehydration and death in infants and young children around the globe. Currently approved live oral vaccines (Rotarix® and RotaTeq®) are only -50% or less effective in children from developing countries. This reduced efficacy is due to factors that decrease the effective titer of the virus reaching the gut, impairment of the host response of the infant and/or differences in virus and serotype distribution. In addition, both vaccines are associated with a low risk of diarrhea and intussusception among infants who receive the vaccine. It is critical that alternative approaches for a rotavirus vaccine be considered to improve the safety and efficacy of oral rotavirus vaccines. Rotavirus strain CDC-9 developed by the CDC is a viable vaccine candidate based on desirable patterns of potential attenuation, robust growth in cGMP qualified Vero cells, and proof of concept in pre-clinical studies. In this Phase I proposal, Meridian Life Science, Inc. will identify growth kinetics of the virus and develop robust downstream purification and heat-inactivation processes. The work described in this proposal will provide the framework for manufacture of clinical grade material for Phase I and Phase II human clinical trials.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.14M | Year: 2014
To improve the safety and efficacy of oral rotavirus vaccines, CDC scientists have developed a proprietary inactivated rotavirus vaccine (IRV) technology (new human strains and a novel method for rotavirus inactivation) and demonstrated the immunogenicity in mice  and protective efficacy in piglets  of this IRV by intramuscular (IM) administration. More recently, CDC scientists have demonstrated enhanced immunogenicity of IRV using an innovative microneedle patch technology, achieving comparable antibody titers with a 1/10th of the antigen dose compared to those induced by a full IM dose of vaccine. Microneedles provide a simple and painless method to administer vaccines without using hypodermic needles. They are inexpensive to manufacture and may not require a cold chain for storage and transport, a major advantage for immunization campaigns in the developing world. With the establishment of proof of concept for IM and skin immunization in animals, CDC has entered an agreement with Meridian Life Science (MLS) to produce a master virus bank (MVB) under Good Manufacturing Practice (GMP) conditions at the MLS facilities in Memphis, Tennessee. Based on the results and progress from the Phase I SBIR contract, the phase II contract will focus on preparation of inactivated rotavirus vaccine pilot lots for phase I clinical trials.
PubMed | University of West of Scotland, Meridian Life Sciences, Inc. and University of Strathclyde
Type: | Journal: Drug and alcohol dependence | Year: 2016
Availability of the opioid antagonist naloxone for lay administration has grown substantially since first proposed in 1996. Gaps remain, though, in our understanding of how people who inject drugs (PWID) engage with naloxone programmes over time.This paper aimed to address three specific evidence gaps: the extent of naloxone supply to PWID; supply-source (community or prisons); and the carriage of naloxone among PWID.Analysis of Scotlands Needle Exchange Surveillance Initiative (NESI) responses in 2011-2012 and 2013-2014 was undertaken with a specific focus on the extent of Scotlands naloxone supply to PWID; including by source (community or prisons); and on the carriage of naloxone. Differences in responses between the two surveys were measured using Chi-square tests together with 95% confidence intervals for rate-differences over time.The proportion of NESI participants who reported that they had been prescribed naloxone within the last year increased significantly from 8% (175/2146; 95% CI: 7-9%) in 2011-2012 to 32% (745/2331; 95% CI: 30% to 34%) in 2013-2014. In contrast, the proportion of NESI participants who carried naloxone with them on the day they were interviewed decreased significantly from 16% (27/169; 95% CI: 10% to 22%) in 2011-2012 to 5% (39/741; 95% CI: 4% to 7%) in 2013-2014.The supply of naloxone to PWID has increased significantly since the introduction of a National Naloxone Programme in Scotland in January 2011. In contrast, naloxone carriage is low and decreased between the two NESI surveys; this area requires further investigation.
Meridian Life Sciences, Inc. | Date: 2012-03-13
biochemicals, namely, reagents, assays, antigens and antibodies for diagnostic use in scientific and medical laboratory research and diagnostics.